Identification of GUCA2A and COL3A1 as prognostic biomarkers in colorectal cancer by integrating analysis of RNA-Seq data and qRT-PCR validation

Abstract

By 2030, it is anticipated that there will be 2.2 million new instances of colorectal cancer worldwide, along with 1.1 million yearly deaths. Therefore, it is critical to develop novel biomarkers that could help in CRC early detection. We performed an integrated analysis of four RNA-Seq data sets and TCGA datasets in this study to find novel biomarkers for diagnostic, prediction, and as potential therapeutic for this malignancy, as well as to determine the molecular mechanisms of CRC carcinogenesis. Four RNA-Seq datasets of colorectal cancer were downloaded from the Sequence Read Archive (SRA) database. The metaSeq package was used to integrate differentially expressed genes (DEGs). The protein–protein interaction (PPI) network of the DEGs was constructed using the string platform, and hub genes were identified using the cytoscape software. The gene ontology and KEGG pathway enrichment analysis were performed using enrichR package. Gene diagnostic sensitivity and its association to clinicopathological characteristics were demonstrated by statistical approaches. By using qRT-PCR, GUCA2A and COL3A1 were examined in colon cancer and rectal cancer. We identified 5037 differentially expressed genes, including (4752 upregulated, 285 downregulated) across the studies between CRC and normal tissues. Gene ontology and KEGG pathway analyses showed that the highest proportion of up-regulated DEGs was involved in RNA binding and RNA transport. Integral component of plasma membrane and mineral absorption pathways were identified as containing down-regulated DEGs. Similar expression patterns for GUCA2A and COL3A1 were seen in qRT-PCR and integrated RNA-Seq analysis. Additionally, this study demonstrated that GUCA2A and COL3A1 may play a significant role in the development of CRC.

Role and mechanism of COL3A1 in regulating the growth, metastasis, and drug sensitivity in cisplatin-resistant non-small cell lung cancer cells

“…Elevated COL3A1 expression has been found in various cancers, such as gastric cancer, esophageal cancer, and colorectal cancer, 7 , 9 , 26 which highlights the potential role of COL3A1 as a promising predictor for these diseases prognosis. In view of function, knocking down COL3A1 can lead to a potent repression of gastric tumorigenesis 27 ; COL3A1 downregulation is able to hinder breast cancer cell growth and invasiveness through PD-L1 11 ; inhibition of COL3A1 also impedes xenograft tumor growth and metastasis in esophageal squamous cell carcinoma.…”

“… 7 COL3A1 is also identified as a promising independent predictor for prognosis of head and neck cancer and colorectal cancer. 8 , 9 Abnormal expression of COL3A1 mediated by RNF185 exhibits a potent regulatory activity in the metastatic potential of prostate cancer. 10 Moreover, in triple negative breast cancer, knocking down COL3A1 plays a repressive role in cancer cell growth and metastasis depending on PD-L1 reduction.…”

Elucidating the role of angiogenesis-related genes in colorectal cancer: a multi-omics analysis

“…Research has demonstrated that COL3A1 is selectively expressed by the microvasculature in brain tumors ( 36 ). Existing evidence indicates that COL3A1 exhibits higher expression in CRC tissues compared to control tissues and is associated with CRC metastasis ( 37 – 39 ). TIMP1, reported to be a multi-faceted biomarker in CRC, can function as a diagnostic biomarker for CRC and is linked to the immunological microenvironment, drug sensitivity, and inhibition of ferroptosis ( 40 ).…”