Analysis of prognosis, genome, microbiome, and microbial metabolome in different sites of colorectal cancer

Abstract

Background: The colorectum includes ascending colon, transverse colon, descending colon, sigmoid colon, and rectum. Different sites of colorectal cancer (CRC) are different in many aspects, including clinical symptoms, biological behaviour, and prognosis. Purpose: This study aimed to analyse prognosis, genes, bacteria, fungi, and microbial metabolome in different sites of CRC. Methods: The Surveillance, Epidemiology, and End Results (SEER) database and STAT were used to statistically describe and analyse the prognosis in different sites of CRC. RNA sequences of CRC from Broad Institute's GDAC Firehose were re-annotated and reanalysed based on different sites using weighted gene co-expression network analysis (WGCNA). The Kaplan-Meier method was used to analyse the prognosis and Cytoscape was used to construct a drugtarget network based on DGIdb databases. Bacterial 16S V3-V4 and fungal ITS V3-V4 ribosomal RNA genes of stool samples were sequenced. Gas chromatography/mass spectrometry (GS/MS) was performed to detect the microbial metabolites in stool samples. Bioinformatics analysis was performed to compare distinct gut microorganisms and microbial metabolites between rectal and sigmoid cancers. Results: The prognosis in CRC with different sites is significantly different. The closer to the anus predicted longer survival time. The difference between genes and co-expression pairs in CRC with different sites were constructed. The relative abundance of 112 mRNAs and 26 lncRNAs correlated with the sites of CRC were listed. Nine differentially expressed genes at different sites of CRC were correlated with prognosis. A drug-gene interaction network contained 227 drug-gene pairs were built. The relative abundance of gut bacteria and gut fungus, and the content of microberelated metabolites were statistically different between rectal and sigmoid cancers. Conclusions: There are many differences in prognosis, genome, drug targets, gut microbiome, and microbial metabolome in different colorectal cancer sites. These findings may improve our understanding of the role of the CRC sites in personalized and precision medicine.

Evaluation of Prognostic Factors for Survival in Transverse Colon Cancer

“…Most published studies have used to consider TCC as part of the RCC, although tumors arising from the transverse colon, according to its embryological origins, may share characteristics with right colon cancer (RCC) as well as with left colon cancer (LCC) [1,[15][16][17]. Thus, it is still not completely clear if TCC behavior is more like to right-sided rather than left-sided ones or if it has its clinicopathological features and a different clinical outcome.…”

<p>Progress in Research on Colorectal Cancer-Related Microorganisms and Metabolites</p>

“…42 Our previous study also demonstrated that the levels of SCFAs in CRC patients and individuals with a high risk of CRC were higher than those in healthy individuals. 8…”

“…6 Recent studies have shown that changes in the gut microbiota could be a major factor to trigger CRC. 7,8 There are many types and numbers of microorganisms in the intestinal tract. They can participate in the substitution of sugar, protein, starch, vitamins, and other nutrients to determine the body's immune function and maintain the health of the host.…”

Tumour Microbiome-Based Subtypes of Colorectal Cancer Correlate with Clinical Variables

“…We can only speculate whether the prolonged exposure of tumour mucosa to predominantly stool bacteria that is mechanistically related to tumours in distant part of the colon (left-sided or with onset in rectosigmoid and rectum) can have potentially harmful or bene cial effects or whether any associations are mostly due to the well-known molecular differences in the right vs left sided tumours [32,63,94].…”