He Zhengfei, Zhang Xiaochun, Wang Shanshan, Dai Xiaojun, Wang Qingying, Lu Qingyun, Lu Haiyan, Wu Yongjian, Wang Hui, Wang Xuemei, Wang Haibo, Liu Yanqing
Yangzhou Hospital Affiliated to Nanjing University of Chinese Medicine, Nanjing University of Chinese Medicine, Yangzhou 225002, China.
Yangzhou Hospital of Traditional Chinese Medicine, Yangzhou 225002, China.
Heliyon. 2023 May 12;9(5):e16150. doi: 10.1016/j.heliyon.2023.e16150. eCollection 2023 May.
Signal transducers and activators of transcription (STAT) proteins, well-known cytoplasmic transcription factors, were found to be abnormally expressed in various cancers and play essential parts in the initiation, progression and therapy resistance of cancer. Nevertheless, the functions of different STATs in pancreatic cancer (PC) and their relationship to the prognosis and immune infiltration as well as drug efficacy in PC patients have not been systematically elucidated.
Expression, prognosis, genetic alterations and pathway enrichment analyses of the STAT family were investigated via Oncomine, GEPIA, Kaplan Meier-plotter, cBioPortal, Metascape and GSEA. Analysis of tumor immune microenvironment was conducted by ESTIMATE and TIMER. "pRRophetic" packages were used for analysis of chemotherapeutic response. Finally, the diagnostic and prognostic value of key STATs were further validated through public datasets and immunohistochemistry.
In this study, only STAT1 mRNA level was significantly increased in tumor tissues and highly expressed in PC cell lines via multiple datasets. PC patients with higher STAT1/4/6 expression had a worse overall survival (OS) and progression-free survival (PFS), while higher STAT5B expression was correlated with better prognosis in the TCGA cohort. The STATs-associated genes were enriched in pathways about the remodeling of tumor immune microenvironment. The STATs levels were significantly correlated with immune infiltration, except STAT6. The STAT1 was identified as a potential biomarker and its diagnostic and prognostic value were further validated at mRNA and protein levels. GSEA showed that STAT1 may be involved in the progression and immune regulations of PC. Moreover, STAT1 expression was significantly related to the level of immune checkpoint, and predicted immunotherapy and chemotherapy responses.
STAT family members were comprehensively analyzed and STAT1 was identified as an effective biomarker for predicting the survival and therapeutic response, which could be beneficial to develop better treatment strategies.
信号转导子和转录激活子（STAT）蛋白是著名的细胞质转录因子，被发现在各种癌症中异常表达，并在癌症的发生、发展及治疗耐药中发挥重要作用。然而，不同STATs在胰腺癌（PC）中的功能及其与PC患者预后、免疫浸润以及药物疗效的关系尚未得到系统阐明。
通过Oncomine、GEPIA、Kaplan Meier-plotter、cBioPortal、Metascape和GSEA对STAT家族进行表达、预后、基因改变及通路富集分析。利用ESTIMATE和TIMER进行肿瘤免疫微环境分析。使用“pRRophetic”软件包分析化疗反应。最后，通过公共数据集和免疫组织化学进一步验证关键STATs的诊断和预后价值。
在本研究中，通过多个数据集发现肿瘤组织中仅STAT1 mRNA水平显著升高，且在PC细胞系中高表达。在TCGA队列中，STAT1/4/6表达较高的PC患者总生存期（OS）和无进展生存期（PFS）较差，而STAT5B表达较高与较好的预后相关。与STATs相关的基因富集于肿瘤免疫微环境重塑相关通路。除STAT6外，STATs水平与免疫浸润显著相关。STAT1被确定为潜在生物标志物，其诊断和预后价值在mRNA和蛋白质水平上得到进一步验证。GSEA显示STAT1可能参与PC的进展和免疫调节。此外，STAT1表达与免疫检查点水平显著相关，并可预测免疫治疗和化疗反应。
对STAT家族成员进行了全面分析，确定STAT1为预测生存和治疗反应的有效生物标志物，这可能有助于制定更好的治疗策略。
