Yang Mengqi, Chen Huanting, Zhou Lin, Chen Kai, Su Fengxi
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University Guangzhou, China.
Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University Guangzhou, China.
Am J Transl Res. 2019 Aug 15;11(8):4866-4880. eCollection 2019.
Non-small cell lung cancer (NSCLC) is a highly malignant type of cancer with a poor 5-year survival rate. The development of prognostic biomarkers and novel drug targets are required in order to improve the survival for NSCLC patients. Signal transducer and activator of transcription (STAT) proteins are cytoplasmic transcription factors known to play key roles in many cellular biological processes. However, the roles of STAT family members in the development and progression of NSCLC have not yet been apparently determined. Our study investigated the roles of STATs in the prognosis of NSCLC using cBioPortal, Human Protein Atlas, ONCOMINE, and Kaplan-Meier Plotter databases. High mutation rate of STATs existed in both lung adenocarcinoma (ADE) patients and squamous cell carcinoma (SCC) patients. High mRNA expression of STAT2 was significantly associated with shorter overall survival (OS) in NSCLC patients, while increased STAT5 and STAT6 were associated with better OS in NSCLC patients. We further found that increased mRNA expressions of STAT2 and STAT3 predicted unfavorable overall survival (OS) while high mRNA expression of STAT5B and STAT6 related to favorable OS for lung ADE patients. However, no significant correlation was identified for lung SCC patients. In stratified survival analysis, high expression of STAT2 predicted poor prognosis in stage II NSLCC patients, surgical margins negative patients and female patients. Taken together, our results illustrated that STAT5B and STAT6 could be effective prognostic biomarkers for survivals of NSCLC patients. And STAT2 might be a promising therapeutic target for the treatment of NSCLC as well as ADE.
非小细胞肺癌（NSCLC）是一种高度恶性的癌症，5年生存率较低。为了提高NSCLC患者的生存率，需要开发预后生物标志物和新型药物靶点。信号转导和转录激活因子（STAT）蛋白是已知在许多细胞生物学过程中起关键作用的细胞质转录因子。然而，STAT家族成员在NSCLC发生发展中的作用尚未明确确定。我们的研究使用cBioPortal、人类蛋白质图谱、ONCOMINE和Kaplan-Meier Plotter数据库研究了STATs在NSCLC预后中的作用。肺腺癌（ADE）患者和肺鳞状细胞癌（SCC）患者中均存在较高的STATs突变率。STAT2的高mRNA表达与NSCLC患者较短的总生存期（OS）显著相关，而STAT5和STAT6的增加与NSCLC患者较好的OS相关。我们进一步发现，STAT2和STAT3的mRNA表达增加预示着不良的总生存期（OS），而STAT5B和STAT6的高mRNA表达与肺ADE患者的良好OS相关。然而，对于肺SCC患者未发现显著相关性。在分层生存分析中，STAT2的高表达预示着II期NSLCC患者、手术切缘阴性患者和女性患者的预后不良。综上所述，我们的结果表明，STAT5B和STAT6可能是NSCLC患者生存的有效预后生物标志物。并且STAT2可能也是治疗NSCLC以及ADE的有前景的治疗靶点。
