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肺腺癌中预后标志物 AHNAK2 与免疫浸润的相关性。

Correlation between prognostic indicator AHNAK2 and immune infiltrates in lung adenocarcinoma.

机构信息

Department of Pathology, Affiliated Hospital of Nantong University and Medical School of Nantong University, Nantong 226001, Jiangsu, China.

Department of Chemotherapy, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China.

出版信息

Int Immunopharmacol. 2021 Jan;90:107134. doi: 10.1016/j.intimp.2020.107134. Epub 2020 Nov 7.

Abstract

BACKGROUND

Lung adenocarcinoma (LUAD) is among the most aggressive malignant tumors in humans. Although AHNAK nucleoprotein 2 (AHNAK2) is considered a new oncogene, the function of the AHNAK2 in LUAD remains unknown.

METHODS

Oncomine, Tumor Immune Estimation Resource (TIMER), and Human Protein Atlas databases were used to investigate AHNAK2 expression in LUAD. Gene Expression Profiling Interactive Analysis and Kaplan-Meier plotter databases were employed to elucidate the relationship between AHNAK2 and survival time. Data of The Cancer Genome Atlas were downloaded to analyze the correlation between AHNAK2 and clinicopathological parameters. We then immunohistochemically stained tissue chips to further confirm the correlation and conducted Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and protein-protein interaction network analyses to explore the possible functional mechanism of AHNAK2. Finally, we investigated the relationship between AHNAK2 and tumor infiltrating immune cells (TIICs).

RESULTS

AHNAK2 gene was significantly overexpressed in LUAD tumor tissues and an independent prognostic indicator of LUAD patients. The expression of AHNAK2 was related to disease stage, differentiation, tumor size and lymph node metastasis. We found AHNAK2 expression was mainly positively correlated with cell adhesion-related pathways and negatively correlated with oxidative phosphorylation and amino acid metabolism. AHNAK2 expression was also negatively correlated with activated B cell, activated CD8 + T cell, and immature B cell infiltrates and positively correlated with central memory CD4 + T cell, tumor-associated macrophage, M1 macrophage, and M2 macrophage infiltrates.

CONCLUSION

Our findings provide strong evidence of AHNAK2 expression as a prognostic indicator related to TIICs in LUAD.

摘要

背景

肺腺癌(LUAD)是人类最具侵袭性的恶性肿瘤之一。虽然 AHNAK 核蛋白 2(AHNAK2)被认为是一种新的癌基因,但 AHNAK2 在 LUAD 中的功能尚不清楚。

方法

使用 Oncomine、肿瘤免疫估计资源(TIMER)和人类蛋白质图谱数据库来研究 LUAD 中 AHNAK2 的表达。使用基因表达谱交互式分析和 Kaplan-Meier 绘图器数据库来阐明 AHNAK2 与生存时间之间的关系。下载癌症基因组图谱的数据来分析 AHNAK2 与临床病理参数之间的相关性。然后我们通过免疫组织化学染色组织芯片进一步确认相关性,并进行基因本体论、京都基因与基因组百科全书和蛋白质-蛋白质相互作用网络分析,以探索 AHNAK2 的可能功能机制。最后,我们研究了 AHNAK2 与肿瘤浸润免疫细胞(TIIC)之间的关系。

结果

AHNAK2 基因在 LUAD 肿瘤组织中显著过表达,是 LUAD 患者的独立预后指标。AHNAK2 的表达与疾病分期、分化、肿瘤大小和淋巴结转移有关。我们发现 AHNAK2 表达主要与细胞黏附相关途径呈正相关,与氧化磷酸化和氨基酸代谢呈负相关。AHNAK2 表达还与激活的 B 细胞、激活的 CD8+T 细胞和未成熟 B 细胞浸润呈负相关,与中央记忆 CD4+T 细胞、肿瘤相关巨噬细胞、M1 巨噬细胞和 M2 巨噬细胞浸润呈正相关。

结论

我们的研究结果提供了强有力的证据,表明 AHNAK2 表达作为与 LUAD 中 TIIC 相关的预后指标。

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