Expression and clinical correlates of signal transducers and activators of transcription 4: a tissue microarray study of 365 lung cancers

Background: Signal transducer and activator of transcription 4 (STAT4) is a transcription factor belonging to the signaling pathways of several cytokines. STAT4 has been studied in several malignancies; however, its clinical value in lung cancer has not been fully clarified. Hence, the objective of this study was to explore the expression and clinicopathological significance of STAT4 in lung cancer tissues. Methods: STAT4 expression was determined by immunohistochemistry (IHC) in tissue microarrays with 365 lung cancer and 30 normal lung tissues. The correlations with clinical parameters of STAT4 expression was analyzed by Receiver operating characteristic (ROC) curve. The correlation between STAT4 expression and clinicopathological parameters was further investigated. Results: STAT4 expression in lung cancer, including both non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), was all significantly higher than in non-cancerous normal lung (all P<0.05). ROC curve showed that the area under curve of STAT4 was 0.625 (95% CI 0.525 similar to 0.726, P=0.022) for lung cancer. In addition, STAT4 expression was associated to TNM stage (P=0.003), distal metastasis (P=0.007) and lymph node metastasis (P<0.001) in lung cancers. The consistent correlations between STAT4 and lymph node metastasis (P<0.001) and distal metastasis (P=0.006) were observed in NSCLC. Simultaneously, STAT4 expression was interrelated with clinical TNM stages (P=0.001) and lymph node metastasis (P=0.001) in SCLC. Conclusion: Our data demonstrated that STAT4 is upregulated in lung cancer. Higher STAT4 expression is associated with advanced stage and metastases, which indicates a potential tumorigenic role of STAT4 in the pathogenesis of lung cancer.