Hippo Pathway Core Genes Based Prognostic Signature and Immune Infiltration Patterns in Lung Squamous Cell Carcinoma.
Hippo Pathway Core Genes Based Prognostic Signature and Immune Infiltration Patterns in Lung Squamous Cell Carcinoma.
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基于 Hippo 通路核心基因的肺鳞状细胞癌的预后特征和免疫浸润模式
DOI：
10.3389/fonc.2021.680918
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发表时间：
2021
影响因子：
4.7
通讯作者：
Chen C
中科院分区：
文献类型：
--
作者：
Gu C;Chen J;Dang X;Chen C;Huang Z;Shen W;Shi X;Dai C;Chen C
背景我们研究了Hippo通路核心基因在肺鳞癌中的免疫浸润模式及其对预后的影响，以期为LUSC肿瘤发生机制的研究提供线索，并为开发新的治疗方法提供帮助。方法从TCGA数据库中提取LUSC患者的突变数据、转录组数据及相应的临床医学信息。对差异表达基因（DEG）和基因本体论（GO）、京都基因和基因组百科全书（KEGG）分析进行了探索。对hippo核心基因和预后模型进行生存分析。采用CIBERSORT算法估计免疫浸润，并进一步研究免疫检查点相关基因。结果共纳入551例LUSC标本，其中肿瘤标本502例，邻近正常标本49例。最终鉴定出1910个表达上调的DEG和2253个表达下调的DEG。前五位突变的hippo通路核心基因分别是LATS 1（4%）、WWC 1（2%）、TAOK 1（2%）、TAOK 3（2%）和TAOK 2（2%）。LATS 2突变与共突变NF 2（P <0.05）和TAOK 1（P <0.05）高度相关。在生存分析中，我们发现只有WWC 1（对数秩p = 0.046，HR = 1.32，95%CI = 1-1.73）和LATS 2（对数秩p = 0.013，HR = 1.41，95%CI = 1.08-1.86）具有显著的预后作用。根据分型结果分为三个亚组，T细胞γ δ（p = 5.78 e-6）、B细胞记忆（p = 4.61 e-4）和T细胞CD 4+静息记忆（p = 2.65 e-5）在三组间有显著性差异。SIGLEC 15（P <0.01）和CD 274（P <0.05）在三个亚组间也有统计学差异。结论WWC 1和LATS 2在LUSC患者中的预后作用得到证实。免疫检查点相关基因SIGLEC 15和CD 274在3个亚组间差异有统计学意义，这可能为LUSC的分子机制提供新的认识，并可能有助于精确选择具有潜在免疫治疗益处的特定LUSC患者。
Background 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. Methods The 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. Results Overall, 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. Conclusions Our 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.
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