Yang Shuo, Liu Xiaozhen, Mao Shiqi, Shao Chuchu, Li Xuefei, Zhao Chao, Wang Yan, Fang Qiyu, Chen Bin, Wu Fengying, Chen Xiaoxia, Ren Shengxiang, Chen Xiaohui, Yu Jia
Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
J Thorac Dis. 2025 Aug 31;17(8):5921-5935. doi: 10.21037/jtd-2025-216. Epub 2025 Aug 27.
BIRC5, also known as survivin, is the smallest but functionally most complex member of the inhibitor of apoptosis protein (IAP) family and plays an important role in tumorigenesis, recurrence, and chemoresistance, this study aimed to investigate its impact on the clinical and tumor microenvironmental features of lung adenocarcinoma (LUAD), together with its prognostic values.
Clinical and transcriptomic data of 535 LUAD samples, 59 normal lung, and 54 patients with non-small cell lung cancer (NSCLC) received immune checkpoint blockades (ICBs) were analyzed. Immune infiltration analysis was conducted to uncover the relationship between tumor microenvironmental features and BIRC5 expression level. The prognostic values of BIRC5 were also evaluated with log-rank test and Cox regression analysis.
LUAD had a significantly higher BIRC5 expression level than normal lung tissues. The elevated BIRC5 expression was markedly associated with unfavorable clinical outcomes. Transcriptomic and single-cell sequencing data analysis revealed that tumors with high BIRC5 expression was correlated with multiple pathways' enrichment. Immune infiltration analysis indicated a negative correlation between BIRC5 expression and infiltration levels of CD8+ T cells, dendritic cells (DCs), and natural killer (NK) cell in LUAD, but a positive correlation was observed between BIRC5 expression and regulatory T cells (Tregs) infiltrations. Importantly, NSCLC patients received ICB with high BIRC5 expression had dramatically shorter progression-free survival (PFS; 1.2 4.5 months; P=0.01) and overall survival (OS; 3.1 12.7 months; P=0.005) than those with low BIRC5 expression.
These findings suggested that high BIRC5 expression was associated with DNA damage/repair, cell invasion and proliferation related pathways enrichment and increased Tregs infiltration, which would result in inferior outcomes in NSCLC received ICB.
BIRC5，也称为生存素，是凋亡抑制蛋白（IAP）家族中最小但功能最复杂的成员，在肿瘤发生、复发和化疗耐药中起重要作用。本研究旨在探讨其对肺腺癌（LUAD）临床和肿瘤微环境特征的影响及其预后价值。
分析了535例LUAD样本、59例正常肺组织样本以及54例接受免疫检查点阻断（ICB）的非小细胞肺癌（NSCLC）患者的临床和转录组数据。进行免疫浸润分析以揭示肿瘤微环境特征与BIRC5表达水平之间的关系。还通过对数秩检验和Cox回归分析评估了BIRC5的预后价值。
LUAD的BIRC5表达水平显著高于正常肺组织。BIRC5表达升高与不良临床结局显著相关。转录组和单细胞测序数据分析显示，BIRC5高表达的肿瘤与多种通路的富集相关。免疫浸润分析表明，LUAD中BIRC5表达与CD8 + T细胞、树突状细胞（DC）和自然杀伤（NK）细胞的浸润水平呈负相关，但BIRC5表达与调节性T细胞（Treg）浸润呈正相关。重要的是，接受ICB的高BIRC5表达的NSCLC患者的无进展生存期（PFS；1.2 4.5个月；P = 0.01）和总生存期（OS；3.1 12.7个月；P = 0.005）明显短于低BIRC5表达的患者。
这些发现表明，高BIRC5表达与DNA损伤/修复、细胞侵袭和增殖相关通路的富集以及Treg浸润增加有关，这将导致接受ICB的NSCLC患者预后较差。
