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Prognostic Value of the Expression of p53 and bcl-2 in Non-Small Cell Lung Cancer (비소세포폐암에서 p53과 bcl-2의 발현이 예후에 미치는 영향)

  • Yang, Seok-Chul;Yoon, Ho-Joo;Shin, Dong-Ho;Park, Sung-Soo;Lee, Jung-Hee;Keum, Joo-Seob;Kong, Gu;Lee, Jung-Dal
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.5
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    • pp.962-974
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    • 1998
  • Background: Alteration of p53 tumor suppressor genes is most frequently identified in human neoplasms, including lung carcinoma. It is well known that bcl-2 oncoprotein protects cells from apoptosis. Recent studies have demonstrated that bcl-2 expression is associated with favorable prognosis for patients with non-small cell lung carcinoma. However, the precise biologic role of bcl-2 in the development of these tumors is still obscure. p53 and bcl-2 have important regulatory influence in the apoptotic pathway and thus their relationship is of interest in tumorigenesis, especially lung cancer. Purpose: The author investigated to know the prognostic significance of the expression of p53 and bcl-2 in radically resected non-small cell lung cancer. Method: 84 cases of formalin-fixed paraffin-embedded blocks from resected primary non-small cell lung cancer from 1980 to 1994 at Hanyang University Hospital were available for both clinical follow-up and immunohistochemical staining using monoclonal antibodies for p53 and bcl-2. Results : The histologic classification of the tumor was based on WHO criteria., and the specimens included 45 squamous cell carcinomas(53.6%), 28 adeonocarcinomas(33.3%) and 11 large cell carcinomas(13.1 %). p53 immunoreactivity was noted in 47 cases of 84 cases(56.0%). bcl-2 immunoreactivity was noted in 15 cases of 84 cases(17.9%). The mean survival duration was $64.23{\pm}10.73$ months in bcl-2 positive group and $35.28{\pm}4$. 39 months in bcl-2 negative group. The bcl-2 expression was significantly correlated with survival in radically resected non-small cell lung cancer patients(p=0.03). The mean survival duration was $34.71{\pm}6.12$ months in p53 positive group and $45.35{\pm}6.30$ months in p53 negative group(p=0.21). The p53 expression was not predictive for survival. There was no correlation between combination of the different status of p53 and bcl-2 expression in our study. Conclusions : The interaction and the regulation of new biologic markers, such as those involved in the apoptotic pathway, are complex. bcl-2 overexpression is a good prognostic factor in non-small cell lung cancer and p53 expression is not significantly associated with the prognostic factor in non-small cell lung cancer.

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A Study on Developing a VKOSPI Forecasting Model via GARCH Class Models for Intelligent Volatility Trading Systems (지능형 변동성트레이딩시스템개발을 위한 GARCH 모형을 통한 VKOSPI 예측모형 개발에 관한 연구)

