Integrated Analysis of ECT2 and COL17A1 as Potential Biomarkers for Pancreatic Cancer

Abstract

Background. Pancreatic cancer (PC) is a malignant tumor of the digestive tract. It presents with atypical clinical symptoms and lacks specific diagnostic indicators. This study is aimed at exploring the potential biomarkers of PC. Methods. TCGA database pancreatic cancer dataset was normalized and used to identify differentially expressed genes (DEGs). Survival, independent prognostic, and clinical correlation analyses were performed on DEGs to screen for key genes. DNA methylation, mutation, and copy number variation (CNV) analyses were used to analyze genetic variants in key genes. GSEA was performed to explore the functional enrichment of the key genes. Based on the expression of key genes, construction of a competing endogenous RNA (ceRNA) network, analysis of the tumor microenvironment (TME), and prediction of chemotherapeutic drug sensitivity were performed. Furthermore, the GEO database was used to validate the reliability of key genes. Results. Two key genes (ECT2 and COL17A1) were identified, which were highly expressed in PC. The mRNA expression of ECT2 and COL17A1 was associated with DNA methylation and CNV. The cell cycle, proteasome, and pathways in cancer were enriched in the high-COL17A1 and ECT2 groups. The TME results showed that immune scores were decreased in the high-ECT2 group. CeRNA network results showed that there were eleven miRNAs were involved in the regulation of ECT2 and COL17A1. Moreover, pRRophetic analysis showed that 20 chemotherapeutic drugs were associated with ECT2 and COL17A1 expression. Conclusions. Collectively, ECT2 and COL17A1 may be potential biomarkers for PC, providing a new direction for clinical diagnosis and treatment.

Identification of immune biomarkers associated with basement membranes in idiopathic pulmonary fibrosis and their pan-cancer analysis

“…Our study found that COL17A1 overexpression was related to poor prognosis of SKCM and PAAD. Studies have shown that COL17A1 is over-expressed in a variety of cancers (Thangavelu et al, 2016;Huang et al, 2022). In contrast, another study found that upregulation of COL17A1 expression was related to better prognosis in breast cancer (Yodsurang et al, 2017).…”

Copy Number Variations in Pancreatic Cancer: From Biological Significance to Clinical Utility

“…In another study aimed at exploring potential biomarkers of PDAC, analysis of transcriptomic and clinical data from The Cancer Genome Atlas Program (TCGA) revealed high expressions of the COL17A1 and ECT2 genes and associated this expression with CNVs [ 105 ]. The highly expressed genes of these patients were also related to the cell cycle and proteasome pathways.…”

“…Since several research studies have demonstrated the success of combining anti-PD-1 antibody immunotherapy with chemotherapy in treating PDAC [ 107 , 108 ], this study further demonstrated that the high-ECT2 group exhibited greater sensitivity towards anti-PD-1 therapy and 20 chemotherapeutic agents (e.g., bortezomib and rapamycin). These discoveries suggest that ECT2 and COL17A1 are potential diagnostic and prognostic markers for PDAC that can also facilitate innovative approaches for personalized treatment [ 105 ].…”

“…FHIT (3p14.2) and ATR (3q23) deletions were mostly reported in both sporadic familial cases, indicating their possible role in PDAC susceptibility as well as progression [ 77 , 110 , 118 , 133 , 136 ]. FHIT (3p14.2) deletions and ECT (3q26.31) amplifications have also been correlated with poor prognosis in PDAC [ 73 , 77 , 105 , 118 , 133 , 136 ].…”

Collagen XVII regulates tumor growth in pancreatic cancer through interaction with the tumor microenvironment

“…In addition to such skin diseases, altered expression of COL17A1 has been implicated in various types of solid cancer, and COL17A1 has been suggested as a potential diagnostic and prognostic biomarker for PAAD 11–13 . The role of COL17A1 in cancer progression, however, appears to be complex 8 .…”