MTAP deficiency is associated with an unfavourable prognosis and platinum resistance in ovarian cancer

作者：Ding, Nan; Yin, Fuqiang; Deng, Xihan; Feng, Liyuan; Wei, Luwei; Huang, Yongzhi; Liang, Zhenxin; Zhang, Wei; Li, Li^*

来源：International Journal of Clinical and Experimental Pathology, 2017, 10(2): 1122-1130.

• Ovarian cancer
• methylthioadenosine phosphorylase
• prognosis
• platinum resistance
• biomarker

Methylthioadenosine phosphorylase (MTAP), a key enzyme of adenosine salvage pathway, has been reported to be high frequency absence or reduced in various human tumors. This study was to investigate the expression of MTAP in ovarian cancer (OC) and the association with platinum based chemotherapy response and prognosis. We first examined the expression of MTAP in OC cell lines and 20 OC tissues. Then we retrieved the expression of MTAP in 90 platinum-resistant and 197 platinum-sensitive ovarian cancers, according to The Cancer Genome Atlas (TCGA) Ovarian Statistics data. Further, the association between MTAP and drug resistance in OC was analyzed by bioinformatic analysis. Last, Kaplan-Meier plotter (KM plotter), was invited to validate the MTAP's prognostic value in OC, Kaplan-Meier survival plot and P value were calculated. Compared with the parental OC cell lines, low expression of MTAP was found in platinum-resistant cell lines: A2780/DDP (P=0.021), A2780/CBP (P=0.002) and SKOV3/DDP (P=0.008). Similarly, MTAP's down-expression was also found between 10 platinum-resistant and 10 platinum-sensitive tissues (P=0.003). Running data from TCGA, MTAP in platinum-resistant group was down expressed compared with platinum-sensitive group (P=0.024). Bioinformatic process showed close relationship between MTAP and drug resistance. Computed by KM plotter, low expression of MTAP was associated with OC patients' poor progression-free survival (P=0.027) and overall survival (P=0.0033). These data demonstrate that low expression of MTAP is associated with platinum based chemotherapy resistance and worse prognosis in OC. Taken together these findings suggest that MTAP could serve as a potential biomarker for prognosis and predictor for platinum based chemotherapy response in OC.

• 出版日期2017
• 单位广西医科大学