What question did this study set out to answer?

The research aimed to identify prognostic genes linked to immunogenic cell death in thyroid cancer.

July 12, 2026BMC Cancer0 citationsOpen Access

CXCR6 and its correlated G protein-coupled receptors and PI3K-AKT pathways were associated with the progression of thyroid cancer

YYYiting YaoNanjing University of Chinese Medicine LHLinlang HuangGeneral Hospital of Guangzhou Military Command RXRui XiaNanjing University of Chinese Medicine

Key Points

The research aimed to identify prognostic genes linked to immunogenic cell death in thyroid cancer.
Single-cell analysis to identify distinct cell types relevant to immunogenic cell death.
Prognostic model developed using 101 combinations of 10 algorithms to analyze survival disparities.
Real-time RT-qPCR and Western blot analysis were conducted to assess expression patterns of key genes and associated pathways.
Identified CXCR6 and four other prognostic genes associated with immunogenic cell death in thyroid cancer.
StepCox + Random Survival Forest model yielded the highest C-index for predicting survival outcomes.
Found decreased CXCR6 expression in thyroid cancer samples, correlating with pathological changes in the PI3K-AKT signaling pathway.

Abstract

Abstract Background Immunogenic cell death (ICD) is closely linked to thyroid cancer (THCA). We mined ICD-linked prognostic genes for survival predictors and unpacked their potential biology. Materials Single-cell analysis was conducted to identify distinct cell types, and the scores of ICD-related genes (ICDRGs) were computed to identify key cell types. Furthermore, correlation, differential expression, and Kaplan-Meier survival studies were conducted to discover prognostic genes. By employing these genes alongside 101 combinations of 10 algorithms, we constructed a prognostic model and computed risk scores for THCA samples, analyzing their survival disparities. Control and THCA tissue samples were taken to assess the expression of prognostic genes via real-time reverse transcriptase-polymerase chain reaction (RT-qPCR), resulting in the identification of a key gene. Subsequently, gene set enrichment analysis was executed on this key gene, and Western blot analysis was undertaken to evaluate the expression of relevant pathways. Results Single-cell and transcriptome analysis found CXCR6, ICOS, SLAMF7, CD80, and TNF as prognostic genes associated with ICD in THCA. Of the 101 combinations evaluated, the StepCoxboth + Random Survival Forest (RSF) model was selected as the prognostic model owing to its superior C-index. This model accurately forecasted survival outcomes for THCA samples. Expression study demonstrated a notable decrease of CXCR6 in THCA samples, consistent with bioinformatics analysis and it was designated as the key gene. Functional analysis revealed an enrichment of the inflammatory response, accompanied by reduced levels of its principal targets (Gαi) and downstream pathways (Src and PI3K-AKT) in THCA samples. Conclusion This study found five prognostic genes, with CXCR6 associated with Gαi, Src, and PI3K-AKT pathways in the modulation of THCA, indicating the essential function of CXCR6 in THCA.

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