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

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...

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Bibliographic Details
Published in:Scientific reports 2020-03, Vol.10 (1), p.4526, Article 4526
Main Authors: Wu, Shao-Min, Tsai, Wen-Sy, Chiang, Sum-Fu, Lai, Yi-Hsuan, Ma, Chung-Pei, Wang, Jian-Hua, Lin, Jiarong, Lu, Pei-Shan, Yang, Chia-Yu, Tan, Bertrand Chin-Ming, Liu, Hsuan
Format: Article
Language:English
Subjects:
Biomarkers, Tumor
Cancer
Cell Transformation, Neoplastic - genetics
Colorectal cancer
Colorectal carcinoma
Colorectal Neoplasms - epidemiology
Colorectal Neoplasms - etiology
Computational Biology - methods
Environmental factors
Etiology
Female
Gene expression
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Genomics
Humans
Male
Metastases
MicroRNAs
MicroRNAs - genetics
miRNA
Neoplasm Grading
Neoplasm Metastasis
Neoplasm Staging
Prognosis
RNA Interference
RNA, Messenger - genetics
Taiwan - epidemiology
Transcriptome
Tumorigenesis
Wnt protein
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-020-61273-y