■STK11(STK11Mut)基因突变可能会对非小细胞肺癌(NSCLC)患者的生存率产生负面影响,然而,其与免疫相关基因的关系尚不清楚。这项研究旨在揭示过度表达和突变的STK11是否影响NSCLC的生存,并探索免疫相关基因(IRGs)是否参与STK11突变。
■188名具有完整福尔马林固定石蜡包埋(FFPE)组织的NSCLC患者可用于检测STK11蛋白表达。免疫组织化学检测STK11蛋白后,患者分为STK11高表达组(STK11High)和STK11低表达组(STK11Low),然后采用Kaplan-Meier生存分析和COX比例风险模型比较两组患者的总生存期(OS)和无进展生存期(PFS)。此外,来自TCGA数据库的突变数据用于对NSCLC群体进行分类,即STK11突变(STK11Mut)和野生型(STK11Wt)亚组。比较了STK11Mut和STK11Wt的OS差异。最后,生物信息学分析用于比较STK11Mut和STK11Wt种群之间IRGs表达的差异。
■现实生活队列的中位随访时间为51.0个月(范围3.0-120.0个月)。在后续行动结束时,64.36%(121/188)的患者出现复发或转移。64.89%(122/188)的患者最终死于癌症相关的死亡。STK11的高表达是NSCLC患者的重要保护因素。两者在PFS方面[HR=0.42,95%CI=(0.29-0.61),P<0.001和OS[HR=0.36,95%CI=(0.25,0.53),P<0.001],这与TCGA队列中的发现一致[HR=0.76,95CI=(0.65,0.88),P<0.001HR=0.76,95CI=(0.65,0.88),P<0.001]。在TCGA队列中,就OS而言,STK11突变是肺鳞癌(LUSC)和肺腺癌(LUAD)组织学中NSCLC的重要危险因素[HR=6.81,95CI=(2.16,21.53),P<0.001;HR=1.50,95CI=(1.00,2.26),P=0.051,分别]。此外,7个IRG,即CALCA,BMP6,S100P,THPO,CGA,PCSK1和MUC5AC,在LUSC和LUAD组织学中发现STK11突变的NSCLC中显著过表达。
■蛋白水平的STK11低表达和STK11突变的存在与NSCLC的不良预后相关,和突变的STK11可能会改变IRGs的表达谱。
UNASSIGNED: Mutations in STK11 (STK11Mut) 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.
UNASSIGNED: 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 (STK11High) and low STK11 expression group (STK11Low), 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 (STK11Mut) and wild-type (STK11Wt) subgroups. The difference in OS between STK11Mut and STK11Wt was compared. Finally, bioinformatics analysis was used to compare the differences in IRGs expression between STK11Mut and STK11Wt populations.
UNASSIGNED: 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), P<0.001] and OS [HR=0.36, 95% CI= (0.25, 0.53), P<0.001], which was consistent with the finding in TCGA cohorts [HR=0.76, 95%CI= (0.65, 0.88), P<0.001 HR=0.76, 95%CI= (0.65, 0.88), P<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), P<0.001; HR=1.50, 95%CI= (1.00, 2.26), P=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.
UNASSIGNED: 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.