Biomedical subjects

Ankui Yang

Publications and source records attributed to Ankui Yang.

2 recordsLinked to original sources

PubMed2026

SERPINE1-centric inflammatory signature associates with treatment resistance and survival in laryngeal squamous cell carcinoma.

BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) prognosis remains poor despite treatment advances. More accurate prognostic assessment models can help guide individualized treatment and improve prognosis. Chronic inflammation contributes to tumorigenesis, yet inflammatory response-related genes (IRGs) in LSCC prognosis are underexplored. This study aimed to construct an IRG prognostic signature for LSCC and further dissect core IRG-mediated mechanisms of immune escape and chemoresistance. METHODS: Transcriptional profiles and clinical data from LSCC patients were retrieved from The Cancer Genome Atlas (TCGA). IRGs were sourced from Gene Set Enrichment Analysis (GSEA) hallmark gene set. We identified differentially expressed IRGs linked to survival outcomes in LSCC. Key IRGs were subsequently selected using least absolute shrinkage and selection operator (LASSO) Cox regression analysis to establish an inflammatory risk score model. This model underwent internal validation within the TCGA cohort and external validation using independent Gene Expression Omnibus (GEO) datasets. We further assessed the model's association with the tumor immune microenvironment and the impact of IRGs on chemotherapy response. Finally, the functional roles of interested signature IRG were experimentally validated in LSCC cell lines. RESULTS: Four significant IRGs (AQP9, ITGA5, LCK, SERPINE1) were identified to build the risk score model. The model stratified LSCC patients into distinct prognostic groups: TCGA cohort: 5-year area under the curve (AUC) =0.836, P<0.001; GSE25727 cohort: 5-year AUC =0.706, P=0.02; GSE27020 cohort: 5-year AUC =0.798, P<0.01. Multivariate analysis confirmed the risk score as an independent prognostic factor (P<0.05). High-risk patients showed reduced immune cell infiltration (CD8+ T cells, dendritic cells) and suppressed immune pathways. Multi-algorithm immune analysis further revealed defective antigen presentation and reduced anti-tumor immune infiltration in high-risk LSCC, promoting tumor immune escape. GSEA/Gene Ontology (GO) enrichment combined with drug sensitivity prediction further revealed that high-risk tumors activate invasive signaling and acquire broad chemoresistance alongside impaired anti-tumor immunity. SERPINE1 might be associated with chemotherapy resistance and exhibited the highest alteration frequency (predominantly amplification) and overexpression in LSCC tissues. Its knockdown significantly suppressed proliferation, migration, invasion and chemoresistance in LSCC cells. Immunohistochemistry (IHC) confirmed tumor SERPINE1 overexpression (P=0.002 vs. normal tissues), correlating with poor survival (P<0.001). CONCLUSIONS: The 4-IRG risk signature is a reliable prognostic indicator reflecting immune dysfunction in LSCC. SERPINE1 is validated as a therapeutic target and biomarker, enriching our understanding of gene regulation dynamics in LSCC.

Laryngeal cancer↗

PubMed2026

A pan-cancer single-cell atlas uncovers the role of sex hormones and chromosomes in sex-divergent reprogramming of the tumor microenvironment.

BACKGROUND: Sex bias is pervasive in tumors; however, how sex chromosomes and hormone-responsive signaling shape the tumor microenvironment (TME) remains insufficiently characterized. Considering the critical impact of the TME on tumor progression and response to immunotherapy, a pan-cancer investigation of sex-specific and cancer-context-dependent TME features is warranted. METHOD: Based on stringent inclusion criteria, we constructed a high-resolution pan-cancer single-cell sequencing atlas by integrating 31 publicly available single-cell RNA-seq datasets, comprising a total of 1,831,436 cells by integrating 468 samples from eight types of non-sex-specific solid tumors (282 males and 186 females). After correcting for batch effects, we identified major and minor cellular subsets. Multiple computational approaches were applied to investigate sex-associated differences in cellular composition, gene expression, pathway activity, malignant cell states and intercellular communication. RESULTS: We systematically compared sex-specific TME features across eight common solid malignancies. Male-biased CD8+ T cell exhaustion emerged as a recurrent but non-uniform feature, with its magnitude varying across cancer types and being modified by tissue-specific contexts. This pattern was associated with androgen-response signature scores and expression-based loss of the Y chromosome (LOY) scores. M2-like macrophage polarization showed a more cancer-type-dependent pattern; although female-biased enrichment was observed in selected malignancies, it did not represent a uniform pan-cancer feature. Expression-based X chromosome inactivation (XCI)/XCI escape-related programs, estrogen-response signature scores and stromal components, including fibroblasts and endothelial cells, were associated with macrophage and immune-regulatory states in specific tumor contexts. Tumor cells of male origin displayed higher genomic instability and more aggressive phenotypes, with androgen-response signatures and LOY contributing to the development of a male biased malignant state. Furthermore, expression-based LOY scores in malignant cells were associated with CD8+ T cell exhaustion based on transcriptomic proxies. CONCLUSION: Our study uncovers extensive but heterogeneous sex-specific differences in the TME across multiple cancer types. We propose a regulatory framework linking sex chromosomes, hormone-responsive signaling and TME interactions, which is consistent with recurrent male-biased CD8⁺ T cell exhaustion and context-dependent M2-like macrophage polarization. Importantly, the magnitude and, in some cancers, the direction of these sex-biased features are modified by tissue-specific contexts. These findings underscore the need to include sex chromosome and hormone status as essential biological variables in studies of the tumor microenvironment and the design of immunotherapies.

Tumor Microenvironment↗