• Title/Summary/Keyword: predictive marker

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Plant breeding in the 21st century: Molecular breeding and high throughput phenotyping

  • Sorrells, Mark E.
    • Proceedings of the Korean Society of Crop Science Conference
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    • 2017.06a
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    • pp.14-14
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    • 2017
  • The discipline of plant breeding is experiencing a renaissance impacting crop improvement as a result of new technologies, however fundamental questions remain for predicting the phenotype and how the environment and genetics shape it. Inexpensive DNA sequencing, genotyping, new statistical methods, high throughput phenotyping and gene-editing are revolutionizing breeding methods and strategies for improving both quantitative and qualitative traits. Genomic selection (GS) models use genome-wide markers to predict performance for both phenotyped and non-phenotyped individuals. Aerial and ground imaging systems generate data on correlated traits such as canopy temperature and normalized difference vegetative index that can be combined with genotypes in multivariate models to further increase prediction accuracy and reduce the cost of advanced trials with limited replication in time and space. Design of a GS training population is crucial to the accuracy of prediction models and can be affected by many factors including population structure and composition. Prediction models can incorporate performance over multiple environments and assess GxE effects to identify a highly predictive subset of environments. We have developed a methodology for analyzing unbalanced datasets using genome-wide marker effects to group environments and identify outlier environments. Environmental covariates can be identified using a crop model and used in a GS model to predict GxE in unobserved environments and to predict performance in climate change scenarios. These new tools and knowledge challenge the plant breeder to ask the right questions and choose the tools that are appropriate for their crop and target traits. Contemporary plant breeding requires teams of people with expertise in genetics, phenotyping and statistics to improve efficiency and increase prediction accuracy in terms of genotypes, experimental design and environment sampling.

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The Utility of Perturbation, Non-linear dynamic, and Cepstrum measures of dysphonia according to Signal Typing (음성 신호 분류에 따른 장애 음성의 변동률 분석, 비선형 동적 분석, 캡스트럼 분석의 유용성)

  • Choi, Seong Hee;Choi, Chul-Hee
    • Phonetics and Speech Sciences
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    • v.6 no.3
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    • pp.63-72
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    • 2014
  • The current study assessed the utility of acoustic analyses the most commonly used in routine clinical voice assessment including perturbation, nonlinear dynamic analysis, and Spectral/Cepstrum analysis based on signal typing of dysphonic voices and investigated their applicability of clinical acoustic analysis methods. A total of 70 dysphonic voice samples were classified with signal typing using narrowband spectrogram. Traditional parameters of %jitter, %shimmer, and signal-to-noise ratio were calculated for the signals using TF32 and correlation dimension(D2) of nonlinear dynamic parameter and spectral/cepstral measures including mean CPP, CPP_sd, CPPf0, CPPf0_sd, L/H ratio, and L/H ratio_sd were also calculated with ADSV(Analysis of Dysphonia in Speech and VoiceTM). Auditory perceptual analysis was performed by two blinded speech-language pathologists with GRBAS. The results showed that nearly periodic Type 1 signals were all functional dysphonia and Type 4 signals were comprised of neurogenic and organic voice disorders. Only Type 1 voice signals were reliable for perturbation analysis in this study. Significant signal typing-related differences were found in all acoustic and auditory-perceptual measures. SNR, CPP, L/H ratio values for Type 4 were significantly lower than those of other voice signals and significant higher %jitter, %shimmer were observed in Type 4 voice signals(p<.001). Additionally, with increase of signal type, D2 values significantly increased and more complex and nonlinear patterns were represented. Nevertheless, voice signals with highly noise component associated with breathiness were not able to obtain D2. In particular, CPP, was highly sensitive with voice quality 'G', 'R', 'B' than any other acoustic measures. Thus, Spectral and cepstral analyses may be applied for more severe dysphonic voices such as Type 4 signals and CPP can be more accurate and predictive acoustic marker in measuring voice quality and severity in dysphonia.

LCN2 Promoter Methylation Status as Novel Predictive Marker for Microvessel Density and Aggressive Tumor Phenotype in Breast Cancer Patients

