Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, No. 277 Yanta West Road, Xi'an, 710061, Shaanxi, China.
Department of Endocrinology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710043, Shaanxi, China.
Sci Rep. 2023 Feb 20;13(1):2923. doi: 10.1038/s41598-022-23979-z.
The NLR family CARD domain containing 3 (NLRC3) gene has been reported to have a crucial effect on immunity, inflammation, and tumorigenesis. However, the clinical relevance of NLRC3 in lung adenocarcinoma (LUAD) remains unclear. This study analyzed both RNA sequencing data and corresponding clinical outcomes obtained from public databases to identify (i) NLRC3 as a tumor suppressor in LUAD and (ii) its predictive value for the likelihood of patient responsiveness to immunotherapy. The results showed that NLRC3 expression was reduced in LUAD and was lower in advanced-stage tumors. Additionally, reduced NLRC3 expression was correlated with worse patient prognosis. The protein level of NLRC3 was also observed to have prognostic significance. Moreover, downregulation of NLRC3 was found to suppress the chemotaxis and infiltration of antitumor lymphocyte subpopulations as well as natural killer cells. Mechanistic analysis indicated that NLRC3 may be involved in immune infiltration by regulating chemokines and their receptors in LUAD. Furthermore, NLRC3 functions as a molecular switch in macrophages, whereby it mediates the polarization of M1 macrophages. Patients with high NLRC3 expression were also found to exhibit a more promising response to immunotherapy. In conclusion, NLRC3 could serve as a potential prognostic biomarker for LUAD, help predict the immunotherapeutic response of patients, and guide personalized strategies for the treatment of LUAD.
NLR 家族 CARD 结构域包含 3（NLRC3）基因已被报道对免疫、炎症和肿瘤发生具有重要影响。然而，NLRC3 在肺腺癌（LUAD）中的临床相关性尚不清楚。本研究通过分析公共数据库中的 RNA 测序数据和相应的临床结果，确定了（i）NLRC3 是 LUAD 的肿瘤抑制因子，以及（ii）其对患者对免疫治疗反应可能性的预测价值。结果表明，NLRC3 在 LUAD 中的表达降低，且在晚期肿瘤中表达水平更低。此外，NLRC3 表达降低与患者预后不良相关。NLRC3 的蛋白水平也具有预后意义。此外，下调 NLRC3 被发现抑制抗肿瘤淋巴细胞亚群和自然杀伤细胞的趋化和浸润。机制分析表明，NLRC3 可能通过调节 LUAD 中的趋化因子及其受体参与免疫浸润。此外，NLRC3 在巨噬细胞中作为分子开关发挥作用，介导 M1 巨噬细胞的极化。还发现高 NLRC3 表达的患者对免疫治疗的反应更有希望。总之，NLRC3 可作为 LUAD 的潜在预后生物标志物，有助于预测患者的免疫治疗反应，并指导 LUAD 的个体化治疗策略。
