• Asian Pacific Journal of Cancer Prevention
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• 제13권7호
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• pp.3265-3270
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• 2012

Clinically, elevated cancer antigen 125 (CA-125) in blood predicts tumor burden in a woman's body, especially in the ovary, but cannot differentiate between malignant or benign. We here used intensive modern proteomic approaches to identify predictive proteins in the serum of women with elevated CA-125 to differentiate malignant from benign ovarian tumors. We identified differentially expressed proteins in serum samples of ovarian cancer (OC) patients, benign ovarian tumor (BT) patients, and healthy control women using mass spectrometry-based quantitative proteomics. Both the OC and BT patients had elevated CA-125. Quantitation was achieved using isobaric tags for relative and absolute quantitation. We obtained 124 quantified differential serum proteins in OC compared with BT. Two proteins, apolipoprotein A-4 (APOA4) and natural resistance-associated macrophage 1, were verified using Western blotting. Proteome profiling applied to OC cases identified several differential serum proteins in the serum of women with elevated CA-125. A novel protein, APOA4, has the potential to be a marker for malignant tumor differentiation in the serum of women with elevated CA-125.

• Asian Pacific Journal of Cancer Prevention
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• 제13권7호
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• pp.3489-3493
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• 2012

Hepatocellular carcinoma (HCC), the most common primary hepatic tumor, is highly prevalent in the Asia-Pacific region, including Thailand. Many genetic and epigenetic alterations in HCC have been elucidated. The aim of this study was to determine whether aberrant methylation of the suppressor of cytokine signaling 1 gene (SOCS1) occurs in HCCs. Methylation specific-PCR assays were performed to identify the methylation status of SOCS1 in 29 tumors and their corresponding normal liver tissues. An abnormal methylation status was detected in 17 (59%), with a higher prevalence of aberrant SOCS1 methylation significantly correlating with HCC treated without chemotherapy (OR=0.04, 95%CI=0.01-0.31; P=0.001). This study suggests that epigenetic aberrant SOCS1 methylation may be a predictive marker for HCC patients.

• Asian Pacific Journal of Cancer Prevention
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• 제13권3호
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• pp.1049-1052
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• 2012

The purpose of this study was to evaluate expression and prognostic value of matrix metalloproteinase-7 (MMP-7) in colorectal cancer (CRC) patients. CRC tissues and corresponding distal normal mucosa tissues of 118 CRC patients were assessed by immunohistochemistry. Correlations between MMP-7 expression, patients' clinic pathological features, and overall survival rate were analyzed. We found that positive expression of MMP-7 in CRC tissues was significantly higher than that in distal normal mucosa (61.0% vs. 39.8%, p =0.001). Poor histological differentiation, advanced clinical stage and lymph node metastasis were significantly correlated with MMP-7 expression in CRC. The overall survival rate was significantly higher in the MMP-7 negative group than the positive group (Log-rank test= 9.957, p= 0.002). MMP-7 appeared as a significant independent prognostic factor through multivariate survival analysis. Collectively, we found MMP-7 expression to be correlated with progression and metastasis of CRC and thus could be used as a predictive marker of prognosis in CRC patients.

• Asian Pacific Journal of Cancer Prevention
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• 제14권2호
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• pp.695-700
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• 2013

Background: Mutations affecting the epidermal growth factor receptor (EGFR) are good predictors of clinical efficacy of EGFR tyrosine kinase inhibitors (TKI) in patients with non-small cell lung cancer. Serum carcinoembryonic antigen (CEA) levels are also regarded as predictive for the efficacy of EGFR-TKI and EGFR gene mutations. This study analyzed the association between EGFR gene mutations and clinical features, including serum tumor marker levels in lung adenocarcinomas patients. Patients and Methods: A total of 70 lung adenocarcinoma patients with complete clinical data and pathological specimens were investigated. EGFR gene mutations at exons 19 and 21 were assessed. Serum tumor markers were detected by protein chip-chemiluminescence at the corresponding time, and correlations were analyzed. Results: Mutations of the EGFR gene were detected in 27 of the 70 patients and the serum CEA and CA242 concentrations were found to be significantly associated with the incidence of EGFR gene mutations (P<0.05). The AUCs for CEA and CA242 were 0.724 (95% CI: 0.598~0.850, P<0.05) and 0.769 (95% CI: 0.523~0.800, P<0.05) respectively. Conclusions: Serum CEA and CA242 levels are associated with mutations of the EGFR gene in patients with lung adenocarcinomas.

