Department of Gastroenterology and Hepatology, University Hospital of Cologne, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.
Department of General, Visceral, Cancer and Transplantation Surgery, University Hospital Cologne, University of Cologne, Cologne, Germany.
Sci Rep. 2022 Mar 4;12(1):3584. doi: 10.1038/s41598-022-07580-y.
Current recommendations suggest neoadjuvant treatment in node-positive esophageal cancer or tumors staged T3 and upwards but some T2 N0 patients might benefit from neoadjuvant therapy. It is of clinical relevance to identify this subgroup. Loss of epithelial apicobasal polarity is a key factor in the development of invasive capabilities of carcinoma. The oncofetal stem/progenitor cell marker NOPE is expressed in adult depolarized murine hepatocytes and in murine/human hepatocellular carcinoma. We analyzed NOPE expression in 363 patients with esophageal adenocarcinoma using an RNA Scope Assay on a tissue microarray and correlated results with clinical data. Median follow-up was 57.7 months with a 5-year survival rate of 26.6%. NOPE was detectable in 32 patients (8.8%). In pT1/2 stages, NOPE expression was associated with a significantly reduced median OS of 6.3 months (95% CI 1.2-19.4 months), the median OS is not reached in the NOPE-negative group (calculated mean OS 117.1 months) (P = 0.012). In advanced tumor stages, a NOPE dependent survival difference was not detected. This is the first report of NOPE expression demonstrating a prognostic value in esophageal cancer. Early stage, NOPE positive patients are at a high risk of tumor progression and may benefit from neoadjuvant treatment analogous to advanced stage cancer.
目前的建议是对淋巴结阳性的食管癌或 T3 期及以上的肿瘤进行新辅助治疗，但一些 T2N0 患者可能受益于新辅助治疗。识别这一亚组具有临床意义。上皮细胞顶端基底极性的丧失是癌细胞侵袭能力发展的一个关键因素。癌胚胎干细胞/祖细胞标志物 NOPE 在成年去极化的小鼠肝细胞和小鼠/人肝细胞癌中表达。我们使用组织微阵列上的 RNA Scope 检测分析了 363 例食管腺癌患者的 NOPE 表达，并将结果与临床数据相关联。中位随访时间为 57.7 个月，5 年生存率为 26.6%。32 例患者（8.8%）可检测到 NOPE。在 pT1/2 期，NOPE 表达与中位 OS 显著缩短相关，中位 OS 为 6.3 个月（95%CI 1.2-19.4 个月），NOPE 阴性组的中位 OS 未达到（计算的中位 OS 为 117.1 个月）（P=0.012）。在晚期肿瘤分期中，未检测到依赖于 NOPE 的生存差异。这是首次报道 NOPE 表达在食管癌中具有预后价值。早期、NOPE 阳性的患者肿瘤进展风险高，可能受益于类似于晚期癌症的新辅助治疗。
