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

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.

The Impact of Patient Characteristics and Tumor Biology on the Accuracy of Preoperative Staging of Colon Cancer in Denmark. A Nationwide Cohort Study

“…Reactive lymph node enlargement in dMMR cancers is to be expected, because inability to repair mismatch results in accumulation of mutations, leading to the production of immune-response-eliciting proteins [18,19]. Additionally, there is a growing interest in regarding right-and left-sided cancers as distinct biological and clinical entities [20][21][22][23][24][25][26][27][28][29].…”

Development and validation of immune-related genomics nomogram for prognostic prediction in left- and right-side colorectal cancer

“…Immune, stromal, and ESTIMATE scores and tumor purity were calculated by the ESTIMATE package in R software based on Yoshihara et al (24). We also compared the expression levels of the human leukocyte antigen (HLA) gene family and immune check-point genes to explore the potential immunotherapy mechanism in LCC and RCC (25).…”

The Yin and Yang of Breast Cancer: Ion Channels as Determinants of Left–Right Functional Differences

“…For example, in animal studies using mouse models of BC, it was shown that L-R-sided tumors had distinct gene expression profiles [ 25 ]. In humans, recent studies discovered that L-R-sided tumors may respond differently to specific therapies depending on the local TME, with tumors in different regions of a single organ showing different expression profiles and properties [ 26 , 27 ]. Furthermore, L-sided BC was found to be associated with a more aggressive biology and a worse outcome as compared to R-BC [ 28 ].…”