  • Kim, Sun-Woong
    • Journal of Intelligence and Information Systems
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    • v.16 no.2
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    • pp.19-32
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    • 2010
  • Volatility plays a central role in both academic and practical applications, especially in pricing financial derivative products and trading volatility strategies. This study presents a novel mechanism based on generalized autoregressive conditional heteroskedasticity (GARCH) models that is able to enhance the performance of intelligent volatility trading systems by predicting Korean stock market volatility more accurately. In particular, we embedded the concept of the volatility asymmetry documented widely in the literature into our model. The newly developed Korean stock market volatility index of KOSPI 200, VKOSPI, is used as a volatility proxy. It is the price of a linear portfolio of the KOSPI 200 index options and measures the effect of the expectations of dealers and option traders on stock market volatility for 30 calendar days. The KOSPI 200 index options market started in 1997 and has become the most actively traded market in the world. Its trading volume is more than 10 million contracts a day and records the highest of all the stock index option markets. Therefore, analyzing the VKOSPI has great importance in understanding volatility inherent in option prices and can afford some trading ideas for futures and option dealers. Use of the VKOSPI as volatility proxy avoids statistical estimation problems associated with other measures of volatility since the VKOSPI is model-free expected volatility of market participants calculated directly from the transacted option prices. This study estimates the symmetric and asymmetric GARCH models for the KOSPI 200 index from January 2003 to December 2006 by the maximum likelihood procedure. Asymmetric GARCH models include GJR-GARCH model of Glosten, Jagannathan and Runke, exponential GARCH model of Nelson and power autoregressive conditional heteroskedasticity (ARCH) of Ding, Granger and Engle. Symmetric GARCH model indicates basic GARCH (1, 1). Tomorrow's forecasted value and change direction of stock market volatility are obtained by recursive GARCH specifications from January 2007 to December 2009 and are compared with the VKOSPI. Empirical results indicate that negative unanticipated returns increase volatility more than positive return shocks of equal magnitude decrease volatility, indicating the existence of volatility asymmetry in the Korean stock market. The point value and change direction of tomorrow VKOSPI are estimated and forecasted by GARCH models. Volatility trading system is developed using the forecasted change direction of the VKOSPI, that is, if tomorrow VKOSPI is expected to rise, a long straddle or strangle position is established. A short straddle or strangle position is taken if VKOSPI is expected to fall tomorrow. Total profit is calculated as the cumulative sum of the VKOSPI percentage change. If forecasted direction is correct, the absolute value of the VKOSPI percentage changes is added to trading profit. It is subtracted from the trading profit if forecasted direction is not correct. For the in-sample period, the power ARCH model best fits in a statistical metric, Mean Squared Prediction Error (MSPE), and the exponential GARCH model shows the highest Mean Correct Prediction (MCP). The power ARCH model best fits also for the out-of-sample period and provides the highest probability for the VKOSPI change direction tomorrow. Generally, the power ARCH model shows the best fit for the VKOSPI. All the GARCH models provide trading profits for volatility trading system and the exponential GARCH model shows the best performance, annual profit of 197.56%, during the in-sample period. The GARCH models present trading profits during the out-of-sample period except for the exponential GARCH model. During the out-of-sample period, the power ARCH model shows the largest annual trading profit of 38%. The volatility clustering and asymmetry found in this research are the reflection of volatility non-linearity. This further suggests that combining the asymmetric GARCH models and artificial neural networks can significantly enhance the performance of the suggested volatility trading system, since artificial neural networks have been shown to effectively model nonlinear relationships.

Impact of Semantic Characteristics on Perceived Helpfulness of Online Reviews (온라인 상품평의 내용적 특성이 소비자의 인지된 유용성에 미치는 영향)

  • Park, Yoon-Joo;Kim, Kyoung-jae
    • Journal of Intelligence and Information Systems
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    • v.23 no.3
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    • pp.29-44
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    • 2017
  • In Internet commerce, consumers are heavily influenced by product reviews written by other users who have already purchased the product. However, as the product reviews accumulate, it takes a lot of time and effort for consumers to individually check the massive number of product reviews. Moreover, product reviews that are written carelessly actually inconvenience consumers. Thus many online vendors provide mechanisms to identify reviews that customers perceive as most helpful (Cao et al. 2011; Mudambi and Schuff 2010). For example, some online retailers, such as Amazon.com and TripAdvisor, allow users to rate the helpfulness of each review, and use this feedback information to rank and re-order them. However, many reviews have only a few feedbacks or no feedback at all, thus making it hard to identify their helpfulness. Also, it takes time to accumulate feedbacks, thus the newly authored reviews do not have enough ones. For example, only 20% of the reviews in Amazon Review Dataset (Mcauley and Leskovec, 2013) have more than 5 reviews (Yan et al, 2014). The purpose of this study is to analyze the factors affecting the usefulness of online product reviews and to derive a forecasting model that selectively provides product reviews that can be helpful to consumers. In order to do this, we extracted the various linguistic, psychological, and perceptual elements included in product reviews by using text-mining techniques and identifying the determinants among these elements that affect the usability of product reviews. In particular, considering that the characteristics of the product reviews and determinants of usability for apparel products (which are experiential products) and electronic products (which are search goods) can differ, the characteristics of the product reviews were compared within each product group and the determinants were established for each. This study used 7,498 apparel product reviews and 106,962 electronic product reviews from Amazon.com. In order to understand a review text, we first extract linguistic and psychological characteristics from review texts such as a word count, the level of emotional tone and analytical thinking embedded in review text using widely adopted text analysis software LIWC (Linguistic Inquiry and Word Count). After then, we explore the descriptive statistics of review text for each category and statistically compare their differences using t-test. Lastly, we regression analysis using the data mining software RapidMiner to find out determinant factors. As a result of comparing and analyzing product review characteristics of electronic products and apparel products, it was found that reviewers used more words as well as longer sentences when writing product reviews for electronic products. As for the content characteristics of the product reviews, it was found that these reviews included many analytic words, carried more clout, and related to the cognitive processes (CogProc) more so than the apparel product reviews, in addition to including many words expressing negative emotions (NegEmo). On the other hand, the apparel product reviews included more personal, authentic, positive emotions (PosEmo) and perceptual processes (Percept) compared to the electronic product reviews. Next, we analyzed the determinants toward the usefulness of the product reviews between the two product groups. As a result, it was found that product reviews with high product ratings from reviewers in both product groups that were perceived as being useful contained a larger number of total words, many expressions involving perceptual processes, and fewer negative emotions. In addition, apparel product reviews with a large number of comparative expressions, a low expertise index, and concise content with fewer words in each sentence were perceived to be useful. In the case of electronic product reviews, those that were analytical with a high expertise index, along with containing many authentic expressions, cognitive processes, and positive emotions (PosEmo) were perceived to be useful. These findings are expected to help consumers effectively identify useful product reviews in the future.

