术前血清CRLF1、PD-1水平与胃癌临床分期和术后复发的关系

Associations of preoperative serum CRLF1 and PD-1 levels with clinical stages and postoperative recurrence in gastric cancer

摘要:

目的 探讨胃癌患者术前血清细胞因子受体样因子1（CRLF1）、程序性死亡受体1（PD-1）水平与临床分期和术后复发的关系。方法 选取2021年1月—2023年12月邯郸市第一医院收治的胃癌患者98例。根据临床分期分为Ⅰ、Ⅱ期组（45例）和Ⅲ、Ⅳ期组（53例）；根据术后随访2年复发情况分为未复发组（59例）和复发组（39例）。比较各组间术前血清CRLF1、PD-1水平及临床资料，一般Logistic回归分析胃癌术后复发的影响因素，绘制受试者工作特征（ROC）曲线。结果 Ⅲ、Ⅳ期组血清CRLF1水平低于Ⅰ、Ⅱ期组，血清PD-1水平高于Ⅰ、Ⅱ期组（P 0.05）。复发组与未复发组性别构成、年龄、体质量指数、肿瘤部位构成、肿瘤最大直径、吸烟史、饮酒史、病理类型构成和术后辅助化疗率比较，差异均无统计学意义（P 0.05）。复发组分化程度为低分化占比、淋巴结转移率、远处转移率和TNM分期为Ⅲ、Ⅳ期占比均高于未复发组（P 0.05）；复发组血清CRLF1水平低于未复发组，血清PD-1水平高于未复发组（P 0.05）。多因素一般Logistic回归分析结果：血清PD-1水平高［O^R=1.010（95% CI：1.004，1.016）］和TNM为Ⅲ、Ⅳ期［O^R=28.258（95% CI：5.427，147.133）］均为胃癌术后复发的危险因素（P 0.05），血清CRLF1水平高［O^R=0.016（95% CI：0.002，0.114）］为胃癌术后复发的保护因素（P 0.05）。ROC曲线分析显示：CRLF1、PD-1、TNM分期联合预测胃癌复发的曲线下面积为0.914（95% CI：0.858，0.970），敏感性为89.7%（95% CI：0.758，0.971），特异性为88.1%（95% CI：0.771，0.951）。结论 胃癌患者术前血清CRLF1水平降低、PD-1水平升高，与更晚的临床分期及更高的术后复发风险有关，CRLF1、PD-1检测联合TNM分期对胃癌术后复发的预测能力较好。

Abstract:

Objective To evaluate the associations of preoperative serum levels of cytokine receptor-like factor 1 (CRLF1) and programmed death-1 (PD-1) with clinical stages and postoperative recurrence in patients with gastric cancer.Methods A cohort of 98 gastric cancer patients treated at our hospital from January 2021 to December 2023 was included. Patients were stratified into the stage Ⅰ-Ⅱ group (n = 45) and the stage Ⅲ-Ⅳ group (n = 53) on the basis of clinical stage. Furthermore, based on a 2-year follow-up for recurrence, they were classified as having no recurrence (recurrence group, n = 59) or confirmed recurrence (non-recurrence group, n = 39). Preoperative serum CRLF1 and PD-1 levels, and clinical data were compared among the groups. Logistic regression analysis was used to determine the influencing factors for postoperative recurrence in gastric cancer, and receiver operating characteristic (ROC) curves were plotted.Results Comparison of serum CRLF1 and PD-1 levels between the stage Ⅲ-Ⅳ group and the stage Ⅰ-Ⅱ group showed statistically significant differences (P 0.05), where the stage Ⅲ-Ⅳ group had lower serum CRLF1 levels and higher serum PD-1 levels than the stage Ⅰ-Ⅱ group. No statistically significant differences were observed between the recurrence group and the non-recurrence group in terms of sex distribution, age, body mass index (BMI), tumor location composition, maximum tumor diameter, smoking history, alcohol consumption history, pathological type composition, or the rate of postoperative adjuvant chemotherapy (P 0.05). Statistically significant differences were found between the recurrence group and the non-recurrence group in differentiation grade composition, lymph node metastasis rate, distant metastasis rate, and TNM stage composition (P 0.05), where the recurrence group had higher proportions of poorly-differentiated tumors, lymph node metastasis, distant metastasis, and TNM stage Ⅲ-Ⅳ tumors compared with the non-recurrence group. Comparison of serum CRLF1 and PD-1 levels between the recurrence group and the non-recurrence group showed statistically significant differences (P 0.05), where the recurrence group had lower serum CRLF1 levels and higher serum PD-1 levels than the non-recurrence group. High serum PD-1 levels [OR = 1.010 (95% CI: 1.004, 1.016)] and TNM stage Ⅲ-Ⅳ tumors [OR = 28.258 (95% CI: 5.427, 147.133)] were risk factors for postoperative recurrence of gastric cancer (P 0.05), while high serum CRLF1 levels [OR = 0.016 (95% CI: 0.002, 0.114)] were a protective factor against postoperative recurrence (P 0.05). The area under the curve (AUC) of CRLF1 for predicting postoperative recurrence in gastric cancer was 0.768 (95% CI: 0.674, 0.862), with a sensitivity of 89.7% (95% CI: 0.758, 0.971) and a specificity of 55.9% (95% CI: 0.424, 0.688). The AUC of CRLF1 combined with PD-1 was 0.825 (95% CI: 0.742, 0.907), with a sensitivity of 97.4% (95% CI: 0.865, 0.999) and a specificity of 61.0% (95% CI: 0.474, 0.735). The AUC of the combination of CRLF1, PD-1, and TNM stages was 0.914 (95% CI: 0.858, 0.970), with a sensitivity of 89.7% (95% CI: 0.758, 0.971) and a specificity of 88.1% (95% CI: 0.771, 0.951).Conclusion Decreased preoperative serum CRLF1 levels and increased PD-1 levels in gastric cancer patients are associated with more advanced clinical stages and a higher risk of postoperative recurrence. The combination of CRLF1 and PD-1 detection with TNM staging has high clinical value for predicting postoperative recurrence in gastric cancer.