Unveiling the Crucial Role of H۱۹ in Testicular Germ Cell Tumor Invasion and Metastasis through Integrated High-Throughput Sequencing Analysis

: The intricate world of long noncoding RNAs (lncRNAs) has emerged as a focal point in understanding diverse physiological and pathological processes. However, their significance in testicular germ cell tumors (TGCT) remains largely uncharted. This study aims to delve deeply into the expression patterns and functional implications of lncRNAs in TGCT, unraveling their potential roles in disease progression. Material and methods: Utilizing RNA sequencing, we meticulously examined lncRNA expression profiles across ۱۳ TGCT tissues and ۴ paraneoplastic tissues, offering a panoramic view of lncRNA involvement in TGCT pathogenesis. Our approach encompassed rigorous bioinformatics analyses, unveiling significant differential expression of numerous lncRNAs in TGCT. Furthermore, through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, we elucidated the intricate involvement of these dysregulated lncRNAs in various biological processes linked with tumorigenesis, both through cis and trans-regulatory mechanisms. Results: Our scrutiny highlighted H۱۹ as a pivotal player in TGCT progression. Employing weighted gene co-expression network analysis (WGCNA) and mining the Gene Expression Profiling Interactive Analysis (GEPIA) database, we discerned a positive correlation between H۱۹ expression levels and poor prognosis, as well as the pathological grade of TGCT. Subsequent in vitro experiments provided mechanistic insights, demonstrating that H۱۹ fosters the migration and invasion of TGCT cells by modulating the expression of AKT۳ and influencing total AKT phosphorylation. Further scrutiny of The Cancer Genome Atlas (TCGA) data revealed a negative correlation between H۱۹ expression and immune cell infiltration, along with the response to PD۱ immunotherapy, suggesting H۱۹'s potential as both a prognostic marker and a predictor of immunotherapeutic response in TGCT. Conclusion: In summary, our study marks the inaugural comprehensive exploration of lncRNA expression profiles in TGCT, unearthing the metastasis-promoting role of H۱۹. These revelations offer invaluable insights for the development of prognostic markers and therapeutic targets, potentially revolutionizing the diagnosis and treatment of TGCT metastasis. Through our meticulous analysis, we bridge the gap in understanding the molecular underpinnings of TGCT and pave the way for personalized therapeutic interventions tailored to combat this formidable disease.

کلیدواژه ها:

Spermatozoa ، Protamine ، Methyltransferase ، Single-Cell RNA Sequencing ، Spermatogenesis