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Published on: March 14, 2019
Stratification of Digestive Cancers with Different Pathological Features and Survival Outcomes by MicroRNA Expression
Senwei Tang1, William K K Wu1,2, Xiangchun Li1
1Institute of Digestive Disease and Department of Medicine &Therapeutics, State Key Laboratory of Digestive Disease, LKS Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong.
Abstract:
MicroRNAs (miRNAs) are aberrantly expressed in virtually all cancer types, including digestive cancers. Herein, we aggregated and systematically analyzed miRNA expression profiles of 1765 tumor samples, including esophageal, gastric, liver, pancreatic, colon and rectal cancers, obtained through small RNA sequencing by The Cancer Genome Atlas. We found that digestive cancers of different tissue origins could be differentiated according to their miRNA expression profiles. In particular, esophageal squamous cell carcinoma and esophageal adenocarcinoma exhibited distinct miRNA expression patterns. Thirteen (e.g. miR-135b, miR-182) and sixteen (e.g. miR-139, miR-133a-1, miR-490) miRNAs were commonly upregulated and downregulated in more than four cancer types, respectively. Pertinent to pathological features, low miR-181d expression was associated with microsatellite instability in colon and gastric cancers whereas low miR-106a expression was associated with hepatitis B virus infection in hepatocellular carcinoma. Progression in colon cancer could also be predicted by low let-7f-2 and high miR-106a expression. Molecular subtypes with distinct prognostic outcomes independent of tumor-node-metastasis staging were identified in hepatocellular carcinoma and colon cancer. In total, 4 novel and 6 reported associations between specific miRNAs and patients' survival were identified. Collectively, novel miRNA markers were identified to stratify digestive cancers with different pathological features and survival outcomes.
Insights
MicroRNAs (miRNAs) can distinguish between different digestive cancers. Specific miRNA patterns identify pathological features and predict patient survival, offering new markers for cancer stratification.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- MicroRNAs (miRNAs) show aberrant expression in various cancers, including digestive system malignancies.
- Understanding miRNA expression is crucial for diagnosing and treating digestive cancers.
Purpose of the Study:
- To analyze miRNA expression profiles across diverse digestive cancers.
- To identify novel miRNA biomarkers for cancer stratification and prognosis.
Main Methods:
- Systematic analysis of miRNA expression profiles from 1765 digestive tumor samples using The Cancer Genome Atlas (TCGA) small RNA sequencing data.
- Correlation analysis between miRNA expression and clinicopathological features (e.g., microsatellite instability, hepatitis B virus infection, tumor progression).
- Identification of molecular subtypes with distinct prognostic outcomes.
Main Results:
- Digestive cancers exhibit distinct miRNA expression profiles, allowing differentiation by tissue origin.
- Thirteen miRNAs were commonly upregulated and sixteen were downregulated across multiple digestive cancer types.
- Specific miRNAs (e.g., miR-181d, miR-106a, let-7f-2) correlated with pathological features and colon cancer progression.
- Novel molecular subtypes with prognostic significance were identified in hepatocellular carcinoma and colon cancer.
- Four new and six known miRNA-survival associations were discovered.
Conclusions:
- miRNA expression profiling can effectively differentiate digestive cancers.
- Novel miRNA markers were identified for stratifying digestive cancers based on pathological features and survival outcomes.
- These findings provide a foundation for developing targeted miRNA-based diagnostics and therapeutics for digestive cancers.
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