Upregulation of PD-L1 and APE1 is associated with tumorigenesis and poor prognosis of gastric cancer.
Upregulation of PD-L1 and APE1 is associated with tumorigenesis and poor prognosis of gastric cancer.
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DOI：
10.2147/dddt.s75152
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Wang D
中科院分区：
文献类型：
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作者：
Qing Y;Li Q;Ren T;Xia W;Peng Y;Liu GL;Luo H;Yang YX;Dai XY;Zhou SF;Wang D
胃癌是一种致命性恶性肿瘤，发病率呈上升趋势。目前尚无有效的方法对胃癌进行早期诊断、监测转移和预后。在本研究中，我们检测了程序性死亡配体-1(PD-L1)和脱嘌呤/脱嘧啶核酸内切酶1(APE1)的表达与胃癌预后的关系。应用免疫组织化学方法检测107例人胃癌组织中PD-L1和APE1的表达。用SPSS19.0统计软件分析PD-L1和APE1的表达与胃癌临床病理特征的关系。PD-L1和APE1在胃癌组织中的阳性表达率分别为50.5%(54/107)和86.9%(93/107)。PD-L1和APE1的阳性表达与肿瘤的侵袭深度、淋巴结转移、病理类型、总生存期和较高T分期有关。此外，PD-L1在高分化胃癌中的表达高于低分化胃癌(P=0.008)。此外，APE1和PD-L1在胃癌组织中的表达呈正相关(r=0.336，P<0.01)。多因素分析显示，肿瘤侵袭深度是影响预后的重要因素(危险度比为19.91；P=0.000)，而与PD-L1、APE1值、预后等指标无明显相关性。PD-L1和APE1基因表达异常可能与胃癌的发生发展和预后不良有关。提示PD-L1和APE1的高表达是胃癌的危险因素，是预测胃癌预后的新的生物标志物。此外，我们的研究结果表明，靶向PD-L1和APE1信号通路可能成为肿瘤免疫治疗和胃癌靶向治疗的新策略，尤其是在有深度侵袭和淋巴结转移的患者中。
Gastric cancer is a fatal malignancy with a rising incidence rate. Effective methods for early diagnosis, monitoring metastasis, and prognosis are currently unavailable for gastric cancer. In this study, we examined the association of programmed death ligand-1 (PD-L1) and apurinic/apyrimidinic endonuclease 1 (APE1) expression with the prognosis of gastric cancer. The expressions of PD-L1 and APE1 were detected by immunohistochemistry in 107 cases of human gastric carcinoma. The correlation of PD-L1 and APE1 expression with the clinicopathologic features of gastric carcinoma was analyzed by SPSS version 19.0. The positive expression rates of PD-L1 and APE1 in gastric cancer tissues were 50.5% (54/107) and 86.9% (93/107), respectively. PD-L1 and APE1 positive expressions were significantly associated with depth of invasion, lymph node metastasis, pathological type, overall survival, and higher T stage. Furthermore, the expression of PD-L1 in highly differentiated gastric cancers was higher than that in poorly differentiated cancers (P=0.008). Moreover, the expression of APE1 and PD-L1 in gastric cancers was positively correlated (r=0.336, P<0.01). Multivariate analysis showed that the depth of invasion was a significant prognostic factor (risk ratio 19.91; P=0.000), but there was no significant relationship with PD-L1, APE1, prognosis, and other characteristics. The deregulation of PD-L1 and APE1 might contribute to the development and the poor prognosis of gastric cancer. Our findings suggest that high expression of PD-L1 and APE1 is a risk factor of gastric cancer and a new biomarker to predict the prognosis of gastric cancer. Furthermore, our findings suggest that targeting the PD-L1 and APE1 signaling pathways may be a new strategy for cancer immune therapy and targeted therapy for gastric cancer, especially in patients with deep invasion and lymph node metastasis.