Shen Yang, Xu Haibo, Guan Zhihong, Lv Mengmeng, Qian Tianye, Wu Yuzhong
Department of Gynecologic Oncology, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research and The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China.
Department of Gynecology, Affiliated Cancer Hospital of Nantong University, Nantong, China.
Transl Cancer Res. 2021 Oct;10(10):4440-4453. doi: 10.21037/tcr-21-1946.
This study aimed to investigate the relationship between Rho GTPase activating protein 9 (ARHGAP9) combined with preoperative ratio of platelet distribution width to platelet count (PDW/PLT) and patients prognosis with serous ovarian cancer.
The clinical data of 80 patients with serous ovarian cancer treated in Jiangsu Cancer Hospital from May 2011 to May 2016 were analyzed retrospectively. We verified ARHGAP9 expression in The Cancer Genome Atlas (TCGA) database, then detected messenger RNA (mRNA) expression encoding ARHGAP9 in ovarian cancer tissue samples using reverse transcription quantitative polymerase chain reaction (RT-qPCR). These patients were divided into an ARHGAP9 low-expression group and an ARHGAP9 high-expression group. The optimal critical value of PDW/PLT was determined by receiver operating characteristic (ROC) curve. The patients were divided into low PDW/PLT group and high PDW/PLT group. Kaplan-Meier method and log-rank test were used for univariate survival analysis, Cox regression method was used for multivariate analysis, and then a nomogram was constructed for internal verification.
The ARHGAP9 protein was highly expressed both in TCGA serous ovarian cancer database and the serous ovarian cancer tumor tissues. There were significant differences in menstrual status, the International Federation of Gynecology and Obstetrics (FIGO) stage and grade between the ARHGAP9 low expression group and ARHGAP9 high expression group (all P<0.05). There were significant differences in FIGO stage, lymph node metastasis, and ascites between the low PDW/PLT group and high PDW/PLT group (all P<0.05). Finally, 80 patients were included, with a mortality rate of 45.0% and a survival rate of 55.0%; the median progression-free survival (PFS) was 19 months, and the median overall survival (OS) was 62.5 months. Cox multivariate analysis showed that PDW/PLT and ARHGAP9 were independent risk factors for tumor progression (P=0.026 and P=0.028, respectively). In the internal validation, the C-index of the nomogram was 0.6518 [95% confidence interval (CI): 0.5685 to 0.7352], and the prediction model had certain accuracy.
ARHGAP9 and PDW/PLT Decrease can significantly prolong OS and PFS in serous ovarian cancer patients. Therefore, ARHGAP9 can be used as a new predictive biomarker and may be related to the immune infiltration of serous ovarian cancer.
本研究旨在探讨Rho鸟苷三磷酸酶激活蛋白9(ARHGAP9)联合术前血小板分布宽度与血小板计数比值(PDW/PLT)与浆液性卵巢癌患者预后的关系。
回顾性分析2011年5月至2016年5月在江苏省肿瘤医院接受治疗的80例浆液性卵巢癌患者的临床资料。我们在癌症基因组图谱(TCGA)数据库中验证了ARHGAP9的表达,然后使用逆转录定量聚合酶链反应(RT-qPCR)检测卵巢癌组织样本中编码ARHGAP9的信使核糖核酸(mRNA)表达。这些患者被分为ARHGAP9低表达组和ARHGAP9高表达组。通过受试者操作特征(ROC)曲线确定PDW/PLT的最佳临界值。患者被分为低PDW/PLT组和高PDW/PLT组。采用Kaplan-Meier法和对数秩检验进行单因素生存分析,采用Cox回归法进行多因素分析,然后构建列线图进行内部验证。
ARHGAP9蛋白在TCGA浆液性卵巢癌数据库和浆液性卵巢癌肿瘤组织中均高表达。ARHGAP9低表达组和ARHGAP9高表达组在月经状态、国际妇产科联盟(FIGO)分期和分级方面存在显著差异(均P<0.05)。低PDW/PLT组和高PDW/PLT组在FIGO分期、淋巴结转移和腹水方面存在显著差异(均P<0.05)。最终纳入80例患者,死亡率为45.0%,生存率为55.0%;中位无进展生存期(PFS)为19个月,中位总生存期(OS)为62.5个月。Cox多因素分析显示,PDW/PLT和ARHGAP9是肿瘤进展的独立危险因素(分别为P=0.026和P=0.028)。在内部验证中,列线图的C指数为0.6518[95%置信区间(CI):0.5685至0.7352],预测模型具有一定的准确性。
ARHGAP9和PDW/PLT降低可显著延长浆液性卵巢癌患者的OS和PFS。因此,ARHGAP9可作为一种新的预测生物标志物,可能与浆液性卵巢癌的免疫浸润有关。