Bioinformatics analysis of the clinical value and potential mechanisms of AHNAK2 in papillary thyroid carcinoma

Abstract

Background: AHNAK2 has been recently reported as a biomarker in many cancers. However, a systematic investigation of AHNAK2 in papillary thyroid carcinoma (PTC) has not been conducted. Results: AHNAK2 is overexpressed in PTC tissues and could be an independent prognostic factor. AHNAK2 expression was significantly high in patients with advanced stage, advanced T classification, lymph node metastasis, increased BRAF mutations and decreased RAS mutations. Cell adhesion-, cell junction-, and immune-related pathways were the most frequently noted in gene set enrichment analysis. AHNAK2 expression in PTC was positively correlated with immune infiltration and negatively correlated with AHNAK2 methylation. AHNAK2 expression was significantly positively correlated with tumor progression and poor overall survival (OS) in pan-cancer patients. Conclusions: AHNAK2 is a good biomarker for the diagnosis and prognosis of PTC. AHNAK2 may promote thyroid cancer progression through cell adhesion-, cell junction-, and immune-related pathways. Methylation may act as an upstream regulator to inhibit the expression and biological function of AHNAK2 . Additionally, AHNAK2 has broad prognostic value in pan-cancer. Methods: Based on The Cancer Genome Atlas (TCGA) data, we screened AHNAK2 -related genes through weighted gene coexpression network analysis and explored the clinical value and the potential mechanism of AHNAK2 in PTC by multiomics analysis.

Prognostic Impact of AHNAK2 Expression in Patients Treated with Radical Cystectomy

“…As a diagnostic marker, AHNAK2 could immunohistochemically differentiate between inflammatory changes and carcinoma in situ (CIS) [ 18 ]. In terms of the prognostic value, only a few studies have been performed and reported that a higher expression of AHNAK2 was associated with shorter overall survival in BCa [ 13 , 19 ]. However, these previous studies were based on gene enrichment analyses and focused on an association between gene types and survival duration without adjusting clinical information.…”

“…Pan-cancer analyses revealed the functional roles of AHNAK2 in the epithelial-mesenchymal transition (EMT), which plays a key role as a tumor promoter by allowing epithelial cells to gain a range of mesenchymal characteristics [ 13 , 14 ]. Analyses based on clinical specimens showed that AHNAK2 regulated the EMT via a TGF-β/Smad3 pathway in lung adenocarcinoma and a hypoxia inducible factor-1α/zinc finger E-box-binding homeobox 1 (HIF-1/ZEB1) pathway in clear cell renal cell carcinoma [ 10 , 16 ].…”

“…AHNAK2, also known as C14orf78, is a member of the AHNAK family and was originally found in mouse heart tissue extract, encoding a giant protein of more than 600 kilodaltons (kDa) [ 9 ]. Over the last seven years, overexpression of AHNAK2 has been reported to be associated with poor prognosis in clear cell renal cell carcinoma, pancreatic ductal adenocarcinoma, uveal melanoma, papillary thyroid carcinoma, and lung adenocarcinoma [ 10 , 11 , 12 , 13 , 14 ]. Furthermore, previous studies indicated AHNKA2 as a possible new therapeutic target in some cancers because it would play an important role in regulating multiple tumor progression pathways, including mitogen - activated protein kinase (MAPK) / extracellular signal - regulated kinase (ERK) , phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT), hypoxia inducible factor-1α (HIF-1α), and transforming growth factor-β (TGF-β)/Smad3 [ 10 , 12 , 15 , 16 ].…”

Aberrant expression of PROS1 correlates with human papillary thyroid cancer progression

“…Several bioinformatics reports have identified the important roles of immune-related biomarkers in PTC pathogenesis, such as AHNAK nucleoprotein 2 (AHNAK2), angiotensin II receptor type 1 (AGTR1), etc. ( Li et al, 2021 ; Lin et al, 2019 ; Xie et al, 2020b ; Xue, Li & Lu, 2020 ). In patients with PTC, M2 macrophages, Tregs, monocytes, neutrophils, DCs, MCs, and M0 macrophages appeared to play a tumor-promoting role, while M1 macrophages, CD8 + T cells, B cells, NK cells, and T follicular helper (TFH) cells might play an anti-tumor part ( Xie et al, 2020a ).…”

<p>AHNAK2 Promotes Migration, Invasion, and Epithelial-Mesenchymal Transition in Lung Adenocarcinoma Cells via the TGF-β/Smad3 Pathway</p>

“…Two members comprise the AHNAK protein family, which are AHNAK and AHNAK2: 5 AHNAK plays a protective role in vascular healing after wire injury and contributes to muscular dystrophies when it is abnormally located in muscle connective tissues, 6,7 whereas AHNAK2, originally found in mouse heart tissue extract and gradually reported in recent years, 5 is involved in cell migration, repair and other processes. [8][9][10][11] AHNAK2 is regarded as an oncogenic protein and plays a role in the metastases of cancers, including pancreatic ductal adenocarcinoma, clear cell renal cell carcinoma, uveal melanoma, and papillary thyroid carcinoma, [12][13][14][15] and some studies have revealed its possible mechanism in tumors. Kirov et al have indicated that AHNAK2 is an important element of the fibroblast growth factor1 nonclassical export pathway, which regulates carcinogenesis, angiogenesis, and inflammation, 16 Li et al reported that it promotes uveal melanoma progression by regulating the PI3K signaling pathway, 14 and Wang et al revealed that AHNAK2 mediates hypoxia pathway-driven epithelial-mesenchymal transition (EMT) and induction of stem cell properties by targeting hypoxia-inducible factor 1 (HIF1)-α in clear cell renal cell carcinoma.…”