Liu Yan, Liu Pengpeng, Zhang Rui, Seki Nobuhiko, Forest Fabien, Brueckl Wolfgang M, Zhao Cuicui, Zhang Chuangui, Yu Jinpu
VIP Ward, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center of Caner, Key Laboratory of Cancer Prevention and Therapy, Key Laboratory of Cancer Immunology and Biotherapy, Tianjin, China.
Tianjin's Clinical Research Center for Cancer, Tianjin, China.
J Thorac Dis. 2024 Sep 30;16(9):6204-6215. doi: 10.21037/jtd-24-1122. Epub 2024 Sep 18.
Current knowledge about the prognostic role of interleukin-33 (IL-33) in lung squamous cell carcinoma (LUSC) remains limited, particularly in stage II-III patients. This study aimed to verify the correlation between IL-33 expression and poor prognosis in stage II-III LUSC patients at both gene and protein levels and to investigate the potential role of IL-33 blockade in combination with immune checkpoint inhibitors (ICIs) in perioperative immunotherapy.
A retrospective analysis was conducted of 103 patients with stage II-III LUSC who underwent surgical resection at Tianjin Medical University Cancer Institute & Hospital from November 1, 2004, to November 30, 2006. Of these, 83 patients were included based on complete follow-up data, and were divided into a gene expression group (38 patients) and a protein expression group (45 patients). IL-33 expression was analyzed using real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC). The correlation between IL-33 expression and overall survival (OS) was assessed using Kaplan-Meier survival analysis. Additionally, IHC results from 20 patients were used to explore the correlation between IL-33, programmed death ligand 1 (PD-L1), and Ki-67 expression levels. The total follow-up time exceeded 60 months, and the study endpoint was OS.
Patients with high IL-33 expression had significantly shorter OS compared to those with low IL-33 expression, both at the gene (P=0.006) and protein expression (P=0.01). Logistic regression analysis confirmed IL-33 as an independent prognostic factor for poor survival in stage II-III LUSC (P=0.04, P=0.009). Additionally, a significant positive correlation was observed between the protein expression of IL-33 (P=0.03), PD-L1 (P<0.001), and Ki-67 (P=0.01), indicating that high expression of these markers is associated with worse prognosis.
High IL-33 expression in cancer tissues is associated with poor prognosis in stage II-III LUSC. IL-33 blockade combined with ICIs may provide new treatment regimens and ideas for perioperative immunotherapy in stage II-III LUSC patients.
目前关于白细胞介素-33（IL-33）在肺鳞状细胞癌（LUSC）中的预后作用的知识仍然有限，尤其是在II-III期患者中。本研究旨在验证II-III期LUSC患者在基因和蛋白水平上IL-33表达与不良预后之间的相关性，并研究IL-33阻断联合免疫检查点抑制剂（ICI）在围手术期免疫治疗中的潜在作用。
对2004年11月1日至2006年11月30日在天津医科大学肿瘤医院接受手术切除的103例II-III期LUSC患者进行回顾性分析。其中，83例患者基于完整的随访数据被纳入研究，并分为基因表达组（38例患者）和蛋白表达组（45例患者）。使用实时定量聚合酶链反应（RT-qPCR）和免疫组织化学（IHC）分析IL-33表达。使用Kaplan-Meier生存分析评估IL-33表达与总生存期（OS）之间的相关性。此外，20例患者的IHC结果用于探索IL-33、程序性死亡配体1（PD-L1）和Ki-67表达水平之间的相关性。总随访时间超过60个月，研究终点为OS。
与低IL-33表达的患者相比，高IL-33表达的患者在基因水平（P=0.006）和蛋白表达水平（P=0.01）上的OS均显著缩短。逻辑回归分析证实IL-33是II-III期LUSC患者生存不良的独立预后因素（P=0.04，P=0.009）。此外，观察到IL-33（P=0.03）、PD-L1（P<0.001）和Ki-67（P=0.01）的蛋白表达之间存在显著正相关，表明这些标志物的高表达与更差的预后相关。
癌组织中高IL-33表达与II-III期LUSC患者的不良预后相关。IL-33阻断联合ICI可能为II-III期LUSC患者的围手术期免疫治疗提供新的治疗方案和思路。