  • Meka, Phanni bhushann;Jarjapu, Sarika;Nanchari, Santhoshi Rani;Vishwakarma, Sandeep Kumar;Edathara, Prajitha Mohandas;Gorre, Manjula;Cingeetham, Anuradha;Vuree, Sugunakar;Annamaneni, Sandhya;Dunna, Nageswara Rao;Mukta, Srinivasulu;Triveni, B;Satti, Vishnupriya
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.12
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    • pp.4965-4969
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    • 2015
  • LCN2 (Lipocalin 2) is a 25 KD secreted acute phase protein, reported to be a novel regulator of angiogenesis in breast cancer. Up regulation of LCN2 had been observed in multiple cancers including breast cancer, pancreatic cancer and ovarian cancer. However, the role of LCN2 promoter methylation in the formation of microvessels is poorly understood. The aim of this study was to analyze the association of LCN 2 promoter methylation with microvessel formation and tumor cell proliferation in breast cancer patients. The LCN2 promoter methylation status was studied in 64 breast cancer tumors by methylation specific PCR (MSP). Evaluation of microvessel density (MVD) and Ki67 cell proliferation index was achieved by immunohistochemical staining using CD34 and MIB-1 antibodies, respectively. LCN2 promoter unmethylation status was observed in 43 (67.2%) of breast cancer patients whereas LCN2 methylation status was seen in 21 (32.8%). Further, LCN2 promoter unmethylation status was associated with aggressive tumor phenotype and elevated mean MVD in breast cancer patients.

High Monocarboxylate Transporter 4 Protein Expression in Stromal Cells Predicts Adverse Survival in Gastric Cancer

  • Yan, Ping;Li, Yu-Hong;Tang, Zhi-Jiao;Shu, Xiang;Liu, Xia
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.20
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    • pp.8923-8929
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    • 2014
  • Background: Increasing evidence suggests that stromal monocarboxylate transporter 4 (MCT4) and carbonic anhydrase IX (CA IX) may play key roles in tumor development. However, their clinical value remains largely unexplored in gastric cancer (GC). The present study aimed to determine clinicopathological significance and prognostic values of stromal MCT4 and CA IX in GC. Materials and Methods: Specimens from 143 GC patients were immunohistochemically stained using polyclonal anti-MCT4 and anti-CA IX antibodies. Expression was correlated with patient clinicopathologic characteristics and survival data. Results: High stromal MCT4 expression was detected in 72 of 143 (50.3%) GCs and high CA IX in 74 (51.7%). Both high stromal MCT4 and CA IX were correlated with advanced TNM stage (p=0.000; p=0.000). High CA IX expression was positively related to depth of invasion (p=0.022) and positive lymph nodes (p=0.002) as well. Survival analysis indicated high expression of stromal MCT4 to be an independent factor in predicting poor overall survival (OS) (HR and 95%CI=1.962, 1.032-3.729, p=0.040) and disease free survival (DFS) (HR and 95%CI=2.081, 1.158-3.741, p=0.014) of GC patients. However, high CA IX expression exhibited no significant predictive value. Conclusions: These findings suggest that high expression of stromal MCT4 and CA IX proteins is significantly correlated with GC progression. High stromal MCT4 heralds worse outcome of GC patient, suggesting a novel candidate prognostic marker and therapeutic target.

An Australian Retrospective Study to Evaluate the Prognostic Role of p53 and eIF4E Cancer Markers in Patients with Head and Neck Squamous Cell Carcinoma (HNSCC): Study Protocol

  • Singh, Jagtar;Jayaraj, Rama;Baxi, Siddhartha;Mileva, Mariana;Curtin, Justin;Thomas, Mahiban
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.8
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    • pp.4717-4721
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    • 2013
  • Complete surgical resection of the primary tumour is a crucial predictive step for head and neck squamous cell carcinoma (HNSCC), because incomplete resection may lead to increase in the recurrence rate. Molecular cancer markers have been investigated as potential predictors of prognosis marker, to identify patients who are at high risk of local recurrence. This retrospective study aimed to determine the prognostic correlation between p53 and eIF4E expression and clinical characteristics, recurrence and overall survival. Forty eight HNSCC patients were selected between 2006 and 2009 diagnosed at the Royal Darwin Hospital, Darwin, Northern Territory, Australia. Out of 48, only those 24 with negative surgical margins with hematoxylin and eosin (HandE) were chosedn for further analysis. A total of 77 surgical margins were obtained and subsequently analysed by immunohistochemical (IHC) staining with monoclonal p53 and polyclonal eIF4E antibodies. Contingency table and ${\chi}^2$-test were used to investigate the correlation between p53 and eIF4E expression and clinical characteristics, recurrence and overall survival of the HNSCC patients. The follow up period was 74 months (range 1-74 months). The Kaplan-Meier method was used to generate recurrence and survival curves. This is a first retrospective study of Northern Territory patients, including Indigenous and non-Indigenous Australians. Molecular study of surgical margins could help to identify patients with and without clear margins after surgery and help in choice of the most appropriate adjuvant treatment for HNSCC patients.

