Abstract
BackgroundColon 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.MethodsWe 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.ResultsThe 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.ConclusionThe 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.
Highlights
Colon cancer is one of the common tumors of digestive tract
The information of Light-side colon cancer (LCC) and Right-side colon cancer (RCC) in The Cancer Genome Atlas (TCGA) database and the chi-square test results of clinical characteristics can be seen in Table 1.After separating the data of LCC and RCC,we classified the data from the aspects of stage,T,N,M and age
The result prompted that RCC has a worse prognosis than LCC, which was manifested stage III-IV,T3-4, N1-2(Figure 1ad). there was no statistical difference between M1 and Age>65 subgroups, the survival rate of RCC was still worse than that of LCC(Figure 1e-f)
Summary
Colon cancer is one of the common tumors of digestive tract. Studies of left-side colon cancer(LCC) and right-side colon cancer(RCC) show that these two subtypes had different prognosis, outcomes, and clinical response to chemotherapy. It is necessary to explore the necessity of clinical classification of anatomic subtypes about colon cancer. It was widely believed that the accurate location of the tumor deserves no attention for the reason that the accurate location itself would not affect patients’ survival. In the past decade, the differences between LCC and RCC have received a great quantity of attention[2]. As we all known,the orgin of RCC comes from the midgut, which includes the cecum, ascending colon, and hepatic flexure. The orgin of LCC comes from the hindgut, which includes the splenic flexure, descending colon and sigmoid colon
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