Miaosen Zheng1, Jian Liu2, Tingting Bian3, Lei Liu3, Hui Sun3, Haomiao Zhou4, Cui Zhao4, Zheng Yang4, Jiahai Shi5, Yifei Liu6. 1. Department of Pathology, Affiliated Hospital of Nantong University and Medical School of Nantong University, Nantong 226001, Jiangsu, China. 2. Department of Chemotherapy, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China. 3. Department of Pathology, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China. 4. Medical School of Nantong University, Nantong 226001, Jiangsu, China. 5. Department of Thoracic Surgery, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China. Electronic address: ntshijiahai0513@163.com. 6. Department of Pathology, Affiliated Hospital of Nantong University and Medical School of Nantong University, Nantong 226001, Jiangsu, China. Electronic address: ntdxliuyifei@sina.com.
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.
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.