Pathologic evolution-related Gene Analysis based on both single-cell and bulk transcriptomics in Colorectal Cancer

Abstract

Purpose: The patients diagnosed with colorectal cancer (CRC) are likely to undergo differential outcomes in clinical survival owing to different pathologic stages. However, signatures in association with pathologic evolution and CRC prognosis are not clearly defined. This study aimed to identify pathologic evolution-related genes in CRC based on both single-cell and bulk transcriptomics. Patients and methods: The CRC single-cell transcriptomic dataset (GSE81861, n=590) with clinical information and tumor microenvironmental tissues was collected to identify the pathologic evolution-related genes. The colonic adenocarcinoma and rectum adenocarcinoma transcriptomics from The Cancer Genome Atlas were obtained as the training dataset (n=363) and 5 other CRC transcriptomics cohorts from Gene Expression Omnibus (n=1031) were acquired as validation data. Graph-based clustering analysis algorithm was applied to identify pathologic evolution-related cell populations. Pseudotime analysis was performed to construct the trajectory plot of pathologic evolution and to define hub genes in the evolution process. Cell-type identification by estimating relative subsets of RNA transcripts was then executed to build a novel cell infiltration classifier. The prediction efficacy of this classifier was validated in bulk transcriptomic datasets. Results: Epithelial and T cells were elucidated to be related to the pathologic stages in CRC tissues. Pseudotime analysis and survival analysis indicated that HOXC5, HOXC8 and BMP5 were the marker genes in pathologic evolution process. Our cell infiltration classifier exhibited excellent forecast efficacy in predicting pathologic stages and prognosis of CRC patients. Conclusion: We identified pathologic evolution-related genes in single-cell transcriptomic and proposed a novel specific cell infiltration classifier to forecast the prognosis of CRC patients based on pathologic stage-related hub genes HOXC6, HOXC8 and BMP5.

Action of m6A-related gene signatures on the prognosis and immune microenvironment of colonic adenocarcinoma

“…[ 45 , 46 ] HOXC6 encodes a highly conserved transcription factor, and multivariate analysis showed that increased HOXC6 expression was an independent risk factor for poor prognosis in CRC patients [ 47 ]. HOXC6 is considered as a marker gene in the pathological evolution of CRC and can be used to predict the prognosis of CRC patients [ 48 ]. Our results also showed that COAD patients with high HOXC6 expression had a lower survival rate.…”

Exosomal‐miR‐522‐3p derived from cancer‐associated fibroblasts accelerates tumor metastasis and angiogenesis via repression bone morphogenetic protein 5 in colorectal cancer

“…44 Li et al reported BMP5 was a biomarker in the pathologic evolution process, which was able to be used in the prediction of pathologic stages and prognosis. 45 Nevertheless, the detailed regulatory mechanism of BMP5 remains elusive. BMP5 is an important member of the TGF-β superfamily, which could involve in a series of regulation of cell phenotypes by BMP/SMAD signaling.…”

“…Li et al . reported BMP5 was a biomarker in the pathologic evolution process, which was able to be used in the prediction of pathologic stages and prognosis 45 . Nevertheless, the detailed regulatory mechanism of BMP5 remains elusive.…”

Cancer Risk Score Prediction Based on a Single-Nucleotide Polymorphism Network

“…In a recent study, HOXC6 was found to be excessively expressed in colorectal cancer tissues; that study also indicated that higher HOXC6 expression was associated with poorer overall survival [ 26 ]. HOXC6 has been included in several prognostic risk models as a signature gene [ 27 ]. Qi et al [ 28 ] utilized public RNA and mRNA sequencing data from The Cancer Genome Atlas database to analyze the expression of HOXC6 in colorectal cancer in relation to the tumor immune microenvironment (TIME).…”