KNU Korean Sentiment Lexicon: Bi-LSTM-based Method for Building a Korean Sentiment Lexicon (Bi-LSTM 기반의 한국어 감성사전 구축 방안)

  • Park, Sang-Min;Na, Chul-Won;Choi, Min-Seong;Lee, Da-Hee;On, Byung-Won
    • Journal of Intelligence and Information Systems
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    • v.24 no.4
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    • pp.219-240
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    • 2018
  • Sentiment analysis, which is one of the text mining techniques, is a method for extracting subjective content embedded in text documents. Recently, the sentiment analysis methods have been widely used in many fields. As good examples, data-driven surveys are based on analyzing the subjectivity of text data posted by users and market researches are conducted by analyzing users' review posts to quantify users' reputation on a target product. The basic method of sentiment analysis is to use sentiment dictionary (or lexicon), a list of sentiment vocabularies with positive, neutral, or negative semantics. In general, the meaning of many sentiment words is likely to be different across domains. For example, a sentiment word, 'sad' indicates negative meaning in many fields but a movie. In order to perform accurate sentiment analysis, we need to build the sentiment dictionary for a given domain. However, such a method of building the sentiment lexicon is time-consuming and various sentiment vocabularies are not included without the use of general-purpose sentiment lexicon. In order to address this problem, several studies have been carried out to construct the sentiment lexicon suitable for a specific domain based on 'OPEN HANGUL' and 'SentiWordNet', which are general-purpose sentiment lexicons. However, OPEN HANGUL is no longer being serviced and SentiWordNet does not work well because of language difference in the process of converting Korean word into English word. There are restrictions on the use of such general-purpose sentiment lexicons as seed data for building the sentiment lexicon for a specific domain. In this article, we construct 'KNU Korean Sentiment Lexicon (KNU-KSL)', a new general-purpose Korean sentiment dictionary that is more advanced than existing general-purpose lexicons. The proposed dictionary, which is a list of domain-independent sentiment words such as 'thank you', 'worthy', and 'impressed', is built to quickly construct the sentiment dictionary for a target domain. Especially, it constructs sentiment vocabularies by analyzing the glosses contained in Standard Korean Language Dictionary (SKLD) by the following procedures: First, we propose a sentiment classification model based on Bidirectional Long Short-Term Memory (Bi-LSTM). Second, the proposed deep learning model automatically classifies each of glosses to either positive or negative meaning. Third, positive words and phrases are extracted from the glosses classified as positive meaning, while negative words and phrases are extracted from the glosses classified as negative meaning. Our experimental results show that the average accuracy of the proposed sentiment classification model is up to 89.45%. In addition, the sentiment dictionary is more extended using various external sources including SentiWordNet, SenticNet, Emotional Verbs, and Sentiment Lexicon 0603. Furthermore, we add sentiment information about frequently used coined words and emoticons that are used mainly on the Web. The KNU-KSL contains a total of 14,843 sentiment vocabularies, each of which is one of 1-grams, 2-grams, phrases, and sentence patterns. Unlike existing sentiment dictionaries, it is composed of words that are not affected by particular domains. The recent trend on sentiment analysis is to use deep learning technique without sentiment dictionaries. The importance of developing sentiment dictionaries is declined gradually. However, one of recent studies shows that the words in the sentiment dictionary can be used as features of deep learning models, resulting in the sentiment analysis performed with higher accuracy (Teng, Z., 2016). This result indicates that the sentiment dictionary is used not only for sentiment analysis but also as features of deep learning models for improving accuracy. The proposed dictionary can be used as a basic data for constructing the sentiment lexicon of a particular domain and as features of deep learning models. It is also useful to automatically and quickly build large training sets for deep learning models.

