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03 11, 2020;10 (1): 4526.

Comprehensive transcriptome profiling of Taiwanese colorectal cancer implicates an ethnic basis for pathogenesis.

Shao-Min Wu, Wen-Sy Tsai, Sum-Fu Chiang, Yi-Hsuan Lai, Chung-Pei Ma, Jian-Hua Wang, Jiarong Lin, Pei-Shan Lu, Chia-Yu Yang, Bertrand Chin-Ming Tan, Hsuan Liu
Author Information
  1. Shao-Min Wu: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan. ORCID
  2. Wen-Sy Tsai: Division of Colon and Rectal Surgery, Lin-Kou Medical Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
  3. Sum-Fu Chiang: Division of Colon and Rectal Surgery, Lin-Kou Medical Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
  4. Yi-Hsuan Lai: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
  5. Chung-Pei Ma: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
  6. Jian-Hua Wang: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
  7. Jiarong Lin: Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan.
  8. Pei-Shan Lu: Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan.
  9. Chia-Yu Yang: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
  10. Bertrand Chin-Ming Tan: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan. btan@mail.cgu.edu.tw.
  11. Hsuan Liu: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan. liu-hsuan@mail.cgu.edu.tw.
PMID: 32161294 DOI: 10.1038/s41598-020-61273-y

Abstract

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers worldwide. While both genetic and environmental factors have been linked to the incidence and mortality associated with CRC, an ethnic aspect of its etiology has also emerged. Since previous large-scale cancer genomics studies are mostly based on samples of European ancestry, the patterns of clinical events and associated mechanisms in other minority ethnic patients suffering from CRC are largely unexplored. We collected 104 paired and adjacent normal tissue and CRC tumor samples from Taiwanese patients and employed an integrated approach - paired expression profiles of mRNAs and microRNAs (miRNAs) combined with transcriptome-wide network analyses - to catalog the molecular signatures of this regional cohort. On the basis of this dataset, which is the largest ever reported for this type of systems analysis, we made the following key discoveries: (1) In comparison to the The Cancer Genome Atlas (TCGA) data, the Taiwanese CRC tumors show similar perturbations in expressed genes but a distinct enrichment in metastasis-associated pathways. (2) Recurrent as well as novel CRC-associated gene fusions were identified based on the sequencing data. (3) Cancer subtype classification using existing tools reveals a comparable distribution of tumor subtypes between Taiwanese cohort and TCGA datasets; however, this similarity in molecular attributes did not translate into the predicted subtype-related clinical outcomes (i.e., death event). (4) To further elucidate the molecular basis of CRC prognosis, we developed a new stratification strategy based on miRNA-mRNA-associated subtyping (MMAS) and consequently showed that repressed WNT signaling activity is associated with poor prognosis in Taiwanese CRC. In summary, our findings of distinct, hitherto unreported biosignatures underscore the heterogeneity of CRC tumorigenesis, support our hypothesis of an ethnic basis of disease, and provide prospects for translational medicine.

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MeSH Term

Biomarkers, Tumor
Cell Transformation, Neoplastic
Colorectal Neoplasms
Computational Biology
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Male
MicroRNAs
Neoplasm Grading
Neoplasm Metastasis
Neoplasm Staging
Prognosis
RNA Interference
RNA, Messenger
Taiwan
Transcriptome

Chemicals

Biomarkers, Tumor
MicroRNAs
RNA, Messenger
Journal Article Research Support, Non-U.S. Gov't

Links to CNCB-NGDC Resources

GEN: GEND000553 (Comprehensively identification of miRNA-mRNA regulation network in Taiwanese colorectal cancer by using next-generation sequencing)

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