Hippo Pathway Core Genes Based Prognostic Signature and Immune Infiltration Patterns in Lung Squamous Cell Carcinoma.

Chang Gu,Xuening Dang,Chang Chen,Weidong Shen,Chunji Chen,Jiafei Chen,Chenyang Dai,Xin Shi,Zhenyu Huang

doi:10.3389/fonc.2021.680918

Abstract

BackgroundWe investigated the prognostic effects and their patterns of immune infiltration of hippo pathway core genes in lung squamous cell carcinoma, in order to find some clues for underlying mechanisms of LUSC tumorigenesis and help developing new therapeutic methods.MethodsThe mutational data, transcriptome data and corresponding clinical medical information of LUSC patients were extracted from The Cancer Genome Atlas (TCGA) database. Differential expression genes (DEGs) and Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were explored. Survival analysis for the hippo core genes and the prognostic model were performed. Immune infiltration was estimated by CIBERSORT algorithm and some immune checkpoints-related genes were further investigated.ResultsOverall, 551 LUSC samples were included in our study, consisting of 502 LUSC tumor samples and 49 adjacent normal samples, respectively. There were 1910 up-regulated DEGs and 2253 down-regulated DEGs were finally identified. The top five mutational hippo pathway core genes were LATS1 (4%), WWC1 (2%), TAOK1 (2%), TAOK3 (2%), and TAOK2 (2%), respectively. the mutation of LATS2 was highly associated with co-mutational NF2 (P <0.05) and TAOK1 (P <0.05). In survival analyses, we found only WWC1 (log-rank p = 0.046, HR = 1.32, 95% CI = 1–1.73) and LATS2 (log-rank p = 0.013, HR = 1.41, 95%CI = 1.08–1.86) had significant prognostic roles. After getting the three subgroups according to the subtyping results, we demonstrated that T cell gamma delta (p = 5.78e-6), B cell memory (p = 4.61e-4) and T cell CD4+ memory resting (p = 2.65e-5) had significant differences among the three groups. SIGLEC15 (P <0.01) and CD274 (P <0.05) also had statistical differences among the three subgroups.ConclusionsOur study verified the prognostic roles of WWC1 and LATS2 in LUSC patients. Immune checkpoints-related genes SIGLEC15 and CD274 had statistical differences among the three subgroups, which may provide new perceptions on the molecular mechanisms in LUSC and maybe helpful for precisely selecting specific LUSC patients with potential immunotherapy benefits.

Highlights

Lung cancer remains the first lethiferous neoplasm all around the world [1,2,3,4,5,6]
We investigated the prognostic effects and their patterns of immune infiltration of hippo pathway core genes in lung squamous cell carcinoma, in order to find some clues for underlying mechanisms of LUSC tumorigenesis and help developing new therapeutic methods
551 LUSC samples were included in our study, consisting of 502 LUSC tumor samples and 49 adjacent normal samples, respectively

Summary

Introduction

Lung cancer remains the first lethiferous neoplasm all around the world [1,2,3,4,5,6]. The process of tumorigenesis, development and metastasis of lung cancer associates with dysregulation of many signaling pathways [11]. It has been proved that the dysregulation of the Hippo signaling pathway lead to tumorigenesis, development and metastasis of diverse tumors, including lung adenocarcinoma [14], breast cancer [15], hepatocellular carcinoma [16], gastric cancer [17] and so on. Wang et al [18] highlighted the significance of Hippo signaling, including 18 core genes, in LUSC through comprehensive molecular features. We investigated the prognostic effects and their patterns of immune infiltration of hippo pathway core genes in lung squamous cell carcinoma, in order to find some clues for underlying mechanisms of LUSC tumorigenesis and help developing new therapeutic methods

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Results

Conclusion