Expression of Matrix Metalloproteinase-2, but not Caspase-3, Facilitates Distinction between Benign and Malignant Thyroid Follicular Neoplasms

  • Sanii, Sanaz;Saffar, Hiva;Tabriz, Hedieh M.;Qorbani, Mostafa;Haghpanah, Vahid;Tavangar, Seyed M.
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.5
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    • pp.2175-2178
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    • 2012
  • Purpose: Definite diagnosis of follicular thyroid carcinoma (FTC) is based on the presence of capsular or vascular invasion. To date, no reliable and practical method has been introduced to discriminate this malignant neoplasm from follicular thyroid adenoma (FTA) in fine needle aspiration biopsy material. Matrix metalloproteinase-2 (MMP-2), by degrading extracellular matrix, and caspase-3, by induction of apoptosis, have been shown to play important roles in carcinogenesis and aggressive behavior in many tumor types. The aim of this study was to examine expression of MMP-2 and caspase-3 in thyroid follicular neoplasms and to determine their usefulness for differential diagnosis. Method: Sixty FTAs and 41 FTCs were analysed immunohistochemically for MMP-2 and caspase-3. Result: MMP-2 was positive in 4 FTCs (9.8%), but in none of FTAs, with statistical significance (p= 0.025). Caspase-3 was positive in 30 (50%) of FTAs and in 27 (65.9%) of FTCs. Conclusion: Our results show MMP-2 expression only in FTCs and suggest that this protein may be a useful marker to confirm diagnosis of FTC versus FTA with 100% specificity and 100% predictive value of a positive test. We failed to show any differential diagnostic value for caspase-3 in thyroid follicular neoplasms.

The relationship between odd- and branched-chain fatty acids and microbial nucleic acid bases in rumen

  • Liu, Keyuan;Hao, Xiaoyan;Li, Yang;Luo, Guobin;Zhang, Yonggen;Xin, Hangshu
    • Asian-Australasian Journal of Animal Sciences
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    • v.30 no.11
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    • pp.1590-1597
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    • 2017
  • Objective: This study aims to identify the relationship between odd- and branched-chain fatty acids (OBCFAs) and microbial nucleic acid bases in the rumen, and to establish a model to accurately predict microbial protein flow by using OBCFA. Methods: To develop the regression equations, data on the rumen contents of individual cows were obtained from 2 feeding experiments. In the first experiment, 3 rumen-fistulated dry dairy cows arranged in a $3{\times}3$ Latin square were fed diets of differing forage to concentration ratios (F:C). The second experiment consisted of 9 lactating Holstein dairy cows of similar body weights at the same stage of pregnancy. For each lactation stage, 3 cows with similar milk production were selected. The rumen contents were sampled at 4 time points of every two hours after morning feeding 6 h, and then to analyse the concentrations of OBCFA and microbial nucleic acid bases in the rumen samples. Results: The ruminal bacteria nucleic acid bases were significantly influenced by feeding diets of differing forge to concentration ratios and lactation stages of dairy cows (p<0.05). The concentrations of OBCFAs, especially odd-chain fatty acids and C15:0 isomers, strongly correlated with the microbial nucleic acid bases in the rumen (p<0.05). The equations of ruminal microbial nucleic acid bases established by ruminal OBCFAs contents showed a good predictive capacity, as indicated by reasonably low standard errors and high R-squared values. Conclusion: This finding suggests that the rumen OBCFA composition could be used as an internal marker of rumen microbial matter.

Concurrent Hypermethylation of SFRP2 and DKK2 Activates the Wnt/β-Catenin Pathway and Is Associated with Poor Prognosis in Patients with Gastric Cancer

  • Wang, Hao;Duan, Xiang-Long;Qi, Xiao-Li;Meng, Lei;Xu, Yi-Song;Wu, Tong;Dai, Peng-Gao
    • Molecules and Cells
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    • v.40 no.1
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    • pp.45-53
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    • 2017
  • Aberrant hypermethylation of Wnt antagonists has been observed in gastric cancer. A number of studies have focused on the hypermethylation of a single Wnt antagonist and its role in regulating the activation of signaling. However, how the Wnt antagonists interacted to regulate the signaling pathway has not been reported. In the present study, we systematically investigated the methylation of some Wnt antagonist genes (SFRP2, SFRP4, SFRP5, DKK1, DKK2, and APC) and their regulatory role in carcinogenesis. We found that aberrant promoter methylation of SFRP2, SFRP4, DKK1, and DKK2 was significantly increased in gastric cancer. Moreover, concurrent hypermethylation of SFRP2 and DKK2 was observed in gastric cancer and this was significantly associated with increased expression of ${\beta}-catenin$, indicating that the joint inactivation of these two genes promoted the activation of the Wnt signaling pathway. Further analysis using a multivariate Cox proportional hazards model showed that DKK2 methylation was an independent prognostic factor for poor overall survival, and the predictive value was markedly enhanced when the combined methylation status of SFRP2 and DKK2 was considered. In addition, the methylation level of SFRP4 and DKK2 was correlated with the patient's age and tumor differentiation, respectively. In conclusion, epigenetic silencing of Wnt antagonists was associated with gastric carcinogenesis, and concurrent hypermethylation of SFRP2 and DKK2 could be a potential marker for a prognosis of poor overall survival.

