[Utility of GPR68 and TIL in TPF-induced chemotherapy and prognosis evaluation in middle-advanced hypopharyngeal squamous cell carcinoma].

Objective: To evaluate the roles of G Protein-Coupled Receptor 68 (GPR68) and tumor infiltrating lymphocytes (TIL) in TPF-(paclitaxel, cisplatin and 5-fluorouracil) induced chemotherapy for middle-advanced hypopharyngeal squamous cell carcinomas. Methods: A total of 31 patients with middle-advanced hypopharyngeal squamous cell carcinoma before TPF-inducted chemotherapy were enrolled from September 2012 to November 2017 in Beijing Tongren Hospital, Capital Medical University, including 28 males and 3 females, aged 43 to 71 years old. The expression of GPR68 and tumor infiltrating CD4+and CD8+T cells before chemotherapy was detected by immunohistochemical staining, and the relationships between GPR68 expression and clinical features, chemotherapy efficacy and overall survival (OS) were analyzed using t-test. Results: After 3 cycles of chemotherapy, there were 4, 14, 10 and 3 patients respectively with complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). The positive rates of GPR68 and CD8 were 25% and 40% respectively in the effective group (CR+PR), while 50% and 15% in the ineffective group (SD+PD), with statistically significant differences between two groups (t=5.17 and 12.86,P<0.001). Linear regression analysis showed that GPR68 was negatively correlated with CD8+T cells (r=-0.64,P<0.001). There was no significant correlation between the CD4 expression and TPF efficacy (P>0.05). The mean OS was 12.5 months in patients with high-expressed GPR68 and 25.0 months in patients with low-expressed GPR68, with a statistically significant difference (P=0.005). And mean OS was 25.0 months in patients with high-expressed CD8 and 14.5 months in low-expressed CD8, with a statistically significant difference (HR=2.58, P=0.019). Cox regression analysis showed that GPR68 and CD8+T cells were significant prognostic factors (OR(95%CI)=3.27(2.46-5.97) and 1.53(0.78-1.82), all P<0.05), while CD4 had no significant effect on prognosis (P>0.05). Conclusion: GPR68 and CD8+T cells are expected to be biomarkers for evaluating the efficacy and prognosis of TPF-induced chemotherapy in patients with middle-advanced hypopharyngeal squamous cell carcinoma.目的： 检测中晚期下咽鳞状细胞癌（简称鳞癌）患者TPF（紫杉醇+顺铂+5-氟尿嘧啶）诱导化疗前G蛋白偶联受体（G protein-coupled receptor，GPR）68的表达水平和肿瘤浸润淋巴细胞（tumor infiltrating lymphocytes，TIL）的数量，评估其对化疗疗效及预后的价值。 方法： 回顾性分析2012年9月至2017年11月首都医科大学附属北京同仁医院收治并进行TPF诱导化疗的31例中晚期下咽鳞癌患者，其中男性28例，女性3例，年龄43~71岁。通过免疫组化染色的方法检测患者化疗前肿瘤中GPR68和CD4+、CD8+T细胞的阳性率，利用t检验分析其与临床特征、化疗疗效、总生存期（overall survival，OS）之间的关系。 结果： 31例患者经3个周期化疗后，4例患者达完全缓解（CR），14例部分缓解（PR），10例疾病稳定（SD），3例疾病进展（PD）。有效组（CR+PR）中GPR68及CD8阳性率分别为25%、40%；无效组（SD+PD）中GPR68及CD8阳性率分别为50%、15%，2组相比差异有统计学意义（t值分别为5.17和12.86，P值均<0.001）；线性回归分析显示GPR68与CD8+T细胞存在负相关关系（r=-0.64，P<0.001）；CD4的表达与患者TPF疗效无相关性（P>0.05）。GPR68高表达和低表达组OS分别为12.5和25.0个月，差异有统计学意义（HR=0.30，P=0.005）；CD8高浸润和低浸润组OS分别为25.0和14.5个月，差异有统计学意义（HR=2.58，P=0.019）。Cox回归分析结果显示，GPR68、CD8+T细胞是有意义的预后因素［OR（95%CI）分别为3.27（2.46~5.97）和1.53（0.78~1.82），P值均<0.05］；而CD4对预后无影响（P>0.05）。 结论： GPR68和CD8+T细胞有希望成为评估中晚期下咽鳞癌患者TPF诱导化疗疗效和预后的生物标志物。.