• Molecules and Cells
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• 제42권2호
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• pp.161-165
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• 2019

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide and has high rates of metastasis. Transforming growth factor beta-inducible protein (TGFBI) is an extracellular matrix component involved in tumour growth and metastasis. However, the exact role of TGFBI in NSCLC remains controversial. Gene silencing via DNA methylation of the promoter region is common in lung tumorigenesis and could thus be used for the development of molecular biomarkers. We analysed the methylation status of the TGFBI promoter in 138 NSCLC specimens via methylation-specific PCR and evaluated the correlation between TGFBI methylation and patient survival. TGFBI promoter methylation was detected in 25 (18.1%) of the tumours and was demonstrated to be associated with gene silencing. We observed no statistical correlation between TGFBI methylation and clinicopathological characteristics. Univariate and multivariate analyses showed that TGFBI methylation is significantly associated with poor survival outcomes in adenocarcinoma cases (adjusted hazard ratio = 2.88, 95% confidence interval = 1.19-6.99, P = 0.019), but not in squamous cell cases. Our findings suggest that methylation in the TGFBI promoter may be associated with pathogenesis of NSCLC and can be used as a predictive marker for lung adenocarcinoma prognosis. Further large-scale studies are needed to confirm these findings.

• Communications for Statistical Applications and Methods
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• 제29권1호
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• pp.65-83
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• 2022

Although various statistical methods have been developed to map time-dependent genetic factors, most identified genetic variants can explain only a small portion of the estimated genetic variation in longitudinal traits. Gene-gene and gene-time/environment interactions are known to be important putative sources of the missing heritability. However, mapping epistatic gene-gene interactions is extremely difficult due to the very large parameter spaces for models containing such interactions. In this paper, we develop a Gaussian process (GP) based nonparametric Bayesian variable selection method for longitudinal data. It maps multiple genetic markers without restricting to pairwise interactions. Rather than modeling each main and interaction term explicitly, the GP model measures the importance of each marker, regardless of whether it is mostly due to a main effect or some interaction effect(s), via an unspecified function. To improve the flexibility of the GP model, we propose a novel grid-based method for the within-subject dependence structure. The proposed method can accurately approximate complex covariance structures. The dimension of the covariance matrix depends only on the number of fixed grid points although each subject may have different numbers of measurements at different time points. The deviance information criterion (DIC) and the Bayesian predictive information criterion (BPIC) are proposed for selecting an optimal number of grid points. To efficiently draw posterior samples, we combine a hybrid Monte Carlo method with a partially collapsed Gibbs (PCG) sampler. We apply the proposed GP model to a mouse dataset on age-related body weight.

• 한국작물학회:학술대회논문집
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• 한국작물학회 2022년도 추계학술대회
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• pp.233-233
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• 2022

As the world's population grows and food needs diversify, the demand for horticultural crops for beneficial traits is increasing. In order to meet this demand, it is necessary to develop suitable cultivars and breeding methods accordingly. Breeding methods have changed over time. With the recent development of sequencing technology, the concept of genomic selection (GS) has emerged as large-scale genome information can be used. GS shows good predictive ability even for quantitative traits by using various markers, breaking away from the limitations of Marker Assisted Selection (MAS). Moreover, GS using machine learning (ML) and deep learning (DL) has been studied recently. In this study, we aim to build a system that selects phenotype-related markers using the genomic information of the pepper population and trains a genomic selection model to select individuals from the validation population. We plan to establish an optimal genome wide association analysis model by comparing and analyzing five models. Validation of molecular markers by applying linkage markers discovered through genome wide association analysis to breeding populations. Finally, we plan to establish an optimal genome selection model by comparing and analyzing 12 genome selection models. Then We will use the genome selection model of the learning group in the breeding group to verify the prediction accuracy and discover a prediction model.

• Journal of Gastric Cancer
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• 제9권3호
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• pp.136-142
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• 2009

목적: 위암으로 진단받고 근치적 절제술을 시행받은 환자를 대상으로 수술 전 및 수술 후에 정기적으로 시행한 종양표지자(AFP, CEA, CA19-9, CA125)의 추적검사 결과를 분석하고 위암 재발의 조기진단과 관련한 임상적 의미를 판정하였다. 또한 종양 표지자의 위양성률과 비종양성 만성질환과의 연관성을 알아보았다. 대상 및 방법: 2003년 11월부터 2006년 11월까지 한양대학교병원에 위암으로 입원하여 근치적 절제술을 시행받은 환자 290명을 대상으로 후향적 연구를 시행하였다. CEA (정상 참고치: 5 ng/ml), CA19-9 (39 U/ml), AFP (7.0 ng/ml), CA125 (35 U/ml) 네 가지 종양표지자값을 측정하였다. 종양표지자값의 변화와 내시경적 검사를 통한 조직 검사나 방사선학적 검사를 통한 재발 여부와의 연관성을 분석하였다. 수술 후 종양의 재발은 없으나 종양표지자값이 정상 이상으로 상승한 위양성 환자에서 비종양성 만성 질환과의 연관성을 분석하였다. 결과: 재발과 관련하여 종양표지자 검사의 민감도, 특이도, 양성예측도, 음성예측도는 각각 75.0%, 64.6%, 23.1%, 94.8%였다. 재발이 발생한 36예 중 10예(27.8%)의 경우에서는 영상의학검사에서 재발이 발견되기 전 종양표지자의 상승이 먼저 나타났으며, 13예(36.1%)의 경우에서는 영상의학검사와 동시에 종양표지자의 상승이 나타났다 추적 기간 동안 재발이 발생하지 않은 254명 중 90명의 환자에서 적어도 한 가지 이상의 종양표지자가 상승하여 35.4%의 위양성를을 나타내었다. 재발의 증거가 없으나 종양표지자가 상승했던 90명의 환자 중에 70명의 환자는 추적 검사 상 수치가 정상화 되었으나(기간: $9.08\pm7.2$개월), 20명의 환자는 지속적으로 정상 수치 이상 유지되었다. 두 군 간의 성별, 나이, 성별, 림프절 전이 여부, 조직형, 병기 등의 차이는 없었으나 비종양성 만성 질환(폐질환, 간담도계 질환, 고혈압 당뇨, 흡연, 민간요법) 유무의 차이가 있었다. 만성 질환이 있는 군이 없는 군에 비해 종양표지자가 지속적으로 상승되어 있는 양상을 나타내었다(P=0.007). 결론: 위암 근치적 절제술 후 재발 진단의 목적으로 종양 표지자는 영상의학검사 등의 다른 검사와 병합하여 활용할 수 있을 것이다. 또한 비종양성 만성 질환이 있는 경우 종양표지자가 상승하는 경우도 있으므로 이에 대한 고려가 필요할 것이다.

