Arai Junya, Niikura Ryota, Hayakawa Yoku, Suzuki Nobumi, Hirata Yoshihiro, Ushiku Tetsuo, Fujishiro Mitsuhiro
Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
Department of Gastroenterological Endoscopy, Tokyo Medical University, Tokyo 160-0023, Japan.
Biomedicines. 2022 Apr 12;10(4):884. doi: 10.3390/biomedicines10040884.
Most gastric cancers develop in patients with chronic gastritis. Chronic gastritis can be classified into two major subtypes: Helicobacter pylori (H. pylori)-induced gastritis and autoimmune gastritis (AIG). Whereas H. pylori-related gastric cancers are more common and have been extensively investigated, the clinicopathological features of gastric cancer with autoimmune gastritis are unclear. Patients diagnosed with gastric cancer and hospitalized in the University Tokyo Hospital from 1998 to 2017 were enrolled. Diagnosis of autoimmune gastritis was based on positivity for serum anti-parietal cell antibody (APCA). We evaluated mucin expression and immune cell infiltration by immunohistochemical staining for MUC5AC, MUC6, PD-L1, CD3, CD11, Foxp3, and PD1. We also examined the presence of bacterial taxa that are reportedly enriched in AIG. Survival analyses of recurrence and 5-year mortality were also performed. In total, 261 patients (76 APCA-positive and 185 APCA-negative) were analyzed. Immunohistochemical staining in the matched cohort showed that AIG-related gastric cancer had higher MUC5AC expression (p = 0.0007) and MUC6 expression (p = 0.0007). Greater infiltration of CD3-positive (p = 0.001), Foxp3-positive (p < 0.001), and PD1-positive cells (p = 0.001); lesser infiltration of CD11b-positive (p = 0.005) cells; and a higher prevalence of Bacillus cereus (p = 0.006) were found in AIG-related gastric cancer patients. The cumulative incidences of gastric cancer recurrence were 2.99% at 2 years, 15.68% at 6 years, and 18.81% at 10 years in APCA-positive patients; they were 12.79% at 2 years, 21.35% at 6 years, and 31.85% at 10 years in APCA-negative patients. The cumulative incidences of mortality were 0% at 3 years and 0% at 5 years in APCA-positive patients; they were 1.52% at 3 years and 2.56% at 5 years in APCA-negative patients. We identified molecular differences between AIG and non-AIG gastric cancer. Differences in T-cell populations and the gastric microbiota may contribute to the pathogenesis of gastric cancers and potentially affect the response to immunotherapy.
大多数胃癌发生于慢性胃炎患者。慢性胃炎可分为两大主要亚型：幽门螺杆菌（H. pylori）感染性胃炎和自身免疫性胃炎（AIG）。虽然幽门螺杆菌相关胃癌更为常见且已得到广泛研究，但自身免疫性胃炎相关胃癌的临床病理特征尚不清楚。纳入1998年至2017年在东京大学医院诊断为胃癌并住院的患者。自身免疫性胃炎的诊断基于血清抗壁细胞抗体（APCA）阳性。我们通过对MUC5AC、MUC6、PD-L1、CD3、CD11、Foxp3和PD1进行免疫组织化学染色来评估黏蛋白表达和免疫细胞浸润。我们还检测了据报道在AIG中富集的细菌类群的存在情况。还进行了复发和5年死亡率的生存分析。总共分析了261例患者（76例APCA阳性和185例APCA阴性）。配对队列中的免疫组织化学染色显示，AIG相关胃癌具有更高的MUC5AC表达（p = 0.0007）和MUC6表达（p = 0.0007）。在AIG相关胃癌患者中发现CD3阳性（p = 0.001）、Foxp3阳性（p < 0.001）和PD1阳性细胞（p = 0.001）的浸润更多；CD11b阳性细胞（p = 0.005）的浸润较少；蜡样芽孢杆菌的患病率更高（p = 0.006）。APCA阳性患者胃癌复发的累积发生率在2年时为2.99%，6年时为15.68%，10年时为18.81%；APCA阴性患者在2年时为12.79%，6年时为21.35%，10年时为31.85%。APCA阳性患者的死亡率累积发生率在3年时为0%，5年时为0%；APCA阴性患者在3年时为1.52%，5年时为2.56%。我们确定了AIG和非AIG胃癌之间的分子差异。T细胞群体和胃微生物群的差异可能有助于胃癌的发病机制，并可能影响免疫治疗的反应。
