Anoikis resistance promotes prostate cancer progression via conferring immune evasion
Objective To investigate the impact and mechanisms of anoikis resistance and immune microenvironment interactions on tumor progression in prostate cancer.Methods Single-cell transcriptom-ic data from 13 prostate cancer patients,downloaded from GSE141445,were analyzed to identify two tumor cell subgroups,Anoikis-Epi and Resistance-Epi,based on anoikis activity scores.Differences in intercel-lular communication between the subgroups and T cells were compared to explore how Resistance-Epi af-fects T cells.Validation was conducted using prostate cancer anoikis-resistant cell lines.Immune infiltra-tion was evaluated using TIMER and ESTIMATE tools,and its correlation with anoikis resistance scores was analyzed.Finally,genes associated with anoikis resistance were identified through differential analysis and examined for clinical relevance via survival analysis.Results Based on Anoikis scoring,tumor cells of the luminal subtype and Intermediate subtype were defined as Anoikis-Epi and Resistance-Epi,respec-tively.Clinical correlation analysis revealed that anoikis resistance was associated with tumor progression(Gleason score,P＜0.01;T stage,P＜0.01;M stage,P＜0.05)and poorer survival outcomes(P＜0.05).Resistance-Epi exhibited a loss of human leukocyte antigen(HLA)class Ⅰ expression,a finding validated in prostate cancer anoikis-resistant cell lines.Bulk data analysis revealed a significant positive correlation between anoikis scores and immune infiltration levels(R=0.34,P＜0.01).Lastly,combined single-cell and bulk data analyses identified OGN as a potential marker of anoikis resistance.OGN expres-sion was significantly reduced in anoikis-resistant cell lines(t=3.47,P＜0.05)and positively correlated with immune infiltration(R=0.38,P＜0.01).Survival analysis of TCGA dataset showed that patients with low OGN expression had worse progression-free survival compared to those with high expression(x2=13.2,P＜0.01).Conclusion Resistance to anoikis mediates the loss of human leukocyte antigens(HLA),weakens T cell immunity,and promotes prostate cancer progression by inducing immune evasion.
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