Project description:In this study, we utilized microRNA expression profiling to assess risk of HCC recurrence after liver resection. We examined microRNA expression profiling in paired tumor and non-tumor liver tissues of 73 HCC patients with mild cirrhosis (Child-Pugh A/B) who satisfy Milan Criteria. We constructed prediction models of recurrence-free survival using Cox proportional hazard model and principal component analysis.
Project description:Lung cancer remains the leading cause of cancer death worldwide. Overall 5-year survival is about 10-15% and despite curative intent surgery, treatment failure is primarily due to recurrent disease. Conventional prognostic markers are unable to determine which patients with completely resected disease within each stage group are likely to relapse. To identify a gene signature associated with recurrent squamous cell carcinoma (SCC) of lung, we analyzed primary tumour gene expression for a total of fifty-one SCCs (stage I-III) on 22,323 element microarrays, comparing expression profiles for individuals who remained disease-free for a minimum of 36 months with those from individuals whose disease recurred within 18 months of complete resection. Cox proportional hazards modeling with leave-one-out cross-validation identified a 70-gene capable of predicting the likelihood of tumor recurrence and a 79-gene signature predictive for overall survival. These two signatures were pooled to generate a 111-gene classifier which achieved an overall predictive accuracy for disease recurrence of 72% (77% sensitivity, 67% specificity) in an independent set of fifty-eight stage I-III SCCs. This classifier also predicted differences in survival (log-rank P=0.0008, hazard ratio (HR), 3.8 [95% confidence interval, 1.6-8.7]), and was superior to conventional prognostic markers such as TNM stage or N stage in predicting patient outcome. Genome-wide profiling has revealed a distinct gene expression profile for recurrent lung SCC which may be clinically useful as a prognostic tool. Expression profiling using 22K element microarrays of 51 primary lung squamous cell carcinomas.
Project description:Lung cancer remains the leading cause of cancer death worldwide. Overall 5-year survival is about 10-15% and despite curative intent surgery, treatment failure is primarily due to recurrent disease. Conventional prognostic markers are unable to determine which patients with completely resected disease within each stage group are likely to relapse. To identify a gene signature associated with recurrent adenocarcinoma (AC) of lung, we analyzed primary tumour gene expression for a total of 48 stage I ACs on 22,323 element microarrays, comparing expression profiles for individuals who remained disease-free for a minimum of 36 months with those from individuals whose disease recurred within 18 months of complete resection. Genome-wide profiling has revealed a distinct gene expression profile for recurrent lung AC which may be clinically useful as a prognostic tool. Keywords: non-small cell lung carcinoma, squamous cell, tumor recurrence, expression profiling
Project description:Lung cancer remains the leading cause of cancer death worldwide. Overall 5-year survival is about 10-15% and despite curative intent surgery, treatment failure is primarily due to recurrent disease. Conventional prognostic markers are unable to determine which patients with completely resected disease within each stage group are likely to relapse. To identify a gene signature associated with recurrent squamous cell carcinoma (SCC) of lung, we analyzed primary tumour gene expression for a total of fifty-one SCCs (stage I-III) on 22,323 element microarrays, comparing expression profiles for individuals who remained disease-free for a minimum of 36 months with those from individuals whose disease recurred within 18 months of complete resection. Cox proportional hazards modeling with leave-one-out cross-validation identified a 70-gene capable of predicting the likelihood of tumor recurrence and a 79-gene signature predictive for overall survival. These two signatures were pooled to generate a 111-gene classifier which achieved an overall predictive accuracy for disease recurrence of 72% (77% sensitivity, 67% specificity) in an independent set of fifty-eight stage I-III SCCs. This classifier also predicted differences in survival (log-rank P=0.0008, hazard ratio (HR), 3.8 [95% confidence interval, 1.6-8.7]), and was superior to conventional prognostic markers such as TNM stage or N stage in predicting patient outcome. Genome-wide profiling has revealed a distinct gene expression profile for recurrent lung SCC which may be clinically useful as a prognostic tool. Keywords: non-small cell lung carcinoma, squamous cell, tumor recurrence, expression profiling