The Histopathological Examination for Diagnosis of MALT Lymphoma in the Stomach

  • Lee, Tae Hee;Hyun, Sung Hee;Kim, In Sik
    • Korean Journal of Clinical Laboratory Science
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    • v.46 no.3
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    • pp.91-98
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    • 2014
  • Primary gastric lymphoma (PGL) is derived from mucosa-associated lymphoid tissue (MALT) and it differs from nodal lymphoma in histologic features and biologic behavior. Recent studies have showed that Helicobacter pylori (H.pylori ) infection is closely related to the development of low grade gastric lymphoma, and eradication of the infection induces regression of the tumor. H. pylori infection is known to be important to the development of gastric MALT lymphoma. The aim of this study was to elucidate the histopathological behavior of PGL according to the concept of MALT and to compare the predictive value of tests frequently used for diagnosis of H. pylori. The histological features of gastric lymphoma arising from MALT are the replacement of glands by uniform dense infiltration of centrocyte-like cells in the lamina propria and lymphoidepithelial lesion. H. pylori-associated histologic changes of neutrophilic infiltration, lymphoid follicle or aggregates formation and intestinal metaplasia, and H. pylori immunoreactivity were analyzed. Detection of H. pylori in chronic active gastritis and peptic ulcer suggests a possible role of H. pylori in the pathogenesis. Giemsa, Toluidine blue and Long H&E stains were used in H. pylori detection. Histopathological examination of gastric biopsy specimens revealed lymphoepithelial lesions pathognomonic of MALT lymphoma, and immunohistochemical staining for CD20 was diffusely positive. CD3 was positive in reactive T cells. PAX-5 was negative except the follicle. Bcl-2, cytokeratin, Ki-67, and c-myc were positive. The findings may indicate a predictable transition of low grade to high grade, and c-myc may be used as a valuable marker before molecular pathology diagnosis.

Outcomes of 1st Remission Induction Chemotherapy in Acute Myeloid Leukemia Cytogenetic Risk Groups

  • Zehra, Samreen;Najam, Rahela;Farzana, Tasneem;Shamsi, Tahir Sultan
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.12
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    • pp.5251-5256
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    • 2016
  • Background: Diagnostic karyotyping analysis is routinely used in acute myeloid leukemia (AML) clinics. Categorization of patients into risk stratified groups (favorable, intermediate and adverse) according to cytogenetic findings can serve as a valuable independent prognostic factor. Method and Material: A retrospective descriptive study was conducted based on the patient records of newly diagnosed non-M3 AML young adult cases undergoing standard 3+7 i.e, Daunorubicin and Ara-C (DA) as remission induction chemotherapy. Diagnostic cytogenetic analysis reports were analyzed to classify the patients into risk stratified groups according to South West Oncology Group criteria and prognostic significance was measured with reference to achievement of haematological remission after 1st induction chemotherapy. Results:A normal karyotype was commonly expressed, found in 47.2% of patients, while 65% (n=39) appeared to have intermediate risk cytogenetics, and 13.3% (n=8) adverse or unclassified findings. Favourable cytogenetics was least frequent in the patient cohort, accounting for only 8.3 % (n=5).The impact of cytogenetic risk groups on achievement of haematological remission was evaluated by applying Pearson Chi-square, and was found to be non-significant (df=12, p=0.256) but when the outcomes of favourable risk groups with intermediate, adverse and unclassified findings compared, results were highly significant (df=6, p=0.000) for each comparison. In patients of the favourable cytogenetic risk group, HR?? was reported in 40% (n=2/5), as compared to 62.2% (n=23/37) in the intermediate cytogenetic risk group, 57.1% (n=4/7) in the adverse cytogenetic risk group and 28.6% (n=2/7) in hte unclassified cytogenetic risk group. Conclusion: Cytogenetic risk stratification for AML cases following criteria provided by international guidelines did not produce conclusive results in our Pakistani patients. However, we cannot preclude an importance as the literature clearly supports the use of pretreatment karyotyping analysis as a significant predictive marker for clinical outcomes. The apparent differences between Pakistani and Western studies indicate an urgent need to develop risk stratification guidelines according to the specific cytogenetic makeup of South Asian populations.