Virtuous Concordance of Yin and Yang and Tai-Ji in Joseon art: Focusing on Daesoon Thought (조선 미술에 내재한 음양합덕과 태극 - 대순사상을 중심으로 -)

  • Hwang, Eui-pil
    • Journal of the Daesoon Academy of Sciences
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    • v.35
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    • pp.217-253
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    • 2020
  • This study analyzes the principles of the 'Earthly Paradise' (仙境, the realm of immortals), 'Virtuous Concordance of Yin and Yang' (陰陽合德), and the 'Reordering Works of Heaven and Earth' (天地公事) while combining them with Joseon art. Therefore, this study aims to discover the context wherein the concept of Taiji in 'Daesoon Truth,' deeply penetrates into Joseon art. Doing so reveals how 'Daesoon Thought' is embedded in the lives and customs of the Korean people. In addition, this study follows a review of the sentiments and intellectual traditions of the Korean people based on 'Daesoon Thought' and creative works. Moreover, 'Daesoon Thought' brings all of this to the forefront in academics and art at the cosmological level. The purpose of this research is to vividly reveal the core of 'Daesoon Thought' as a visual image. Through this, the combination of 'Daesoon Thought' and Joseon art will secure both data and reality at the same time. As part of this, this study deals with the world of 'Daesoon Thought' as a cosmological Taiji principle. This concept is revealed in Joseon art, which is analyzed and examined from the viewpoint of art philosophy. First, as a way to make use of 'Daesoon Thought,' 'Daesoon Truth' was developed and directly applied to Joseon art. In this way, reflections on Korean life within 'Daesoon Thought' can be revealed. In this regard, the selection of Joseon art used in this study highlights creative works that have been deeply ingrained into people's lives. For example, as 'Daesoon Thought' appears to focus on the genre painting, folk painting, and landscape painting of the Joseon Dynasty, attention is given to verifying these cases. This study analyzes 'Daesoon Thought,' which borrows from Joseon art, from the perspective of art philosophy. Accordingly, attempts are made to find examples of the 'Virtuous Concordance of Yin and Yang' and Tai-Ji in Joseon art which became a basis by which 'Daesoon Thought' was communicated to people. In addition, appreciating 'Daesoon Thought' in Joseon art is an opportunity to vividly examine not only the Joseon art style but also the life, consciousness, and mental world of the Korean people. As part of this, Chapter 2 made several findings related to the formation of 'Daesoon Thought.' In Chapter 3, the structures of the ideas of 'Earthly Paradise' and 'Virtuous Concordance of Yin and Yang' were likewise found to have support. And 'The Reordering Works of Heaven and Earth' and Tai-Ji were found in depictions of metaphysical laws. To this end, the laws of 'The Reordering Works of Heaven and Earth' and the structure of Tai-Ji were combined. In chapter 4, we analyzed the 'Daesoon Thought' in the life and work of the Korean people at the level of the convergence of 'Daeesoon Thought' and Joseon art. The analysis of works provides a glimpse into the precise identity of 'Daesoon Thought' as observable in Joseon art, as doing so is useful for generating empirical data. For example, works such as Tai-Jido, Ssanggeum Daemu, Jusachaebujeokdo, Hwajogi Myeonghwabundo, and Gyeongdodo are objects that inspired descriptions of 'Earthly Paradise', 'Virtuous Concordance of Yin and Yang,' and 'The Reordering Works of Heaven and Earth.' As a result, Tai-Ji which appears in 'Daesoon Thought', proved the status of people in Joseon art. Given all of these statements, the Tai-Ji idea pursued by Daesoon Thought is a providence that follows change as all things are mutually created. In other words, it was derived that Tai-Ji ideology sits profoundly in the lives of the Korean people and responds mutually to the providence that converges with 'Mutual Beneficence.'

