J Cancer 2020; 11(7):1859-1868. doi:10.7150/jca.38798 This issue

Research Paper

Activated STAT3 Could Reduce Survival in Patients with Esophageal Squamous Cell Carcinoma by Up-regulating VEGF and Cyclin D1 Expression

Nan Zhang1, Min Zhang2, Zhou Wang3, Wei Gao4, Zhi-Gang Sun5✉

1. Department of Oncology, Jinan Central Hospital Affiliated to Shandong University; Jinan Central Hospital Affiliated to Shandong First Medical University; Jinan 250013, P.R. China.
2. Department of Dermatology, Jinan Central Hospital Affiliated to Shandong University; Jinan Central Hospital Affiliated to Shandong First Medical University; Jinan 250013, P.R. China.
3. Department of Thoracic Surgery, Provincial Hospital Affiliated to Shandong University, Jinan 250021, P.R. China.
4. Department of Pathology, Jinan Central Hospital Affiliated to Shandong University; Jinan Central Hospital Affiliated to Shandong First Medical University; Jinan 250013, P.R. China.
5. Department of Thoracic Surgery, Jinan Central Hospital Affiliated to Shandong University; Jinan Central Hospital Affiliated to Shandong First Medical University; Jinan 250013, P.R. China.

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Citation:
Zhang N, Zhang M, Wang Z, Gao W, Sun ZG. Activated STAT3 Could Reduce Survival in Patients with Esophageal Squamous Cell Carcinoma by Up-regulating VEGF and Cyclin D1 Expression. J Cancer 2020; 11(7):1859-1868. doi:10.7150/jca.38798. Available from https://www.jcancer.org/v11p1859.htm

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Abstract

Signal transduction and activators of transcription factor (STAT) 3 is associated with a poor prognosis in certain types of cancer. The purpose of the present study was to investigate the clinical and prognostic significance of STAT3/p-STAT3 expression in esophageal squamous cell cancer (ESCC) patients. A total of 71 patients were enrolled in the study. STAT3 and p-STAT3 expression were detected by Western Blot and immunohistochemistry assays. Stattic, the STAT3 inhibitor, was used to block the activation of STAT3 in ESCC cell lines Eca-109 and Kyse-30, and the CCK8 assay was performed to detect the effect of Stattic on the viability of ESCC cells. The expression of associated genes was assessed by RT-PCR and Western blot at RNA and protein levels, respectively. STAT3 expression was correlated with infiltration degree (pT) and pTNM. And p-STAT3 expression was correlated with pT, lymphatic metastasis (pN) and pTNM. The expression of VEGF, Bcl-xl and Cyclin D1 was up-regulated in ESCC tissues and positively correlated with p-STAT3 level, besides Bcl-xl. In vitro, Stattic inhibited the viability of Eca-109 and Kyse-30 cells in a dose- and time- dependent manner, and significantly inhibited the expression of VEGF, Bcl-xl and CyclinD1 at mRNA and protein level. The 5-year survival rate of the 71 patients was significantly associated with pT, pN, pTNM stage, p-STAT3 level, VEGF expression and Cyclin D1 expression. pN and p-STAT3 expression were independent relevant factors. Our results showed that p-STAT3 might serve as an essential biomarker for tumor invasion and metastasis in ESCC.

Keywords: STAT3, p-STAT3, Esophageal squamous cell cancer, Western Blot, Immunohistochemistry.