• Nuclear Medicine and Molecular Imaging
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• 제43권4호
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• pp.301-308
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• 2009

목적: 자궁내막암의 치료 후 루틴 추적관찰로써의 FDG-PET/ET의 유용성에 대해 알아보고자 하였다. 대상 및 방법: 자궁내막암으로 치료 받은 환자 중 2004년 1월 1일부터 2008년 1월 31일 사이에 FDG-PET/CT를 시행한 101명의 환자(25-79세, 평균 50.6세)를 대상으로 하였다. 모든 환자에서 종양표지 자와 다른 영상의학적 검사(CT, MR)에 대해서도 함께 검토하였다. FDG-PET/CT상 국소 FDG 섭취를 보인 병변을 benign, equivocal, malignant로 분류하였고, equivocal과 maliganat 병변에 대하여 조직학적 혹은 임상적으로 재발유무를 판정하였다. 결과: FDG-PET/CT상 강한 섭취를 보인 경우는 19명의 30개의 병변이었다. Malignant 섭취를 보인 환자는 14명이었고, 이중 11예가 재발로 확인되었다. Equivocal 병변을 보인 환자는 5명 이었고, 이중 1예가 재발로 확인되었다. 위음성을 보인 경우는 2예가 있었고, 모두 복강내 암종증 환자로 진단되었다. 이상의 결과를 종합하였을 때, 자궁내막암의 치료 후 재발의 평가에 대한 전반적인 결과는 예민도 86 %,특이도 92 %, 양성 예측도 63 %, 음성예측도 98 %, 그리고 정확도는 91 %였다. 결론: 자궁내막암의 치료 후 루틴 추적관찰로써 FDG-PET/ET를 시행할 경우 높은 예민도, 특이도로 재발의 진단에 도움이 될 뿐만 아니라 높은 음성 예측도로 인하여 FDG-PET/CT상 음성인 경우 불필요한 추가 검사를 피할 수 있을 것으로 기대된다.

• Journal of Chest Surgery
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• 제44권1호
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• pp.44-50
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• 2011

Background: Cardiovascular complications are major causes of morbidity and mortality following non-cardiac thoracic operations. Recent studies have demonstrated that elevation of N-Terminal Pro-B-type natriuretic peptide (NT-proBNP) levels can predict cardiac complications following non-cardiac major surgery as well as cardiac surgery. However, there is little information on the correlation between lung resection surgery and NT-proBNP levels. We evaluated the role of NT-proBNP as a potential marker for the risk stratification of cardiac complications following lung resection surgery. Material and Methods: Prospectively collected data of 98 patients, who underwent elective lung resection from August 2007 to February 2008, were analyzed. Postoperative adverse cardiac events were categorized as myocardial injury, ECG evidence of ischemia or arrhythmia, heart failure, or cardiac death. Results: Postoperative cardiac complications were documented in 9 patients (9/98, 9.2%): Atrial fibrillation in 3, ECG-evidenced ischemia in 2 and heart failure in 4. Preoperative median NT-proBNP levels was significantly higher in patients who developed postoperative cardiac complications than in the rest (200.2 ng/L versus 45.0 ng/L, p=0.009). NT-proBNP levels predicted adverse cardiac events with an area under the receiver operating characteristic curve of 0.76 [95% confidence interval (CI) 0.545~0.988, p=0.01]. A preoperative NT-proBNP value of 160 ng/L was found to be the best cut-off value for detecting postoperative cardiac complication with a positive predictive value of 0.857 and a negative predictive value of 0.978. Other factors related to cardiac complications by univariate analysis were a higher American Society of Anesthesiologists grade, a higher NYHA functional class and a history of hypertension. In multivariate analysis, however, high preoperative NT-proBNP level (>160 ng/L) only remained significant. Conclusion: An elevated preoperative NT-proBNP level is identified as an independent predictor of cardiac complications following lung resection surgery.