Estimation of GARCH Models and Performance Analysis of Volatility Trading System using Support Vector Regression (Support Vector Regression을 이용한 GARCH 모형의 추정과 투자전략의 성과분석)

  • Kim, Sun Woong;Choi, Heung Sik
    • Journal of Intelligence and Information Systems
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    • v.23 no.2
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    • pp.107-122
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    • 2017
  • Volatility in the stock market returns is a measure of investment risk. It plays a central role in portfolio optimization, asset pricing and risk management as well as most theoretical financial models. Engle(1982) presented a pioneering paper on the stock market volatility that explains the time-variant characteristics embedded in the stock market return volatility. His model, Autoregressive Conditional Heteroscedasticity (ARCH), was generalized by Bollerslev(1986) as GARCH models. Empirical studies have shown that GARCH models describes well the fat-tailed return distributions and volatility clustering phenomenon appearing in stock prices. The parameters of the GARCH models are generally estimated by the maximum likelihood estimation (MLE) based on the standard normal density. But, since 1987 Black Monday, the stock market prices have become very complex and shown a lot of noisy terms. Recent studies start to apply artificial intelligent approach in estimating the GARCH parameters as a substitute for the MLE. The paper presents SVR-based GARCH process and compares with MLE-based GARCH process to estimate the parameters of GARCH models which are known to well forecast stock market volatility. Kernel functions used in SVR estimation process are linear, polynomial and radial. We analyzed the suggested models with KOSPI 200 Index. This index is constituted by 200 blue chip stocks listed in the Korea Exchange. We sampled KOSPI 200 daily closing values from 2010 to 2015. Sample observations are 1487 days. We used 1187 days to train the suggested GARCH models and the remaining 300 days were used as testing data. First, symmetric and asymmetric GARCH models are estimated by MLE. We forecasted KOSPI 200 Index return volatility and the statistical metric MSE shows better results for the asymmetric GARCH models such as E-GARCH or GJR-GARCH. This is consistent with the documented non-normal return distribution characteristics with fat-tail and leptokurtosis. Compared with MLE estimation process, SVR-based GARCH models outperform the MLE methodology in KOSPI 200 Index return volatility forecasting. Polynomial kernel function shows exceptionally lower forecasting accuracy. We suggested Intelligent Volatility Trading System (IVTS) that utilizes the forecasted volatility results. IVTS entry rules are as follows. If forecasted tomorrow volatility will increase then buy volatility today. If forecasted tomorrow volatility will decrease then sell volatility today. If forecasted volatility direction does not change we hold the existing buy or sell positions. IVTS is assumed to buy and sell historical volatility values. This is somewhat unreal because we cannot trade historical volatility values themselves. But our simulation results are meaningful since the Korea Exchange introduced volatility futures contract that traders can trade since November 2014. The trading systems with SVR-based GARCH models show higher returns than MLE-based GARCH in the testing period. And trading profitable percentages of MLE-based GARCH IVTS models range from 47.5% to 50.0%, trading profitable percentages of SVR-based GARCH IVTS models range from 51.8% to 59.7%. MLE-based symmetric S-GARCH shows +150.2% return and SVR-based symmetric S-GARCH shows +526.4% return. MLE-based asymmetric E-GARCH shows -72% return and SVR-based asymmetric E-GARCH shows +245.6% return. MLE-based asymmetric GJR-GARCH shows -98.7% return and SVR-based asymmetric GJR-GARCH shows +126.3% return. Linear kernel function shows higher trading returns than radial kernel function. Best performance of SVR-based IVTS is +526.4% and that of MLE-based IVTS is +150.2%. SVR-based GARCH IVTS shows higher trading frequency. This study has some limitations. Our models are solely based on SVR. Other artificial intelligence models are needed to search for better performance. We do not consider costs incurred in the trading process including brokerage commissions and slippage costs. IVTS trading performance is unreal since we use historical volatility values as trading objects. The exact forecasting of stock market volatility is essential in the real trading as well as asset pricing models. Further studies on other machine learning-based GARCH models can give better information for the stock market investors.

