Affiliation:
1. Fuyang Hospital of Anhui Medical University
2. The First Affiliated Hospital of Anhui Medical University
Abstract
Abstract
Background
Stomach adenocarcinoma (STAD), the most common histologic type of gastric cancer (GC), has unclear molecular mechanisms. A-kinase anchoring protein 8 (AKAP8L) is significantly linked to various tumor processes, including immune invasion and metabolism. However, the role of AKAP8L in STAD development remains enigmatic. This study illuminates AKAP8L’s molecular mechanism, metabolic implications in STAD progression, and potential as a prognostic biomarker.
Methods
Employing diverse databases (TCGA, TIMER, GEPIA, Human Protein Atlas, GSEA), we examined the AKAP8L-STAD correlation. Comparative AKAP8L mRNA/protein analysis was conducted in STAD vs. normal tissues. Immunohistochemistry assays validated the findings in stomach samples from STAD patients. The connection of AKAP8L to clinical attributes is revealed. The prognostic potential was assessed via Kaplan‒Meier analysis and Cox regression. AKAP8L’s link to STAD immune cell infiltration was explored through TIMER. STRING was used to construct the AKAP8L-binding protein network. The R package clusterProfiler enriches AKAP8L’s functions. Immune infiltration’s relationship with AKAP8L in STAD was analyzed via the single-sample GSEA (ssGSEA) method from the R package GSVA and the TIMER database. The diagnostic potential of AKAP8L was assessed using the receiver operating characteristic (ROC) curve, quantified by the area under the curve (AUC) score.
Results
Pancancer analysis revealed upregulated AKAP8L expression in STAD tissues compared to normal tissues, with elevated expression correlated with poor prognosis. The ROC curve indicated that the possible diagnostic biomarker AKAP8L (AUC = 0.821) might exist. Low survival, tumor stage, sample type, subgroup, tumor grade, and lymph node metastasis are all related to higher AKAP8L expression. AKAP8L was connected with tumor-infiltrating lymphocytes (TILs), including immune supporting cells and immunosuppressive cells, and was substantially linked with several immunological marker sets in STAD. Further enrichment analysis showed that the carcinogenicity of AKAP8L may be related to "phosphoinositide metabolism", which provides a novel idea for treating STAD.
Conclusion
In STAD development, upregulated AKAP8L emerges as a key factor associated with immune cell infiltration levels and cellular metabolism. AKAP8L may hold promise as a biomarker, prognostically signifying a more unfavorable outcome for individuals afflicted by STAD.
Publisher
Research Square Platform LLC
Reference29 articles.
1. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries;Sung H;CA: a cancer journal for clinicians 2021
2. Mapping the genomic diaspora of gastric cancer;Yeoh KG;Nat reviews Cancer 2022
3. Role of A-kinase anchoring proteins in cyclic-AMP-mediated Schwann cell proliferation;Asirvatham AL;Cell Signal,2021
4. Expression and humoral response of A-kinase anchor protein 4 in cervical cancer;Agarwal S;Int J Gynecol cancer: official J Int Gynecol Cancer Soc,2013
5. The role of A-kinase anchoring proteins in cancer development;Reggi E;Cell Signal,2017