Sirtuin2 correlates with lymph node metastasis, increased FIGO stage, worse overall survival, and reduced chemosensitivity to cisplatin and paclitaxel in endometrial cancer.

Abstract

This study aimed to investigate the correlation of sirtuin2 (SIRT2) with clinical characteristics, prognosis in endometrial cancer (EC) patients, and its effect on chemosensitivity in EC cell lines. A total of 137 EC patients who underwent surgical resection were retrospectively enrolled. SIRT2 expression in tumor tissues (n = 137) and adjacent tissues (n = 61) was detected by immunohistochemistry (IHC) staining and evaluated by a semiquantitative scoring method. EC patients' clinical characteristics and survival data were collected. Besides, SIRT2 was modulated by plasmid transfection in EC cells, then their chemosensitivity to cisplatin and paclitaxel was evaluated. SIRT2 was increased in tumor tissues compared with adjacent tissues (reflected by both IHC score and high-expression ratio, both P < 0.001). Meanwhile, tumor SIRT2 was positively correlated with lymph node metastasis (P = 0.037) and the International Federation of Gynecology and Obstetrics (FIGO) stage (P = 0.044), but not other clinical characteristics. Moreover, tumor SIRT2 high expression was correlated with worse overall survival (OS) (P = 0.023), while it could not independently predict OS (P = 0.090, hazard ratio = 2.782). Besides, both mRNA and protein levels of SIRT2 were increased in Ishikawa (P = 0.035) and KLE (P < 0.001) cells compared with human endometrial epithelial cells. SIRT2 overexpression decreased chemosensitivity to cisplatin and paclitaxel in Ishikawa cells, while SIRT2 knockdown increased chemosensitivity to cisplatin and paclitaxel in KLE cells (all P < 0.05). SIRT2 correlates with lymph node metastasis, increased FIGO stage, worse OS, and reduced chemosensitivity to cisplatin and paclitaxel in EC.