Chen Zhifu, Wang Yan, Chen Jun, Xu Zijun, Zhang Tingjuan, Sun Lu, Zhu Lihua, Xu Liben, Wu Chaoyang, Qiu Zhiyuan, Wang Dianjun, Wu Ting
Department of Radiation Oncology, The People's Hospital Affiliated to Jiangsu University, Zhenjiang, Jiangsu, China.
Central Laboratory, The People's Hospital Affiliated to Jiangsu University, Zhenjiang, Jiangsu, China.
Front Oncol. 2025 Jan 17;14:1426592. doi: 10.3389/fonc.2024.1426592. eCollection 2024.
Esophageal 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.
60 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.
Among 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 ( < 0.05). The differentially expressed genes GPR56, MMP9, and NFIX selected from the GSE43519 dataset were significantly downregulated after NCRT ( < 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 ( < 0.05). In addition, patients with inadequate MPR and high GPR56 expression had shorter OS ( < 0.05).
The 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.
食管癌是一种具有高度侵袭性的恶性肿瘤。新辅助放化疗不仅能提高完全切除率，还能改善中位生存期。然而，临床实践中迫切需要一种敏感的生物标志物。
选取江苏大学附属人民医院60例接受新辅助放化疗（NCRT）的食管鳞状细胞癌（ESCC）患者。根据美国病理学家学会（CAP）的肿瘤退缩分级（TRG）标准对患者进行分组。分析TRG组、临床病理特征与预后之间的相关性。利用公共数据库（GSE43519）对ESCC患者NCRT前后进行差异基因表达分析。将基质金属蛋白酶9（MMP9）、核因子I/X（NFIX）和G蛋白偶联受体56（GPR56）鉴定为候选基因，并通过免疫组化分析评估它们的表达及其与预后的相关性。
60例接受NCRT后手术的ESCC患者中，病理完全缓解（pCR）率为35.0%（21/60），主要病理缓解（MPR）率为60.0%（36/60）。肿瘤低分化以及神经或血管侵犯与肿瘤退缩分级不足相关，是影响TRG的独立因素。ESCC患者分为有效组（TRG 0 + 1）和无效组（TRG 2 + 3）。TRG越高，总生存期（OS）越短。我们的研究还通过单因素和多因素Cox回归分析确定TRG为独立预后因素（P < 0.05）。从GSE43519数据集中筛选出的差异表达基因GPR56、MMP9和NFIX在NCRT后显著下调（P < 0.001）。免疫组化显示，GPR56在ESCC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有显著差异。GPR56表达与公共数据集一致，GPR56高表达患者的OS明显较短（P < 0.05）。此外，MPR不足且GPR56高表达的患者OS较短（P < 0.05）。
研究结果表明，TRG是NCRT后ESCC的独立预后因素。发现GPR56高表达与ESCC预后不良相关。GPR56的下调结合MPR分析提示具有潜在的显著预测价值。
