组织circUBAP2对非小细胞肺癌的诊断和致癌作用的潜在价值分析-现代医学

组织circUBAP2对非小细胞肺癌的诊断和致癌作用的潜在价值分析

单位：文昌市人民医院心胸甲乳外科, 海南文昌 571300

分类号：R734.2

出版年·卷·期（页码）：2022·50·第七期（828-835）

摘要：

目的：分析组织环状RNA UBAP2（circUBAP2）与非小细胞肺癌（NSCLC）的诊断和致癌作用相关性。方法：收集2013年1月至2019年10月于本院行原发性肺癌根治性切除术的208例NSCLC患者的肿瘤组织标本和癌旁正常组织（距离手术切缘≥5 cm）标本。随机选择3对标本采用高通量测序技术（RNA-seq）检测组织标本中circRNAs差异性表达谱。采用实时荧光定量PCR法检测组织中circUBAP2相对表达量，采用Cox风险比例回归模型及Kaplan-Meier生存曲线分析circUBAP2表达对患者生存预后的预测价值。结果：经RNA-seq确定circUBAP2在NSCLC组织及其癌旁正常组织中存在差异性表达。在包含208例样本的整体研究中，NSCLC组织circUBAP2表达显著高于在癌旁正常组织（P<0.001），且N_1/2分期、癌胚抗原（CEA）水平≥6.6 ng·ml^-1、肿瘤最大直径<4.5 cm的NSCLC组织中circUBAP2表达水平更高（P<0.05）。Kaplan-Meier生存曲线显示，NSCLC组织circUBAP2高表达者及低表达者中位总生存期分别为17.50（9.65～63.85）个月和58.55（16.25～67.90）个月（Log-rank χ²=16.709，P<0.001）。单因素和多因素Cox回归分析显示，血清CEA水平和NSCLC组织中circUBAP2表达是患者总生存期的独立预后因子（P<0.001）。结论：circUBAP2可作为NSCLC诊断和预后的生物标志物之一。

Objective: To analyze the correlation between tissue circRNA UBAP2(circUBAP2) and the diagnosis and carcinogenesis of non-small cell lung cancer(NSCLC). Methods: Tumor tissue samples and paracancer normal tissue samples(≥ 5 cm from surgical margin) of NSCLC patients who underwent radical resection of primary lung cancer in our hospital from January 2013 to October 2019 were collected. RNA sequencing(RNA-seq) was used to detect the differential expression profile of circRNAs in tissue samples. The relative circUBAP2 expression in tissues was detected by quantitative real-time PCR, and Cox proportional hazards model, and Kaplan-Meier survivorship curve analyzed the prognostic value of circUBAP2 expression in patients.Results: RNA-seq determined the differential circUBAP2 expression in NSCLC tissues and adjacent normal tissues. In the overall study including 208 samples, circUBAP2 expression in NSCLC tissues was significantly higher than that in the normal adjacent tissues(P<0.001).And circUBAP2 expression level was higher in NSCLC tissues with N_1/2 stage, carcino-embryonic antigen(CEA) ≥ 6.6 ng·ml^-1 or tumor maximum diameter<4.5 cm(P<0.05). However, there was no significant correlation between the circUBAP2 relative expression and serum CEA level and the maximum tumor diameter in normal adjacent tissues(P>0.05).Kaplan-Meier survival curve was drawn for analysis, the median overall survival of the patients with high and low circUBAP2 expression in NSCLC tissues was 17.50(9.65-63.85) months and 58.55(16.25-67.90) months(Log-rank χ²=16.709, P<0.001), respectively.Univariate and multivariate Cox regression analysis showed that serum CEA level and circUBAP2 expression in NSCLC tissues were independent prognostic factors for overall survival(P<0.001). Conclusion: CircUBAP2 can be used as one of the emerging biomarkers for diagnosis and prognosis of NSCLC.

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