Prognostic role of STAT3 in solid tumors: a systematic review and meta-analysis

Abstract

Accumulated studies have provided controversial evidences of the association between signal transducer and activator of transcription proteins 3 (STAT3) expression and survival of human solid tumors. To address this inconsistency, we performed a meta-analysis with 63 studies identified from PubMed, Medline and EBSCO. We found STAT3 overexpression was significantly associated with worse 3-year overall survival (OS) (OR = 2.06, 95% CI = 1.57 to 2.71, P < 0.00001) and 5-year OS (OR = 2.00, 95% CI = 1.53 to 2.63, P < 0.00001) of human solid tumors. Similar results were observed when disease free survival (DFS) were analyzed. Subgroup analysis showed that elevated STAT3 expression was associated with poor prognosis of gastric cancer, lung cancer, gliomas, hepatic cancer, osteosarcoma, prostate cancer, pancreatic cancer but better prognosis of breast cancer. The correlation between STAT3 and survival of solid tumors was related to its phosphorylated state. High expression level of STAT3 was also associated with advanced tumor stage. In conclusion, elevated STAT3 expression is associated with poor survival in most solid tumors. STAT3 is a valuable biomarker for prognosis prediction and a promising therapeutic target in human solid tumors.

The ratio of STAT1 to STAT3 expression is a determinant of colorectal cancer growth

“…Indeed, tumor suppressive functions of STAT1 were associated with positive prognosis in CRC and breast cancer [14, 18, 19]. The role for STAT3 in carcinomas remains controversial - nuclear STAT3 (pYSTAT3) is regarded as a biomarker for prognosis prediction in solid tumours [20]. Several studies reported elevated and tumor promoting STAT3 signaling in CRC [5, 6, 7, 21].…”

STAT3 down‐regulation induces mitochondria‐dependent G2/M cell cycle arrest and apoptosis in oesophageal carcinoma cells

“…Under physiological conditions, STAT3 activation is transient and strictly regulated by upstream growth factor receptor tyrosine kinases and the cytoplasmic kinases, such as cytokine receptor‐associated Janus kinases (JAK) . A large body of evidence supports that STAT3 is persistently activated in a wide variety of human haematological and solid tumours, including leukaemia and cancers of the breast, melanoma, pancreas, prostate, colon and oesophageal cancers . Aberrant STAT3 activity promotes tumour growth, survival, invasion and metastasis through promotion of uncontrolled proliferation and angiogenesis, deregulation of cell cycle, and inhibition of apoptosis, thereby contributing to tumourigenic progression .…”

STAT3 inhibitor enhances chemotherapy drug efficacy by modulating mucin 1 expression in non-small cell lung carcinoma

“…A wide range of mechanisms is proposed for inappropriate STAT3 and MUC1 activation in cancer [24][25][26]. This increased knowledge of signaling pathways about tumor mechanisms could be translated into therapeutic strategies with less toxicity than current treatments.…”