Analysis of multi-omics differences in left-side and right-side colon cancer

Yanyi Huang; Jinzhong Duanmu; Yushu Liu; Mengyun Yan; Taiyuan Li; Qunguang Jiang

doi:10.7717/peerj.11433

Analysis of multi-omics differences in left-side and right-side colon cancer

PeerJ. 2021 May 12:9:e11433. doi: 10.7717/peerj.11433. eCollection 2021.

Authors

Yanyi Huang^#^{1

2}, Jinzhong Duanmu^#¹, Yushu Liu^{1

2}, Mengyun Yan^{1

3}, Taiyuan Li¹, Qunguang Jiang¹

Affiliations

¹ Department of Gastrointestinal Surgery, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
² Nanchang University, The Second Clinical Medicine College, Nanchang, Jiangxi, China.
³ Nanchang University, The First Clinical Medicine College, Nanchang, Jiangxi, China.

^# Contributed equally.

Abstract

Background: Colon cancer is one of the most common tumors in the digestive tract. Studies of left-side colon cancer (LCC) and right-side colon cancer (RCC) show that these two subtypes have different prognoses, outcomes, and clinical responses to chemotherapy. Therefore, a better understanding of the importance of the clinical classifications of the anatomic subtypes of colon cancer is needed.

Methods: We collected colon cancer patients' transcriptome data, clinical information, and somatic mutation data from the Cancer Genome Atlas (TCGA) database portal. The transcriptome data were taken from 390 colon cancer patients (172 LCC samples and 218 RCC samples); the somatic mutation data included 142 LCC samples and 187 RCC samples. We compared the expression and prognostic differences of LCC and RCC by conducting a multi-omics analysis of each using the clinical characteristics, immune microenvironment, transcriptomic differences, and mutation differences. The prognostic signatures was validated using the internal testing set, complete set, and external testing set (GSE39582). We also verified the independent prognostic value of the signature.

Results: The results of our clinical characteristic analysis showed that RCC had a significantly worse prognosis than LCC. The analysis of the immune microenvironment showed that immune infiltration was more common in RCC than LCC. The results of differential gene analysis showed that there were 360 differentially expressed genes, with 142 upregulated genes in LCC and 218 upregulated genes in RCC. The mutation frequency of RCC was generally higher than that of LCC. BRAF and KRAS gene mutations were the dominant genes mutations in RCC, and they had a strong mutual exclusion with APC, while APC gene mutation was the dominant gene mutation in LCC. This suggests that the molecular mechanisms of RCC and LCC differed. The 4-mRNA and 6-mRNA in the prognostic signatures of LCC and RCC, respectively, were highly predictive and may be used as independent prognostic factors.

Conclusion: The clinical classification of the anatomic subtypes of colon cancer is of great significance for early diagnosis and prognostic risk assessment. Our study provides directions for individualized treatment of left and right colon cancer.

Keywords: Gene expression; Immune microenvironment; Left-side colon cancer; Mutation; Prognosis; Right-side colon cancer.

Grants and funding

This work was supported by a grant from National Natural Science Foundation of China (nfsc:81560397 and 81660403). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.