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血清抗烯醇化酶1和抗鳞状上皮细胞核抗原1抗体生物标志物在预测胃癌预后中的应用。

Application of serum anti-ENO1 and anti-SSNA1 antibody biomarkers in predicting the prognosis of gastric cancer.

作者信息

Yajima Satoshi, Ito Masaaki, Suzuki Takashi, Oshima Yoko, Sumazaki Makoto, Shiratori Fumiaki, Takizawa Hirotaka, Li Shu-Yang, Zhang Bo-Shi, Yoshida Yoichi, Matsutani Tomoo, Hiwasa Takaki, Shimada Hideaki

机构信息

Department of Gastroenterological Surgery, Toho University School of Medicine, Tokyo 143-8541, Japan.

Department of Clinical Oncology, Toho University Graduate School of Medicine, Tokyo 143-8541, Japan.

出版信息

Oncol Lett. 2025 May 22;30(1):360. doi: 10.3892/ol.2025.15106. eCollection 2025 Jul.

Abstract

Given the high malignancy of advanced gastric cancer, the identification of biomarkers for the diagnosis and prognosis prediction of advanced gastric cancer is of importance. The present study conducted the serological identification of antigens by recombinant cDNA expression cloning and determined enolase 1 (ENO1) and Sjögren syndrome nuclear autoantigen 1 (SSNA1) as tumor antigens recognized by serum immunoglobulin G (IgG) antibodies in patients with gastric cancer. The clinicopathological significance of preoperative autoantibodies were assessed, namely serum anti-ENO1 antibodies (s-ENO1-Abs) and serum anti-SSNA1 antibodies (s-SSNA-Abs), in the sera of 166 patients with gastric cancer who underwent radical surgery and 96 healthy donors. The s-ENO1-Ab and s-SSNA-Ab titer levels were significantly increased in patients with gastric cancer compared with that in healthy donors (P<0.01). Areas under the receiver operating characteristic curves of s-ENO1-Ab and s-SSNA1-Ab were 0.656 and 0.607, respectively. None of the clinicopathological factors, such as sex, age, histological type, tumor size, tumor depth, nodal status, cytology, peritoneal dissemination and stage demonstrated association with the s-ENO1-Ab or s-SSNA1-Ab titer levels. High s-ENO1-Ab and s-SSNA1-Ab titer levels were associated with improved overall survival, but the differences were not statistically significant. According to the Human Protein Atlas dataset, high mRNA expression levels of ENO1 and SSNA1 showed a trend towards shorter overall survival, while low expression levels showed a trend towards longer overall survival (ENO1: P=0.07, SSNA1: P<0.05). Combination analysis indicated that the s-ENO1-Ab-positive (+)/carcinoembryonic antigen (CEA)-negative (-) group demonstrated a significantly improved prognosis compared with that of the s-ENO1-Ab(-)/CEA(+) group (P<0.01), while a comparison of the s-SSNA1-Ab(+)/CEA(-) group with the s-SSNA1-Ab(-)/CEA(+) group also demonstrated a significant improvement in prognosis (P<0.01). Thus, s-ENO1-Abs and s-SSNA-Abs may be useful biomarkers for predicting gastric cancer prognosis, providing future research directions for novel approaches to target and treat gastric cancer.

摘要

鉴于晚期胃癌的高恶性程度,鉴定用于晚期胃癌诊断和预后预测的生物标志物具有重要意义。本研究通过重组cDNA表达克隆进行了抗原的血清学鉴定,并确定烯醇化酶1(ENO1)和干燥综合征核自身抗原1(SSNA1)为胃癌患者血清免疫球蛋白G(IgG)抗体识别的肿瘤抗原。评估了166例行根治性手术的胃癌患者和96名健康供者血清中术前自身抗体的临床病理意义,即血清抗ENO1抗体(s-ENO1-Abs)和血清抗SSNA1抗体(s-SSNA-Abs)。与健康供者相比,胃癌患者的s-ENO1-Ab和s-SSNA-Ab滴度水平显著升高(P<0.01)。s-ENO1-Ab和s-SSNA1-Ab的受试者工作特征曲线下面积分别为0.656和0.607。性别、年龄、组织学类型、肿瘤大小、肿瘤深度、淋巴结状态、细胞学、腹膜播散和分期等临床病理因素均与s-ENO1-Ab或s-SSNA1-Ab滴度水平无关。高s-ENO1-Ab和s-SSNA1-Ab滴度水平与总体生存率提高相关,但差异无统计学意义。根据人类蛋白质图谱数据集,ENO1和SSNA1的高mRNA表达水平显示总体生存时间有缩短趋势,而低表达水平则显示总体生存时间有延长趋势(ENO1:P=0.07,SSNA1:P<0.05)。联合分析表明,s-ENO1-Ab阳性(+)/癌胚抗原(CEA)阴性(-)组的预后明显优于s-ENO1-Ab(-)/CEA(+)组(P<0.01),而s-SSNA1-Ab(+)/CEA(-)组与s-SSNA1-Ab(-)/CEA(+)组相比,预后也有显著改善(P<0.01)。因此,s-ENO1-Abs和s-SSNA-Abs可能是预测胃癌预后的有用生物标志物,为靶向治疗胃癌的新方法提供了未来的研究方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0aff/12134978/0c487bfb8fcc/ol-30-01-15106-g00.jpg

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