Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
Department of Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
Pathol Oncol Res. 2021 Apr 16;27:607385. doi: 10.3389/pore.2021.607385. eCollection 2021.
Nucleotide-binding and leucine-rich repeat protein (NLRP) genes are involved in inflammasome formation that plays a role in inflammation/host defense and cell death. Both cell death and inflammation are crucial for cancer development, but the roles of NLRPs in cancer are partially known. In this study, we analyzed mononucleotide repeats in coding sequences of and and found 1, 1, 1 and 8 frameshift mutation (s) in gastric (GC) and colonic cancers (CRC), respectively. Five of the 32 high microsatellite instability (MSI-H) GCs (15.5%) and 6 of 113 MSI-H CRCs (5.5%) exhibited the frameshift mutations. There was no frameshift mutations in microsatellite stable (MSS) GCs and CRCs. We also discovered that 2 of 16 CRCs (12.5%) harbored intratumoral heterogeneity (ITH) of the frameshift mutations in one or more areas. In both GC and CRC with MSI-H, NLRP9 expression in -mutated cases was significantly lower than that in -non-mutated cases. Our data indicate that is altered at multiple levels (frameshift mutation, mutational ITH and loss of expression), which together could contribute to pathogenesis of MSI-H GC and CRC.
核苷酸结合和富含亮氨酸重复蛋白 (NLRP) 基因参与炎症小体的形成，在炎症/宿主防御和细胞死亡中发挥作用。细胞死亡和炎症对于癌症的发展都至关重要，但 NLRP 在癌症中的作用部分已知。在这项研究中，我们分析了编码序列中的单核苷酸重复，发现胃（GC）和结肠（CRC）癌症分别存在 1、1、1 和 8 个移码突变（s）。32 个高微卫星不稳定性（MSI-H）GC 中有 5 个（15.5%）和 113 个 MSI-H CRC 中有 6 个（5.5%）存在移码突变。微卫星稳定（MSS）GC 和 CRC 中均未发现 移码突变。我们还发现，在 16 个 CRC 中有 2 个（12.5%）在一个或多个区域存在 移码突变的肿瘤内异质性（ITH）。在 MSI-H 的 GC 和 CRC 中，发生 突变的病例中 NLRP9 的表达明显低于未发生 突变的病例。我们的数据表明，在多个层面上发生了改变（移码突变、突变 ITH 和表达缺失），这些改变可能共同导致 MSI-H GC 和 CRC 的发病机制。
