Department of Radiation Oncology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China.
Department of Medical Oncology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China.
Front Immunol. 2024 Apr 26;15:1387896. doi: 10.3389/fimmu.2024.1387896. eCollection 2024.
Mutations in STK11 (STK11) gene may present a negative impact on survival in Non-small Cell Lung Cancer (NSCLC) patients, however, its relationship with immune related genes remains unclear. This study is to unveil whether overexpressed- and mutated-STK11 impact survival in NSCLC and to explore whether immune related genes (IRGs) are involved in STK11 mutations.
188 NSCLC patients with intact formalin-fixed paraffin-embedded (FFPE) tissue available for detecting STK11 protein expression were included in the analysis. After immunohistochemical detection of STK11 protein, patients were divided into high STK11 expression group (STK11) and low STK11 expression group (STK11), and then Kaplan-Meier survival analysis and COX proportional hazards model were used to compare the overall survival (OS) and progression-free survival (PFS) of the two groups of patients. In addition, the mutation data from the TCGA database was used to categorize the NSCLC population, namely STK11 Mutated (STK11) and wild-type (STK11) subgroups. The difference in OS between STK11 and STK11 was compared. Finally, bioinformatics analysis was used to compare the differences in IRGs expression between STK11 and STK11 populations.
The median follow-up time was 51.0 months (range 3.0 - 120.0 months) for real-life cohort. At the end of follow-up, 64.36% (121/188) of patients experienced recurrence or metastasis. 64.89% (122/188) of patients ended up in cancer-related death. High expression of STK11 was a significant protective factor for NSCLC patients, both in terms of PFS [HR=0.42, 95% CI= (0.29-0.61), <0.001] and OS [HR=0.36, 95% CI= (0.25, 0.53), <0.001], which was consistent with the finding in TCGA cohorts [HR=0.76, 95%CI= (0.65, 0.88), <0.001 HR=0.76, 95%CI= (0.65, 0.88), <0.001]. In TCGA cohort, STK11 mutation was a significant risk factor for NSCLC in both lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) histology in terms of OS [HR=6.81, 95%CI= (2.16, 21.53), <0.001; HR=1.50, 95%CI= (1.00, 2.26), =0.051, respectively]. Furthermore, 7 IRGs, namely CALCA, BMP6, S100P, THPO, CGA, PCSK1 and MUC5AC, were found significantly overexpressed in STK11-mutated NSCLC in both LUSC and LUAD histology.
Low STK11 expression at protein level and presence of STK11 mutation were associated with poor prognosis in NSCLC, and mutated STK11 might probably alter the expression IRGs profiling.
STK11（STK11）基因突变可能对非小细胞肺癌（NSCLC）患者的生存产生负面影响，但其与免疫相关基因的关系尚不清楚。本研究旨在揭示高表达和突变的 STK11 是否影响 NSCLC 患者的生存，并探讨免疫相关基因（IRGs）是否参与 STK11 突变。
纳入了 188 名有完整福尔马林固定石蜡包埋（FFPE）组织可用于检测 STK11 蛋白表达的 NSCLC 患者进行分析。在检测 STK11 蛋白的免疫组织化学后，将患者分为 STK11 高表达组（STK11）和 STK11 低表达组（STK11），然后使用 Kaplan-Meier 生存分析和 COX 比例风险模型比较两组患者的总生存（OS）和无进展生存（PFS）。此外，还使用 TCGA 数据库中的突变数据对 NSCLC 人群进行分类，即 STK11 突变（STK11）和野生型（STK11）亚组。比较 STK11 和 STK11 之间的 OS 差异。最后，使用生物信息学分析比较 STK11 和 STK11 人群中 IRGs 表达的差异。
真实队列的中位随访时间为 51.0 个月（范围 3.0-120.0 个月）。随访结束时，64.36%（121/188）的患者出现复发或转移。64.89%（122/188）的患者死于癌症相关原因。STK11 高表达是 NSCLC 患者的显著保护因素，无论是在 PFS[HR=0.42，95%CI=（0.29-0.61），<0.001]还是 OS[HR=0.36，95%CI=（0.25，0.53），<0.001]方面，这与 TCGA 队列的结果一致[HR=0.76，95%CI=（0.65，0.88），<0.001；HR=0.76，95%CI=（0.65，0.88），<0.001]。在 TCGA 队列中，STK11 突变是 LUSC 和 LUAD 组织学中 NSCLC 的显著预后因素，在 OS 方面[HR=6.81，95%CI=（2.16，21.53），<0.001；HR=1.50，95%CI=（1.00，2.26），=0.051]。此外，在 LUSC 和 LUAD 组织学中，7 个 IRGs，即 CALCA、BMP6、S100P、THPO、CGA、PCSK1 和 MUC5AC，在 STK11 突变的 NSCLC 中表达明显上调。
STK11 蛋白水平低表达和存在 STK11 突变与 NSCLC 患者的预后不良相关，并且突变的 STK11 可能改变 IRGs 表达谱。
