Identification and Validation of Immune-Related Gene Signature for Predicting Lymph Node Metastasis and Prognosis in Lung Adenocarcinoma

Frontiers in Molecular Biosciences

Zhilin Sui¹  Hongdian Zhang²  Zhentao Yu²  Ran Jia³ 

[1] Shenzhen Hospital, Chinese Academy of Medical Sciences and PeKing Union Medical College, Shenzhen, China;Department of Esophageal Cancer, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin’s Clinical Research Center for Cancer, National Clinical Research Center of Cancer, Tianjin, China;;Department of Thoracic Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital &

关键词: lung adenocarcinoma;    immune-related genes;    lymph node metastasis;    immune cell infiltration;    immune and stromal scores;    immune checkpoint genes;   

DOI  :  10.3389/fmolb.2021.679031

来源: DOAJ

【 摘 要 】

Lung cancer is a serious malignancy, and lung adenocarcinoma (LUAD) is the most common pathological subtype. Immune-related factors play an important role in lymph node metastasis. In this study, we obtained gene expression profile data for LUAD and normal tissues from the TCGA database and analyzed their immune-related genes (IRGs), and observed that 459 IRGs were differentially expressed. Further analysis of the correlation between differentially expressed IRGs and lymph node metastasis revealed 18 lymph node metastasis-associated IRGs. In addition, we analyzed the mutations status, function and pathway enrichment of these IRGs, and regulatory networks established through TF genes. We then identified eight IRGs (IKBKB, LTBR, MIF, PPARD, PPIA, PSME3, S100A6, SEMA4B) as the best predictors by LASSO Logistic analysis and used these IRGs to construct a model to predict lymph node metastasis in patients with LUAD (AUC 0.75; 95% CI: 0.7064–0.7978), and survival analysis showed that the risk score independently affected patient survival. We validated the predictive effect of risk scores on lymph node metastasis and survival using the GEO database as a validation cohort and the results showed good agreement. In addition, the risk score was highly correlated with infiltration of immune cells (mast cells activated, macrophages M2, macrophages M0 and B cells naïve), immune and stromal scores, and immune checkpoint genes (LTBR, CD40LG, EDA2R, and TNFRSF19). We identified key IRGs associated with lymph node metastasis in LUAD and constructed a reliable risk score model, which may provide valuable biomarkers for LUAD patients and further reveal the mechanism of its occurrence.

【 授权许可】

Unknown