A Study on Intelligent Value Chain Network System based on Firms' Information (기업정보 기반 지능형 밸류체인 네트워크 시스템에 관한 연구)

  • Sung, Tae-Eung;Kim, Kang-Hoe;Moon, Young-Su;Lee, Ho-Shin
    • Journal of Intelligence and Information Systems
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    • v.24 no.3
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    • pp.67-88
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    • 2018
  • Until recently, as we recognize the significance of sustainable growth and competitiveness of small-and-medium sized enterprises (SMEs), governmental support for tangible resources such as R&D, manpower, funds, etc. has been mainly provided. However, it is also true that the inefficiency of support systems such as underestimated or redundant support has been raised because there exist conflicting policies in terms of appropriateness, effectiveness and efficiency of business support. From the perspective of the government or a company, we believe that due to limited resources of SMEs technology development and capacity enhancement through collaboration with external sources is the basis for creating competitive advantage for companies, and also emphasize value creation activities for it. This is why value chain network analysis is necessary in order to analyze inter-company deal relationships from a series of value chains and visualize results through establishing knowledge ecosystems at the corporate level. There exist Technology Opportunity Discovery (TOD) system that provides information on relevant products or technology status of companies with patents through retrievals over patent, product, or company name, CRETOP and KISLINE which both allow to view company (financial) information and credit information, but there exists no online system that provides a list of similar (competitive) companies based on the analysis of value chain network or information on potential clients or demanders that can have business deals in future. Therefore, we focus on the "Value Chain Network System (VCNS)", a support partner for planning the corporate business strategy developed and managed by KISTI, and investigate the types of embedded network-based analysis modules, databases (D/Bs) to support them, and how to utilize the system efficiently. Further we explore the function of network visualization in intelligent value chain analysis system which becomes the core information to understand industrial structure ystem and to develop a company's new product development. In order for a company to have the competitive superiority over other companies, it is necessary to identify who are the competitors with patents or products currently being produced, and searching for similar companies or competitors by each type of industry is the key to securing competitiveness in the commercialization of the target company. In addition, transaction information, which becomes business activity between companies, plays an important role in providing information regarding potential customers when both parties enter similar fields together. Identifying a competitor at the enterprise or industry level by using a network map based on such inter-company sales information can be implemented as a core module of value chain analysis. The Value Chain Network System (VCNS) combines the concepts of value chain and industrial structure analysis with corporate information simply collected to date, so that it can grasp not only the market competition situation of individual companies but also the value chain relationship of a specific industry. Especially, it can be useful as an information analysis tool at the corporate level such as identification of industry structure, identification of competitor trends, analysis of competitors, locating suppliers (sellers) and demanders (buyers), industry trends by item, finding promising items, finding new entrants, finding core companies and items by value chain, and recognizing the patents with corresponding companies, etc. In addition, based on the objectivity and reliability of the analysis results from transaction deals information and financial data, it is expected that value chain network system will be utilized for various purposes such as information support for business evaluation, R&D decision support and mid-term or short-term demand forecasting, in particular to more than 15,000 member companies in Korea, employees in R&D service sectors government-funded research institutes and public organizations. In order to strengthen business competitiveness of companies, technology, patent and market information have been provided so far mainly by government agencies and private research-and-development service companies. This service has been presented in frames of patent analysis (mainly for rating, quantitative analysis) or market analysis (for market prediction and demand forecasting based on market reports). However, there was a limitation to solving the lack of information, which is one of the difficulties that firms in Korea often face in the stage of commercialization. In particular, it is much more difficult to obtain information about competitors and potential candidates. In this study, the real-time value chain analysis and visualization service module based on the proposed network map and the data in hands is compared with the expected market share, estimated sales volume, contact information (which implies potential suppliers for raw material / parts, and potential demanders for complete products / modules). In future research, we intend to carry out the in-depth research for further investigating the indices of competitive factors through participation of research subjects and newly developing competitive indices for competitors or substitute items, and to additively promoting with data mining techniques and algorithms for improving the performance of VCNS.

