Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, China.
Cancer Sci. 2024 Apr;115(4):1141-1153. doi: 10.1111/cas.16080. Epub 2024 Jan 29.
The indigenous microbial milieu within tumorous tissues exerts a pivotal influence on the genesis and advancement of gastric cancer (GC). This investigation scrutinizes the functions and molecular mechanisms attributed to Prevotella intermedia in the malignant evolution of GC. Isolation of P. intermedia from paired GC tissues was undertaken. Quantification of P. intermedia abundance in 102 tissues was accomplished using quantitative real-time PCR (qRT-PCR). Assessment of the biological effects of P. intermedia on GC cells was observed using culture medium supernatant. Furthermore, the protein profile of GC cells treated with tumor-derived P. intermedia was examined through label-free protein analysis. The functionality of perilipin 3 (PLIN3) was subsequently confirmed using shRNA. Our investigation revealed that the relative abundance of P. intermedia in tumor tissues significantly surpassed that of corresponding healthy tissues. The abundance of P. intermedia exhibited correlations with tumor differentiation (p = 0.006), perineural invasion (p = 0.004), omentum majus invasion (p = 0.040), and the survival duration of GC patients (p = 0.042). The supernatant derived from tumor-associated P. intermedia bolstered the proliferation, clone formation, migration, and invasion of GC cells. After indirect co-cultivation with tumor-derived P. intermedia, dysregulation of 34 proteins, including PLIN3, was discerned in GC cells. Knockdown of PLIN3 mitigated the malignancy instigated by P. intermedia in GC cells. Our findings posit that P. intermedia from the tumor microenvironment plays a substantial role in the malignant progression of GC via the modulation of PLIN3 expression. Moreover, the relative abundance of P. intermedia might serve as a potential biomarker for the diagnosis and prognosis of GC.
肿瘤组织内的本土微生物环境对胃癌（GC）的发生和发展起着关键作用。本研究探讨了中间普氏菌在 GC 恶性演变中的作用和分子机制。从配对的 GC 组织中分离中间普氏菌。使用定量实时 PCR（qRT-PCR）定量 102 个组织中的中间普氏菌丰度。观察 GC 细胞培养物上清液中中间普氏菌对 GC 细胞的生物学效应。此外，通过无标记蛋白质分析检查用肿瘤衍生的中间普氏菌处理的 GC 细胞的蛋白质图谱。随后使用 shRNA 确认脂联素 3 (PLIN3) 的功能。我们的研究表明，肿瘤组织中中间普氏菌的相对丰度明显高于相应的健康组织。中间普氏菌的丰度与肿瘤分化（p = 0.006）、神经周围浸润（p = 0.004）、大网膜 majus 浸润（p = 0.040）和 GC 患者的生存时间（p = 0.042）相关。源自肿瘤相关中间普氏菌的上清液增强了 GC 细胞的增殖、克隆形成、迁移和侵袭。间接与肿瘤衍生的中间普氏菌共培养后，GC 细胞中发现包括 PLIN3 在内的 34 种蛋白质失调。PLIN3 的敲低减轻了 P. intermedia 在 GC 细胞中引发的恶性转化。我们的研究结果表明，肿瘤微环境中的中间普氏菌通过调节 PLIN3 的表达在 GC 的恶性进展中起着重要作用。此外，中间普氏菌的相对丰度可能成为 GC 诊断和预后的潜在生物标志物。
