Abstract
BackgroundThe identification of novel functional biomarkers is essential for recognizing high-risk patients, predicting recurrence, and searching for appropriate treatment. However, no prognostic biomarker has been applied for colorectal cancer (CRC) in the clinic.MethodsIntegrated with transcriptomic data from public databases, multi-omics examinations were conducted to search prognostic biomarkers for CRC. Moreover, the potential biological functions and regulatory mechanism of these predictive genes were also explored.ResultsIn this study, we revealed that three mitochondrial genes were associated with the poor prognosis of CRC. Integrated analyses of transcriptome and proteome of CRC patients disclosed numerous down-regulated mitochondrial genes at both mRNA and protein levels, suggesting a vital role of mitochondria in carcinogenesis. Combined with the bioinformatics studies of transcriptomic datasets of 538 CRC patients, three mitochondrial prognostic genes were eventually selected out, including HIGD1A, SUCLG2, and SLC25A24. The expression of HIGD1A exhibited a significant reduction in two subtypes of adenoma and six subtypes of CRC, while the down-regulation of SUCLG2 and SLC25A24 showed more advantages in rectal mucinous adenocarcinoma. Moreover, we unveiled that these three genes had common expressions and might collaboratively participate in the synthesis of ribosomes. Our original multi-omics datasets, including DNA methylation, structural variants, chromatin accessibility, and phosphoproteome, further depicted the altered modifications on their potential transcriptional factors.ConclusionsIn summary, HIGD1A, SUCLG2, and SLC25A24 might serve as predictive biomarkers for CRC. The biological activities they involved in and their upstream regulators we uncovered would provide a functional context for the further-in-depth mechanism study.Graphic abstract
Highlights
The identification of novel functional biomarkers is essential for recognizing high-risk patients, predicting recurrence, and searching for appropriate treatment
We investigated if these expression changes in colorectal cancer (CRC) tissues versus normal adjacent tissues were occurring at the transcriptional level
After overlapping the 5482 down-regulated mRNA in CRC, and 598 down-regulated proteins in CRC, and the independent prognostic factors (IPFs), we discovered that the expression of six IPFs were both changed at the mRNA and protein levels (Fig. 1f ), in which three candidates
Summary
The identification of novel functional biomarkers is essential for recognizing high-risk patients, predicting recurrence, and searching for appropriate treatment. Colorectal cancer (CRC) is the fourth leading cause of all cancer mortality. It kills nearly 900,000 people a year and accounts for 10% of cancer-inducing deaths [1]. It is necessary to search for effective predictive biomarkers to identify high-risk patients and develop appropriate treatment strategies to improve their prognosis. Some studies have identified several mitochondrial genes as potential prognostic biomarkers. Most studies lack a large-sample cohort, or rarely compare the genes expression between various subtypes of CRC, or the biomarkers have higher correlations with other tumors [12,13,14,15,16], which means more work still need to be done before clinical application
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