The aberrant overexpression of hsa_circ_0078607 in colorectal cancer tissues and serum and its clinical significance
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Abstract:
Objective: To investigate the expression level of hsa_circ_0078607 in colorectal cancer tissues and patients’ serum, and its correlation with clinicopathological characteristics of colorectal cancer patients, and to evaluate whether it can be used as a potential molecular diagnostic marker and therapeutic target for colorectal cancer. Methods: 58 pairs of colorectal cancer tissue and para-cancerous tissue specimens were collected from patients undergoing colorectal cancer resection surgery in the Department of Gastrointestinal Surgery of Liuzhou People's Hospital between June 2018 and January 2022. The serum of 152 colorectal cancer patients and colorectal polyp patients first diagnosed in Liuzhou People's Hospital between January 2020 and December 2022 and physical examination personnel was collected. The specifically highly expressed hsa_circ_0078607 was selected from the differentially expressed circRNAs profile of colorectal cancer as a candidate marker, qPCR was used to detect its relative expression levels in colorectal cancer cell lines, tissues and serum and the serum of colorectal polyp patients, and analyze its correlation with clinicopathological characteristics. The diagnostic value of hsa_circ_0078607 for colorectal cancer and colorectal polyp was evaluated by ROC curve. The miRNA binding to hsa_circ_0078607 was predicted by Circular RNA Interactome database, and the circRNA-miRNA-mRNA regulatory network was constructed by Cytoscape 3.9.1 software. At the same time, GO/KEGG enrichment analysis was used to further understand its function. Results: Compared with paracancerous tissue or serum from healthy people, hsa_circ_ 0078607 was highly expressed in colorectal cancer cells, tissues and serum and the serum of colorectal polyp patients (P<0.001). Its expression was up-regulated in the cancer tissues of 52 patients (89.7%), and was down-regulated in 6 patients (10.3%). The relative expression of hsa_circ_0078607 in colorectal cancer tissues was correlated with tumor location (P=0.029), degree of differentiation (P=0.046) and distant metastasis (P=0.043). The ROC results showed that the AUC of hsa_circ_0078607 for the diagnosis of colorectal cancer in tissue and serum was 0.845 7 (95%CI [0.772 8, 0.918 6], P<0.000 1) and 0.8683 (95%CI [0.790 7, 0.945 9], P<0.000 1), respectively; and in the serum of colorectal polyp patients, the AUC of hsa_circ_0078607 for the diagnosis of colorectal polyps was 0.710 1 (95%CI [0.610 0, 0.810 1]). GO/KEGG enrichment analysis results indicated that hsa_circ_0078607 downstream miRNAs may be involved in various biological processes, such as RNA polymerase Ⅱ promoter transcription regulation, protein K48-linked ubiquitination, Wnt, Hippo, and MAPK signaling pathway regulation. Conclusion: Hsa_circ_0078607 is highly expressed in colorectal cancer cells, tissues and serum, and its expression level in colorectal cancer tissues is correlated with tumor location, degree of differentiation and distant metastasis, suggesting that it can be used as a potential molecular diagnostic marker for colorectal cancer. At the same time, it may also mediate the occurrence and development of colorectal cancer, which is of great significance for discovering potential therapeutic targets of colorectal cancer.