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高表达与肺腺癌患者的不良预后和免疫浸润有关。

High Expression of Is Associated with the Poor Prognosis and Immune Infiltration in Lung Adenocarcinoma Patients.

机构信息

Department of Oncology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China.

Department of Pathology, Zhongda Hospital, Southeast University, Nanjing 210009, China.

出版信息

Dis Markers. 2022 Jul 9;2022:8789515. doi: 10.1155/2022/8789515. eCollection 2022.

Abstract

BACKGROUND

Lung adenocarcinoma (LUAD) has been recognized as one of the commonest aggressive malignant tumors occurring in humans. The transforming acidic coiled-coil-containing protein 3 () seems to be a probable prognostic marker and treatment target for non-small-cell lung cancer (NSCLC). Nevertheless, there exist no reports on the association between and immunotherapy or other therapeutic interventions in LUAD.

METHODS

Premised on the data accessed from The Cancer Genome Atlas- (TCGA-) LUAD, we carried out bioinformatics analysis. The expression in LUAD was analyzed utilizing the GEPIA. A survival module was constructed to evaluate the effect of on the survival of patients with LUAD. Logistic regression was undertaken to examine the relationship between expression and clinical factors. Protein-protein interaction analysis was performed in the GeneMANIA database, and enrichment analysis and identification of predicted signaling pathways were performed using Gene Ontology and Kyoto Encyclopedia of Genes. Additionally, the Cox regression was used to assess the clinicopathologic features linked to the overall survival in TCGA patients. Lastly, we investigated the link between and tumor-infiltrating immune cells (TIICs) through CIBERSORT and the "Correlation" module of GEPIA. The association between TACC3 gene expression and drug response was analyzed using the CellMiner database to predict drug sensitivity.

RESULTS

The outcomes illustrated that was upregulated and considerably correlated with dismal prognosis in LUAD patients. Moreover, the multivariate Cox regression analysis depicted as an independent prognostic marker in LUAD patients. It was also revealed that the expression of was related to clinical stage ( = 0.014), age ( = 0.002), and T classification ( ≤ 0.018). Moreover, we discovered that the expression of was considerably linked to a wide range of TIICs, especially the T cells and NK cells. Single-cell results found that TACC3 was mainly expressed in the immune cells (especially tprolif cells) and malignant cells. TACC3 gene expression was positively correlated with TMB and MSI, and TACC3 may provide a prediction of the efficacy of immunotherapy. Moreover, the correlation analysis between TACC3 gene expression and immune checkpoint gene expression revealed that TACC3 may coordinate the activities of these ICP genes in different signal transduction pathways. TACC3 is related to biological progress (BP), cellular component (CC), and molecular function (MF). The pathways involved in the interaction network involving TACC3 include nonhomologous end-joining, RNA transport, pantothenate and CoA biosynthesis, homologous recombination, and nucleotide excision repair. Furthermore, we investigated the association between the expression of TACC3 and the use of antitumor drugs, and TACC3 was positively correlated with response to most drugs.

CONCLUSION

The findings from this research offer robust proof that the expression of could be a prognostic marker correlated with TIICs in LUAD. TACC3 can also provide new ideas for immunotherapy as a potential therapeutic target.

摘要

背景

肺腺癌 (LUAD) 已被认为是人类最常见的侵袭性恶性肿瘤之一。转化酸性卷曲螺旋蛋白 3 () 似乎是一种非小细胞肺癌 (NSCLC) 的可能预后标志物和治疗靶点。然而,在 LUAD 中,尚无关于与免疫疗法或其他治疗干预措施之间的关联的报道。

方法

基于从癌症基因组图谱 (TCGA) - LUAD 获得的数据,我们进行了生物信息学分析。利用 GEPIA 分析 LUAD 中的表达。构建了一个生存模块来评估对 LUAD 患者生存的影响。采用 logistic 回归检验与临床因素的关系。在 GeneMANIA 数据库中进行蛋白质-蛋白质相互作用分析,并在 Gene Ontology 和京都基因与基因组百科全书 (KEGG) 中进行富集分析和预测信号通路的鉴定。此外,采用 Cox 回归评估 TCGA 患者与总生存期相关的临床病理特征。最后,我们通过 CIBERSORT 和 GEPIA 的“Correlation”模块研究了与肿瘤浸润免疫细胞 (TIIC) 的关系。通过 CellMiner 数据库分析 TACC3 基因表达与药物反应的关系,以预测药物敏感性。

结果

结果表明,在 LUAD 患者中,上调并与不良预后显著相关。此外,多变量 Cox 回归分析表明在 LUAD 患者中是独立的预后标志物。还发现的表达与临床分期 ( = 0.014)、年龄 ( = 0.002) 和 T 分类 (=0.018)有关。此外,我们发现的表达与多种 TIIC 显著相关,尤其是 T 细胞和 NK 细胞。单细胞结果发现 TACC3 主要在免疫细胞(尤其是 tprolif 细胞)和恶性细胞中表达。TACC3 基因表达与 TMB 和 MSI 呈正相关,TACC3 可能对免疫治疗的疗效具有预测作用。此外,TACC3 基因表达与免疫检查点基因表达的相关性分析表明,TACC3 可能在不同的信号转导途径中协调这些 ICP 基因的活性。TACC3 与生物学进程 (BP)、细胞成分 (CC) 和分子功能 (MF) 有关。涉及 TACC3 相互作用网络的途径包括非同源末端连接、RNA 转运、泛酸和辅酶 A 生物合成、同源重组和核苷酸切除修复。此外,我们研究了 TACC3 表达与抗肿瘤药物使用之间的关系,发现 TACC3 与大多数药物的反应呈正相关。

结论

本研究结果提供了有力的证据表明,的表达可以作为 LUAD 中与 TIIC 相关的预后标志物。TACC3 也可以作为一种潜在的治疗靶点,为免疫治疗提供新的思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d4c/9288335/f98fd91abf82/DM2022-8789515.001.jpg

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