Correlation of p53 Protein Overexpression, Gene Mutation with Prognosis in Resected Non-Small Cell Lung Cancer(NSCLC) Patients (비소세포폐암에서 p53유전자의 구조적 이상 및 단백질 발현이 예후에 미치는 영향)

  • Lee, Y.H.;Shin, D.H.;Kim, J.H.;Lim, H.Y.;Chung, K.Y.;Yang, W.I.;Kim, S.K.;Chang, J.;Roh, J.K.;Kim, S.K.;Lee, W.Y.;Kim, B.S.;Kim, B.S.
    • Tuberculosis and Respiratory Diseases
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    • v.41 no.4
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    • pp.339-353
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    • 1994
  • Background : The p53 gene codes for a DNA-binding nuclear phosphoprotein that appears to inhibit the progression of cells from the G1 to the S phase of the cell cycle. Mutations of the p53 gene are common in a wide variety of human cancers, including lung cancer. In lung cancers, point mutations of the p53 gene have been found in all histological types including approximately 45% of resected NSCLC and even more frequently in SCLC specimens. Mutant forms of the p53 protein have transforming activity and interfere with the cell-cycle regulatory function of the wild-type protein. The majority of p53 gene mutations produce proteins with altered conformation and prolonged half life; these mutant proteins accumulate in the cell nucleus and can be detected by immunohistochemical staining. But protein overexpression has been reported in the absence of mutation. p53 protein overexpression or gene mutation is reported poor prognostic factor in breast cancer, but in lung cancer, its prognostic significance is controversial. Method : We investigated the p53 abnormalities by nucleotide sequencing, polymerase chain reaction-single strand conformation polymorphism(PCR-SSCP), and immunohistochemical staining. We correlated these results with each other and survival in 75 patients with NSCLC resected with curative intent. Overexpression of the p53 protein was studied immunohistochemically in archival paraffin- embedded tumor samples using the D07(Novocastra, U.K.) antibody. Overexpression of p53 protein was defined by the nuclear staining of greater than 25% immunopositive cells in tumors. Detection of p53 gene mutation was done by PCR-SSCP and nucleotide sequencing from the exon 5-9 of p53 gene. Result: 1) Of the 75 patients, 36%(27/75) showed p53 overexpression by immunohistochemical stain. There was no survival difference between positive and negative p53 immunostaining(overall median survival of 26 months, disease free median survival of 13 months in both groups). 2) By PCR-SSCP, 27.6%(16/58) of the patients showed mobility shift. There was no significant difference in survival according to mobility shift(overall median survival of 27 in patients without mobility shift vs 20 months in patients with mobility shift, disease free median survival of 8 months vs 10 months respectively). 3) Nucleotide sequence was analysed from 29 patients, and 34.5%(10/29) had mutant p53 sequence. Patients with the presence of gene mutations showed tendency to shortened survival compared with the patients with no mutation(overall median survival of 22 vs 27 months, disease free median survival of 10 vs 20 months), but there was no statistical significance. 4) The sensitivity and specificity of immunostain based on PCR-SSCP was 67.0%, 74.0%, and that of the PCR-SSCP based on the nucleotide sequencing was 91.8%, 96.2% respectively. The concordance rate between the immunostain and PCR-SSCP was 62.5%, and the rate between the PCR-SSCP and nucleotide sequencing was 95.3%. Conclusion : In terms of detection of p53 gene mutation, PCR-SSCP was superior to immunostaining. p53 gene abnormalities either overexpression or mutation were not a significant prognostic factor in NSCLC patients resected with curative intent. However, patients with the mutated p53 gene showed the trends of early relapse.

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