Dataset Information

Multi-omics landscapes of colorectal cancer subtypes discriminated by an individualized prognostic signature for 5-fluorouracil-based chemotherapy.

ABSTRACT: Until recently, few prognostic signatures for colorectal cancer (CRC) patients receiving 5-fluorouracil (5-FU)-based chemotherapy could be used in clinical practice. Here, using transcriptional profiles for a panel of cancer cell lines and three cohorts of CRC patients, we developed a prognostic signature based on within-sample relative expression orderings (REOs) of six gene pairs for stage II-III CRC patients receiving 5-FU-based chemotherapy. This REO-based signature had the unique advantage of being insensitive to experimental batch effects and free of the impractical data normalization requirement. After stratifying 184 CRC samples with multi-omics data from The Cancer Genome Atlas into two prognostic groups using the REO-based signature, we further revealed that patients with high recurrence risk were characterized by frequent gene copy number aberrations reducing 5-FU efficacy and DNA methylation aberrations inducing distinct transcriptional alternations to confer 5-FU resistance. In contrast, patients with low recurrence risk exhibited deficient mismatch repair and carried frequent gene mutations suppressing cell adhesion. These results reveal the multi-omics landscapes determining prognoses of stage II-III CRC patients receiving 5-FU-based chemotherapy.

SUBMITTER: Tong M

PROVIDER: S-EPMC5399173 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Multi-omics landscapes of colorectal cancer subtypes discriminated by an individualized prognostic signature for 5-fluorouracil-based chemotherapy.

Tong M M Zheng W W Li H H Li X X Ao L L Shen Y Y Liang Q Q Li J J Hong G G Yan H H Cai H H Li M M Guan Q Q Guo Z Z

Oncogenesis 20160718 7

Until recently, few prognostic signatures for colorectal cancer (CRC) patients receiving 5-fluorouracil (5-FU)-based chemotherapy could be used in clinical practice. Here, using transcriptional profiles for a panel of cancer cell lines and three cohorts of CRC patients, we developed a prognostic signature based on within-sample relative expression orderings (REOs) of six gene pairs for stage II-III CRC patients receiving 5-FU-based chemotherapy. This REO-based signature had the unique advantage ...[more]

PMID: 27429074

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Project description:BackgroundColorectal adenocarcinoma (COAD) is one of the most common malignancies and angiogenesis is vital to the development of cancer. Here, we explored the roles of angiogenesis-related genes (ARGs) that affect the prognosis of COAD and constructed risk models to assess patient prognosis, immune characteristics, and treatment outcomes.MethodsWe comprehensively characterized the transcriptional and genetic modifications of 48 ARGs in COAD and evaluated the expression patterns. We identified two ARG subgroups using the consensus clustering algorithm. Based on the differentially expressed genes (DEGs) of two ARG subtypes, we calculated risk score, namely ARG_scores, and calssified COAD patients into different risk groups. To investigate the expression of ARG_score-related genes, qRT-PCR was performed. Subsequently, we mapped the nomogram to visually and accurately describe the value of the application of ARG_score. Finally, the correlation between ARG_score and clinical features, immune infiltration along with drug sensitivity were explored.ResultsWe identified two ARG related subgroups and there were great differences in overall survival (OS) and tumor microenvironment. Then, we created an ARG_score for predicting overall survival based on eight DEGs and confirmed its reliable predictive power in COAD patients, with higher ARG_score associated with worse prognosis. Furthermore, eight ARG_score-related genes expression was investigated by qRT-PCR. To make the ARG_score clinically feasible, we created a highly reliable nomogram. We also found a higher proportion of microsatellite instability-high (MSI-H) and higher tumor mutational burden (TMB) in the high-risk group. In addition, ARG_score was notably correlated with cancer stem cell indices and drug sensitivity.ConclusionThis scoring model has potential clinical application value in the prognosis, immune microenvironment and therapeutic drug sensitivity of COAD, which provides new insights for personalized treatment.

Dataset Information

Multi-omics landscapes of colorectal cancer subtypes discriminated by an individualized prognostic signature for 5-fluorouracil-based chemotherapy.

Publications

Multi-omics landscapes of colorectal cancer subtypes discriminated by an individualized prognostic signature for 5-fluorouracil-based chemotherapy.

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