Abstract
Background Lung adenocarcinoma (LUAD), as the main subtype of lung cancer, is one of the common causes of cancer-related deaths worldwide. The AHNAK family is correlated with cell structure and migration, cardiac calcium channel signaling, and tumor metastasis. Previous studies showed AHNAK2 could promote tumor progression and cell migration in melanoma and renal clear cell carcinoma. However, the role of AHNAK2 in LUAD remains unknown. Methods We examined the levels of AHNAK2 in pathological specimens and the database of Clinical Proteomic Tumor Analysis Consortium-Lung adenocarcinoma (CPTAC-LUAD), The Cancer Genome Atlas-Lung Adenocarcinoma (TCGA-LUAD), Gene Expression Omnibus dataset (GSE72094, GSE26939), and The Genotype-Tissue Expression (GTEx) of lung tissue samples. Univariate Cox regression, multivariate Cox regression, and Kaplan–Meier survival analysis were performed to reveal the relationship between AHNAK2 and prognosis. A nomogram was constructed to predict 2- or 3-year overall survival and validated via calibration curves, receiver operating characteristic (ROC) analysis, and decision curve analysis (DCA). Furthermore, Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to explore the functional role of AHNAK2 in lung adenocarcinoma. Finally, by transfecting siRNA, we examined the regulatory effect of AHNAK2 on cell migration. Results The expression of AHNAK2 was upregulated in tumor samples and correlated with poor prognosis in LUAD patients. Nomogram with AHNAK2 and clinical parameters showed a good prediction in overall survival (OS), especially the 2-year OS. In addition, functional analyses and wound healing assay suggested that AHNAK2 might be involved in the regulation of migration in LUAD. Conclusion In summary, our study showed that AHNAK2 might be a novel biomarker in LUAD and revealed the potential mechanism of AHNAK2 in LUAD progression which could provide new insights for target therapy.
Highlights
Lung cancer is one of the most common cancers that seriously threaten human health [1, 2]
Our findings showed that AHNAK2 could be a novel prognostic marker and therapeutic target of lung adenocarcinoma
AHNAK2 Upregulated in Lung Adenocarcinoma Samples and Associated with Poor Prognosis
Summary
Lung cancer is one of the most common cancers that seriously threaten human health [1, 2]. One authoritative statistical survey on lung cancer showed that there were 2.09 million new patients and more than 1.76 million deaths worldwide in 2018, ranking first in both the incidence and mortality [3]. The overall survival rate of lung adenocarcinoma is not significantly upgraded [7]. Lung adenocarcinoma (LUAD), as the main subtype of lung cancer, is one of the common causes of cancer-related deaths worldwide. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to explore the functional role of AHNAK2 in lung adenocarcinoma. Nomogram with AHNAK2 and clinical parameters showed a good prediction in overall survival (OS), especially the 2-year OS. Our study showed that AHNAK2 might be a novel biomarker in LUAD and revealed the potential mechanism of AHNAK2 in LUAD progression which could provide new insights for target therapy
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