Matsumoto Yasunori, Sasaki Takuma, Kano Masayuki, Shiraishi Tadashi, Suito Hiroshi, Murakami Kentaro, Toyozumi Takeshi, Otsuka Ryota, Kinoshita Kazuya, Iida Shinichiro, Morishita Hiroki, Nishioka Yuri, Hayano Koichi, Kurata Yoshihiro, Hayashi Hideki, Matsubara Hisahiro
Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba 2608670, Japan.
Mol Clin Oncol. 2023 Mar 20;18(5):39. doi: 10.3892/mco.2023.2635. eCollection 2023 May.
Soluble programmed death-ligand 1 (sPD-L1) levels can be used as a biomarker for gastric cancer (GC). However, comprehensive information regarding the sPD-L1 expression profiles and their association with cachexia in GC is lacking. Therefore, the present study evaluated the association between clinicopathological findings and sPD-L1 levels in patients with GC. Serum samples were collected from patients with GC during their first visit to Department of Esophageal-Gastro-Intestinal Surgery, Chiba University Hospital, Chiba, Japan (January 2012-December 2017; n=173), and sPD-L1 levels were measured using an enzyme-linked immunosorbent assay. Survival rates among 116 patients, excluding cases with preoperative chemotherapy or no radical procedures, were analyzed. sPD-L1 levels were associated with factors such as neutrophil-to-lymphocyte ratio, hemoglobin (Hb) and albumin (Alb) levels, total cholesterol and C-reactive protein (CRP) levels, and related to inflammation and nutrition in patients. Notably, the higher the number of applicable indicators related to cachexia (Hb <12 g/dl, Alb <3.2 g/dl, CRP >0.5 mg/dl and low body mass index) was, the higher the sPD-L1 value was. However, the pathological stage did not significantly differ between the groups. Clinicopathologically, there was no association with tumor depth, lymph node metastasis or vascular invasion; however, patients with the intestinal type had significantly higher sPD-L1 levels than patients with the diffuse type (P=0.032; Wilcoxon test). The overall survival did not significantly differ between the groups with low and high sPD-L1 levels; however, among patients who received radical treatment, the relapse-free survival was significantly worse in the high-sPD-L1-level group than in the low-sPD-L1-level group (P=0.025; log-rank test). Multivariate Cox regression analysis revealed that a high sPD-L1 concentration was a sign of poor prognosis, independent of pathological stage and cancer antigen CA19-9 (P=0.0029). Therefore, the present findings suggest that sPD-L1 can reflect cachexia status in patients with GC and may serve as a prognostic marker for relapse-free survival after radical GC surgery.
可溶性程序性死亡配体1（sPD-L1）水平可作为胃癌（GC）的生物标志物。然而，关于GC中sPD-L1表达谱及其与恶病质的关联的全面信息尚缺乏。因此，本研究评估了GC患者的临床病理特征与sPD-L1水平之间的关联。收集了日本千叶大学医院食管胃肠外科首次就诊的GC患者的血清样本（2012年1月至2017年12月；n = 173），并使用酶联免疫吸附测定法测量sPD-L1水平。分析了116例患者（排除术前化疗或未进行根治性手术的病例）的生存率。sPD-L1水平与中性粒细胞与淋巴细胞比值、血红蛋白（Hb）和白蛋白（Alb）水平、总胆固醇和C反应蛋白（CRP）水平等因素相关，并且与患者的炎症和营养状况有关。值得注意的是，与恶病质相关的适用指标数量（Hb <12 g/dl、Alb <3.2 g/dl、CRP >0.5 mg/dl和低体重指数）越高，sPD-L1值越高。然而，各组之间的病理分期无显著差异。在临床病理方面，与肿瘤深度、淋巴结转移或血管侵犯无关；然而，肠型患者的sPD-L1水平显著高于弥漫型患者（P = 0.032；Wilcoxon检验）。sPD-L1水平高低组之间的总生存率无显著差异；然而，在接受根治性治疗的患者中，高sPD-L1水平组的无复发生存率显著低于低sPD-L1水平组（P = 0.025；对数秩检验）。多变量Cox回归分析显示，高sPD-L1浓度是预后不良的标志，独立于病理分期和癌抗原CA19-9（P = 0.0029）。因此，本研究结果表明，sPD-L1可反映GC患者的恶病质状态，并可能作为GC根治性手术后无复发生存的预后标志物。
