Expression of activated signal transducer and activator of transcription-3 predicts poor prognosis in cervical squamous-cell carcinoma

Abstract

Background:Stat3 is a member of the Janus-activated kinase/STAT signalling pathway. It normally resides in the cytoplasm and can be activated through phosphorylation. Activated Stat3 (p-Stat3) translocates to the nucleus to activate the transcription of several molecules involved in cell survival and proliferation. The constitutive activation of Stat3 has been shown in various types of malignancies, and its expression has been reported to indicate a poor prognosis. However, the correlation between the constitutive activation of Stat3 and the prognosis of cervical cancer patients has not been reported.Methods:The immunohistochemical analysis of p-Stat3 expression was performed on tissues from 125 cervical squamous-cell carcinoma patients who underwent extended hysterectomy and pelvic lymphadenectomy, and the association of p-Stat3 expression with several clinicopathological factors and survival was investigated.Results:Positive p-Stat3 expression was observed in 71 of 125 (56.8%) cases and was significantly correlated with lymph node metastasis, lymph vascular space invasion, and large tumour diameter (>4 cm) by Fisher's exact test. Kaplan–Meier survival analysis showed that p-Stat3 expression was statistically indicative of a poor prognosis for overall survival (P=0.006) and disease-free survival (P=0.010) by log-rank test.Conclusion:These data showed that p-Stat3 expression in cervical cancer acts as a predictor of poor prognosis.

STAT3/IRF1 Pathway Activation Sensitizes Cervical Cancer Cells to Chemotherapeutic Drugs

“…Positive staining was mostly confined to the tumor borders adjacent to the stroma, suggesting a paracrine mode of STAT3 activation. In line with our results, another study found pTyr705-STAT3 in less than 10% of cells in most cervical cancer cases (34) and two previous studies detected pTyr705-STAT3 (35) or stronger nuclear STAT3 staining (36,37) in 22%-24% of cervical cancers. Only one group detected higher percentages of STAT3-phosphorylation in cervical cancers in an Indian population (38).…”

Chemotherapy Alters Monocyte Differentiation to Favor Generation of Cancer-Supporting M2 Macrophages in the Tumor Microenvironment

“…STATs represent central regulators of cancer-associated inflammation and influence interactions between cancer cells and their immune microenvironment that determine whether the inflammation promotes or inhibits cancer. The majority of gynecologic tumors have high STAT3 activity and this was associated with poor survival and chemoresistance (40). Interestingly, it has been reported that COX-2 is a transcriptional target of STAT3 signaling (41).…”

STAT3 rs3816769 polymorphism correlates with gene expression level and may predispose to nonsmall cell lung cancer: a preliminary study

“…As an important member of the STAT protein family, STAT3 participates in tumor cell survival, proliferation, migration, invasion, angiogenesis, and inhibition of apoptosis 12,13 in many types of human cancer, including lung cancer. [14][15][16][17][18][19][20][21] Moreover, the association between single nucleotide polymorphisms (SNPs) of STAT3 and susceptibility to carcinogenesis has been confirmed. 22,23 Additionally, it has been recognized that increased expression of STAT3 correlates with tumor progression and invasiveness; however, the causal mechanism of this molecular alteration and its prognostic value still remain unclear.…”