PEG3、STMN1基因在非小细胞肺癌的表达及其与临床病理特征、血管生成相关性研究

Expression of PEG3 and STMN1 genes in non-small cell lung cancer and their association with clinicopathological features and angiogenesis

摘要:

目的 探讨父系表达基因3（PEG3）、抑微管装配蛋白1（STMN1）基因在非小细胞肺癌（NSCLC）的表达及其与临床病理特征和血管生成的关系。方法 收集宁夏医科大学总医院肿瘤医院2021年1月—2023年1月经病理证实的96例NSCLC患者癌组织及癌旁组织，采用实时荧光定量聚合酶链反应（qRT-PCR）检测和免疫组织化学检测癌组织与癌旁组织PEG3、STMN1、VEGF及CD105 mRNA的表达；比较不同临床病理特征NSCLC患者癌组织PEG3、STMN1的阳性表达率；采用Pearson法分析PEG3、STMN1与VEGF及CD105关系；采用受试者工作特征（ROC）曲线分析PEG3、STMN1对NSCLC的诊断价值。结果 与癌旁组织比较，PEG3在NSCLC组织中表达降低（P <0.05），STMN1、VEGF及CD105在NSCLC组织中表达升高（P <0.05）；NSCLC组织中STMN1、VEGF及CD105阳性率分别为62.50%、69.79%和72.92%，分别高于癌旁组织5.21%、10.42%和13.54% （P <0.05），NSCLC组织中PEG3阳性率为8.33%低于癌旁组织73.96%（P <0.05）；不同年龄、性别及肿瘤类型NSCLC患者的PEG3及STMN1表达水平比较，差异无统计学意义（P >0.05），不同TNM分期、淋巴结转移及分化程度NSCLC患者的PEG3及STMN1表达水平比较，差异有统计学意义（P <0.05）；NSCLC组织的PEG3与STMN1、VEGF及CD105均呈负相关（P <0.05），NSCLC组织的STMN1与PEG3呈负相关（P <0.05），与VEGF及CD105均呈正相关（P <0.05）；PEG3诊断NSCLC的曲线下面积为0.750（95% CI：0.453，0.936）、敏感性为73.66%（95% CI：0.650，0.937）、特异性为79.62%（95% CI：0.590，0.956）；STMN1诊断NSCLC的曲线下面积为0.796（95% CI：0.540，0.942）、敏感性为80.30%（95% CI：0.744，0.978）、特异性为81.12%（95% CI：0.612，0.996）；PEG3+STMN1联合诊断的曲线下面积为0.935（95% CI：0.753，0.995）、敏感性为92.33%（95% CI：0.751，0.930）、特异性为77.12%（95% CI：0.735，0.948）。结论 NSCLC组织PEG3降低、STMN1升高，与肺癌TNM分期、分化程度相关，其可以加快肿瘤血管生成，能够一定程度提高疾病诊断价值。

Abstract:

Objective To investigate the expression of Paternally Expressed Gene 3 (PEG3) and Stathmin 1 (STMN1) in non-small cell lung cancer (NSCLC) and their correlation with clinicopathological features and angiogenesis.Methods A total of 96 NSCLC patients diagnosed by pathology from January 2021 to January 2023 at the General Hospital of Ningxia Medical University were included. cancerous and adjacent non-cancerous tissues were collected for real-time quantitative PCR (qRT-PCR) and immunohistochemistry to assess the expression of PEG3, STMN1, VEGF, and CD105 mRNA. The positive expression rates of PEG3 and STMN1 in NSCLC tissues with different clinicopathological characteristics were compared. Pearson correlation analysis was used to assess the relationships between PEG3, STMN1, VEGF, and CD105. Receiver operating characteristic (ROC) curves analyzed the diagnostic value of PEG3 and STMN1 for NSCLC.Results Compared with adjacent non-cancerous tissues, PEG3 expression was decreased in NSCLC tissues (P <0.05), whereas STMN1, VEGF, and CD105 expressions were increased (P <0.05). Positive rates of STMN1, VEGF, and CD105 in NSCLC tissues were 62.50%, 69.79%, and 72.92%, respectively, significantly higher than in adjacent tissues (P <0.05), whereas the positive rate of PEG3 was 8.33%, significantly lower than in adjacent tissues (73.96%, P <0.05). No significant differences were found in the expression levels of PEG3 and STMN1 across different ages, genders, and tumor types (P >0.05), while significant differences were observed in different TNM stages, lymph node metastasis statuses, and differentiation degrees (P <0.05). PEG3 showed a negative correlation with STMN1, VEGF, and CD105 in NSCLC tissues (P <0.05). STMN1 was negatively correlated with PEG3 (P <0.05) and positively correlated with VEGF and CD105 (P <0.05). The area under the curve (AUC) for diagnosing NSCLC using PEG3 was 0.750 (95% CI: 0.453, 0.936) with a sensitivity of 73.66% (95% CI: 0.650, 0.937) and a specificity of 79.62% (95% CI: 0.590, 0.956); for STMN1, the AUC was 0.796 (95% CI: 0.540, 0.942) with a sensitivity of 80.30% (95% CI: 0.744, 0.978) and a specificity of 81.12% (95% CI: 0.612, 0.996). The combined diagnosis of PEG3+STMN1 had an AUC of 0.935 (95% CI: 0.753, 0.995), with a sensitivity of 92.33% (95% CI: 0.751, 0.930) and a specificity of 77.12% (95% CI: 0.735, 0.948).Conclusion The decreased expression of PEG3 and increased expression of STMN1 in NSCLC tissues are associated with tumor TNM stage and differentiation degree, correlating with enhanced tumor angiogenesis and improving diagnostic accuracy to some extent.