Project description:Background: One of the main fields of lung cancer research is identifying patients who are at high risk of post-resection recurrence. Individual recurrence risk evaluation by accurate but simple and reproducible method is needed for the clinical practice. Results: The log-rank test and further selection by our criteria of assayability generated 87 genes from microarray data with significant level 5%. Of these, by PTQ-PCR, the expression of most significant 18 genes was obtained. Using these gene expression information and clinical parameters, by stepwise variable selection method, the recurrence prediction model, which composed of 6 genes (CALB1, MMP7, SLC1A7, GSTA1, CCL19, IFI44) and pStage and cell differentiation, were developed. Validation into the two independent cohorts showed good results of the proposed model (p=0.0314, 0.0305, respectively). The predicted median recurrence-free survival times for each patient were reflected real ones well. Conclusions: Our method of individualized recurrence risk prediction is accurate, technically simple and reproducible to be used in clinical practice. Therefore, it would be useful in customizing the lung cancer management strategies. Keywords: Recurrence Free Survival Analysis
Project description:Despite surgical treatment of stage I non-small cell lung cancer (NSCLC), one third of patients will eventually have a recurrence. Robust prognostic markers are required to better manage therapy options. MicroRNAs play important roles in human cancers. The purpose of this study is to identify miRNA expression profiles that would better predict prognosis. Small RNAs extracted from formalin-fixed and paraffin-embedded (FFPE) tumor tissues of 357 stage I NSCLC patients were profiled on the human MicroRNA expression profiling V2 panel (Illumina). The expression differences between cancer subtypes were compared by t tests. The association of miRNA expression profile with recurrence free survival (RFS) was assessed using partial Cox regression models. Two miRNA signatures that are highly predictive of RFS were identified. The first contained 32 miRNAs derived from 357 stage I NSCLC patients independent of cancer subtype; while the second containing 27 miRNAs was adenocarcinoma specific. Both of them were validated using FFPE and/or fresh frozen tissues in independent data set with 170 stage I patients. This has important prognostic or therapeutic implications for the management of patients. The identified miRNAs hold great potential as targets for histology-specific treatment or prevention and treatment of recurrent disease. Small RNAs extracted from formalin-fixed and paraffin-embedded (FFPE) tumor tissues of 357 stage I NSCLC patients were profiled on the human MicroRNA expression profiling V2 panel (Illumina).
Project description:Early-stage epithelial ovarian cancer (eEOC) patients have a generally favorable prognosis but heterogeneous behavior at recurrence. Accurate prediction of the risk of relapse is still a major concern, essentially to avoid overtreatment. We have identified a robust miRNA-based signature named MiROvaR able to predict early disease recurrence in case materials of mostly advanced-stage EOC patients. We challenged MiROvaR in the eEOC sub-setting (stage IA-IIB) and it proved to accurately classify eEOC patients according to their risk of relapse.
Project description:Background:; One of the main fields of lung cancer research is identifying patients who are at high risk of post-resection recurrence. Individual recurrence risk evaluation by accurate but simple and reproducible method is needed for the clinical practice. Results:; The log-rank test and further selection by our criteria of assayability generated 87 genes from microarray data with significant level 5%. Of these, by PTQ-PCR, the expression of most significant 18 genes was obtained. Using these gene expression information and clinical parameters, by stepwise variable selection method, the recurrence prediction model, which composed of 6 genes (CALB1, MMP7, SLC1A7, GSTA1, CCL19, IFI44) and pStage and cell differentiation, were developed. Validation into the two independent cohorts showed good results of the proposed model (p=0.0314, 0.0305, respectively). The predicted median recurrence-free survival times for each patient were reflected real ones well. Conclusions:; Our method of individualized recurrence risk prediction is accurate, technically simple and reproducible to be used in clinical practice. Therefore, it would be useful in customizing the lung cancer management strategies. Experiment Overall Design: Methods: Experiment Overall Design: At first, we selected the statistically significant genes from the analysis of time-to-recurrence and censoring information from 138 whole-genome wide microarray data. Then, we further reduced the number of genes which could be reliably reproducible by RTQ-PCR. With these assayable genes and clinical parameters, construction of recurrence prediction model by Cox proportional hazard regression was done. After validation into two independent cohorts (n=59 and n=56), the model was transformed into recurrence prediction for the each patient.