Table 1_Identification of biomarkers for tumor regression grade in esophageal squamous cell carcinoma patients after neoadjuvant chemoradiotherapy.xlsx

BackgroundEsophageal cancer is a highly invasive malignancy. Neoadjuvant chemoradiotherapy not only increases the rate of complete resection but also improves the median survival. However, a sensitive biomarker is urgently needed in clinical practice.
Methods60 esophageal squamous cell carcinoma (ESCC) patients undergoing neoadjuvant chemoradiotherapy (NCRT) were enrolled at the People's Hospital Affiliated to Jiangsu University. Patients were grouped according to tumor regression grade (TRG) criteria from the College of American Pathologists (CAP). The correlation between TRG groups, clinicopathologic characteristics, and prognosis was analyzed. Differential gene expression analysis was performed on ESCC patients before and after NCRT using the public database (GSE43519). MMP9, NFIX, and GPR56 were identified as candidate genes, and their expression and correlation with prognosis were evaluated by immunohistochemical analysis.
ResultsAmong 60 ESCC patients who underwent surgery after NCRT, the pathological complete response (pCR) rate was 35.0% (21/60), and the major pathological response (MPR) rate was 60.0% (36/60). Poor tumor differentiation and neural or vascular invasion were associated with inadequate tumor regression grade and were independent factors influencing TRG. ESCC patients were divided into effective (TRG 0 + 1) and ineffective (TRG 2 + 3) groups. Higher TRG was significantly associated with shorter overall survival (OS). Our study also identified TRG as an independent prognostic factor through univariate and multivariate Cox regression analyses (P < 0.05). The differentially expressed genes GPR56, MMP9, and NFIX selected from the GSE43519 dataset were significantly downregulated after NCRT (P < 0.001). Immunohistochemistry showed that GPR56 was highly expressed in ESCC, while it was negatively expressed in paracancerous tissues. There was a significant difference in expression between cancerous and paracancerous tissues. GPR56 expression was consistent with the public dataset, and patients with high GPR56 expression had significantly shorter OS (P < 0.05). In addition, patients with inadequate MPR and high GPR56 expression had shorter OS (P < 0.05).
ConclusionsThe findings suggest that TRG serves as an independent prognostic factor for ESCC following NCRT. High GPR56 expression is found to be associated with a poor prognosis of ESCC. Downregulation of GPR56 suggests a potential significant predictive value in conjunction with MPR analysis.

背景：食管癌是一种侵袭性极强的恶性肿瘤。新辅助放化疗（Neoadjuvant Chemoradiotherapy, NCRT）不仅可提高根治性切除率，还能延长中位生存期。然而，临床实践中仍亟需灵敏的生物标志物。
方法：本研究纳入江苏大学附属人民医院的60例接受新辅助放化疗的食管鳞状细胞癌（Esophageal Squamous Cell Carcinoma, ESCC）患者，参照美国病理学家协会（College of American Pathologists, CAP）的肿瘤退缩分级（Tumor Regression Grade, TRG）标准进行分组，分析TRG分组与临床病理特征、预后的相关性。利用公共数据库GSE43519，对新辅助放化疗前后的食管鳞状细胞癌患者开展差异基因表达分析，筛选出MMP9、NFIX及GPR56作为候选基因，并通过免疫组化分析评估其表达水平及与预后的相关性。
结果：在60例接受新辅助放化疗后接受手术的食管鳞状细胞癌患者中，病理完全缓解（pathological complete response, pCR）率为35.0%（21/60），主要病理缓解（major pathological response, MPR）率为60.0%（36/60）。肿瘤低分化、伴神经或血管浸润与不良肿瘤退缩分级显著相关，且是影响TRG的独立危险因素。本研究将患者分为有效组（TRG 0+1）与无效组（TRG 2+3），更高的TRG分级与更短的总生存期（Overall Survival, OS）显著相关。通过单因素及多因素Cox回归分析证实，TRG是独立的预后影响因素（P < 0.05）。从GSE43519数据集筛选出的差异表达基因GPR56、MMP9及NFIX在新辅助放化疗后均显著下调（P < 0.001）。免疫组化结果显示，GPR56在食管鳞状细胞癌组织中高表达，而在癌旁组织中呈阴性表达，癌组织与癌旁组织的表达水平存在显著差异。GPR56的表达趋势与公共数据库结果一致，且GPR56高表达患者的总生存期显著更短（P < 0.05）。此外，MPR不佳且GPR56高表达的患者总生存期更短（P < 0.05）。
结论：本研究结果表明，TRG可作为新辅助放化疗后食管鳞状细胞癌患者的独立预后因素。GPR56高表达与食管鳞状细胞癌患者不良预后显著相关，其表达下调结合MPR分析，有望成为具有潜在临床价值的预测指标。