Hsa_circ_0078607在结直肠癌组织及血清中的异常高表达及其临床意义

The aberrant overexpression of hsa_circ_0078607 in colorectal cancer tissues and serum and its clinical significance

目的:探究hsa_circ_0078607在结直肠癌组织和患者血清中的表达水平及其与结直肠癌患者临床病理特征的关系,评价其能否作为结直肠癌潜在的分子诊断标志物及治疗靶标。方法:收集2018年6月至2022年1月于柳州市人民医院胃肠外科接受结直肠癌切除手术患者的58对癌及癌旁组织标本,收集2020年1月至2022年12月于柳州市人民医院初次确诊的结直肠癌患者、结直肠息肉患者及健康人体检血清共152例;从结直肠癌差异表达circRNA谱中挑选特异性高表达的hsa_circ_0078607作为候选标志物,采用qPCR法检测其在结直肠癌细胞、组织、患者血清及结直肠息肉患者血清中的相对表达量,分析其与临床病理特征的关系。采用ROC曲线评估hsa_circ_0078607对结直肠癌及结直肠息肉的诊断价值。通过Circular RNA Interactome数据库预测与hsa_circ_0078607结合的miRNA,并用Cytoscape 3.9.1软件构建circRNA-miRNA-mRNA调控网络,同时通过GO/KEGG富集分析进一步了解其功能。结果:与癌旁组织或健康人血清相比,hsa_circ_0078607在结直肠癌细胞、组织和血清及息肉患者血清中呈高表达(P<0.001),其中有52例(89.7%)患者癌组织中表达上调,6例(10.3%)表达下调。结直肠癌组织中hsa_circ_0078607的相对表达量与肿瘤位置(P=0.029)、分化程度(P=0.046)和远处转移(P=0.043)有关联。ROC结果显示,在结直肠癌组织和血清中其诊断结直肠癌的AUC分别为0.8457[95%CI(0.7728,0.9186),P<0.0001]和0.8683[95%CI(0.7907,0.9459),P<0.0001];在息肉患者血清中,hsa_circ_0078607诊断结直肠息肉的AUC为0.7101[95%CI(0.6100,0.8101)]。GO/KEGG富集分析结果表明,hsa_circ_0078607下游的miRNA可能参与RNA聚合酶Ⅱ启动子转录调控、蛋白K48-连锁泛素化、Wnt、Hippo及MAPK信号通路调控等多个生物过程。结论:Hsa_circ_0078607在结直肠癌细胞、组织和血清中呈高表达,其在结直肠癌组织中的表达水平与肿瘤位置、分化程度和远处转移有关联,提示其可作为结直肠癌潜在的分子诊断标志物;其还可能介导结直肠癌的发生发展过程,对发现结直肠癌潜在的治疗靶点有重要意义。

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 paracancerous 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 circRNAmiRNA-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 0.8457(95%CI[0.7728,0.9186],P<0.0001)and 0.8683(95%CI[0.7907,0.9459],P<0.0001),respectively;and in the serum of colorectal polyp patients,the AUC of hsa_circ_0078607 for the diagnosis of colorectal polyps was 0.7101(95%CI[0.6100,0.8101]).GO/KEGG enrichment analysis results indicated that hsa_circ_0078607 downstream miRNAs may be involved in various biological processes,such as RNA polymeraseⅡpromoter 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.