Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan;
Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
Cancer Genomics Proteomics. 2023 Jul-Aug;20(4):343-353. doi: 10.21873/cgp.20386.
BACKGROUND/AIM: Squamous cell carcinoma is one of the major subtypes of esophageal carcinoma, and the 5-year overall survival rate of esophageal squamous cell carcinoma patients who underwent curative treatment remains below 40%. We aimed to detect and validate the prognosticators of esophageal squamous cell carcinoma in patients who underwent radical esophagectomy.
Comprehensive analysis of transcriptome and clinical data from The Cancer Genome Atlas revealed OPLAH as one of the differentially expressed genes between esophageal squamous cell carcinoma tissues and normal esophageal mucosa. OPLAH expression changes were significantly associated with a patient prognosis. OPLAH protein levels were further evaluated by immunohisto-chemistry in esophageal squamous cell carcinoma tissues (n=177) as well as in serum samples (n=54) using ELISA.
OPLAH mRNA was significantly overexpressed in esophageal squamous cell carcinoma tissues compared to normal esophageal mucosa, and patients with high OPLAH mRNA expression have a significantly poorer prognosis, according to The Cancer Genome Atlas data. The high staining intensity of OPLAH protein in esophageal squamous cell carcinoma tissue clearly stratified patient prognosis. According to multivariable analysis, high OPLAH protein expression was an independent prognostic factor for survival after surgery. Pre-neoadjuvant chemotherapy serum OPLAH protein concentrations were significantly associated with clinical tumor depth and node positivity and, consequently, with advanced clinical stage. The serum OPLAH protein concentration was significantly decreased by neoadjuvant chemotherapy.
OPLAH protein expression in cancerous tissue and serum may have clinical utility towards stratifying prognosis of patients with esophageal squamous cell carcinoma.
背景/目的:鳞状细胞癌是食管癌的主要亚型之一,接受根治性手术治疗的食管鳞状细胞癌患者的 5 年总生存率仍低于 40%。我们旨在检测和验证接受根治性食管切除术的食管鳞状细胞癌患者的预后标志物。
综合分析癌症基因组图谱的转录组和临床数据,揭示 OPLAH 是食管鳞状细胞癌组织与正常食管黏膜之间差异表达基因之一。OPLAH 表达的变化与患者预后显著相关。进一步通过免疫组织化学法在食管鳞状细胞癌组织(n=177)和血清样本(n=54)中评估 OPLAH 蛋白水平,并用 ELISA 检测。
根据癌症基因组图谱的数据,与正常食管黏膜相比,OPLAH mRNA 在食管鳞状细胞癌组织中明显过表达,并且高 OPLAH mRNA 表达的患者预后明显较差。OPLAH 蛋白在食管鳞状细胞癌组织中的高染色强度清楚地分层了患者的预后。根据多变量分析,高 OPLAH 蛋白表达是手术治疗后生存的独立预后因素。新辅助化疗前血清 OPLAH 蛋白浓度与临床肿瘤深度和淋巴结阳性显著相关,进而与晚期临床分期相关。新辅助化疗后血清 OPLAH 蛋白浓度明显降低。
癌组织和血清中的 OPLAH 蛋白表达可能对分层食管鳞状细胞癌患者的预后具有临床应用价值。