Lab of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, China.
Key Laboratory of Brain Science Research of Hainan Province, Hainan Medical University, Haikou, China.
Biosci Rep. 2021 Apr 30;41(4). doi: 10.1042/BSR20210280.
NOD-like receptor pyrin domain-3 (NLRP3) inflammasome activation is a double-edged sword in tumorigenesis. Whether NLRP3 is involved in the progression and prognosis of colorectal cancer (CRC) remains elucidated and is the focus of the present study.
Immunohistochemistry (IHC) was applied on tissue microarray (TMA) to determine the expression of NLRP3 in CRC patients. All 100 patients were divided into the low NLRP3 group and the high NLRP3 group according to their NLRP3 IHC scoring. Additionally, CRC xenografts were established by injecting HCT116 or RKO cells subcutaneously into nude mice. Cell proliferation and apoptosis were determined in HCT116 cells after treatment with NLRP3 inhibitor MCC950.
NLRP3 expression was up-regulated in colon adenocarcinoma tissues compared with that in paracancerous tissues in CRC patients, HCT116 xenograft, and RKO xenograft. High NLRP3 level correlated with the advanced TNM classification of malignant tumors, the occurrence of distant metastasis, vascular invasion, and positive lymph nodes. Furthermore, Kaplan-Meier survival analysis revealed that a high NLRP3 level was associated with a low 5-year survival rate and even a low 10-year survival rate. Moreover, the multivariable Cox proportional hazards regression model implied that NLRP3 expression level was an independent risk factor for CRC prognosis. Inhibition of NLRP3 by MCC950 suppressed cell proliferation, induced cell apoptosis, and decreased mRNA levels of interleukin 1β (IL1β) and interleukin 18 (IL18) in HCT116 cells.
High level of NLRP3 predicts poor survival in CRC patients. NLRP3 is a putative prognostic biomarker and a potential therapeutic target in CRC treatments.
核苷酸结合寡聚化结构域样受体蛋白 3（NLRP3）炎性小体的激活在肿瘤发生中是一把双刃剑。NLRP3 是否参与结直肠癌（CRC）的进展和预后仍需阐明，这也是本研究的重点。
应用组织微阵列（TMA）免疫组织化学（IHC）检测 CRC 患者 NLRP3 的表达。根据 NLRP3 IHC 评分，将 100 例患者分为低 NLRP3 组和高 NLRP3 组。此外，通过将 HCT116 或 RKO 细胞皮下注射到裸鼠中建立 CRC 异种移植瘤。用 NLRP3 抑制剂 MCC950 处理 HCT116 细胞后，检测细胞增殖和凋亡。
与 CRC 患者的癌旁组织、HCT116 异种移植瘤和 RKO 异种移植瘤相比，NLRP3 在结肠腺癌组织中表达上调。高 NLRP3 水平与恶性肿瘤的晚期 TNM 分类、远处转移、血管侵犯和阳性淋巴结相关。此外，Kaplan-Meier 生存分析显示，高 NLRP3 水平与低 5 年生存率甚至低 10 年生存率相关。此外，多变量 Cox 比例风险回归模型表明，NLRP3 表达水平是 CRC 预后的独立危险因素。用 MCC950 抑制 NLRP3 可抑制 HCT116 细胞的增殖，诱导细胞凋亡，并降低白细胞介素 1β（IL1β）和白细胞介素 18（IL18）的 mRNA 水平。
高 NLRP3 水平预示 CRC 患者的生存不良。NLRP3 是 CRC 治疗中一种有前途的预后生物标志物和潜在治疗靶点。
