通过单细胞 RNA 测序和基因共表达网络发现与结肠腺癌中 CD8(+) T 细胞浸润和肿瘤相关纤维化相关的生物标志物

Colorectal adenocarcinoma (COAD) is a prevalent malignant tumor associated with a high mortality rate. Within the tumor microenvironment, CD8 + T cells play a pivotal role in the anti-tumor immune response within the human body. Fibrosis directly and indirectly affects the therapeutic response of tumor immunotherapy. However, the significance of regulatory genes associated with tumor-associated fibrosis and CD8 + T cell infiltration remains uncertain. Therefore, it is imperative to identify biomarkers with prognostic value and elucidate the precise role of CD8 + T cells and tumor-associated fibrosis.

We performed a single-cell transcriptome analysis of COAD samples from the GEO database. To evaluate immune infiltration in COAD samples, we utilized CIBERSORT and ESTIMATE. Furthermore, we analyzed the correlation between CD8 + T cells and immune infiltration. To analyze COAD expression's quantitative immune cell composition data, we conducted a Weighted Gene Correlation Network Analysis and utilized a deconvolution algorithm. The data for these analyses were obtained from the GEO database. We utilized univariate Cox regression and LASSO analysis to create a prognostic model. The predictive model was assessed through Kaplan-Meier analysis, and a survival prediction nomogram was created. Additionally, we analyzed the correlation between the prognostic model and chemotherapy drug sensitivity. To estimate the expression of hub genes, we employed immunohistochemistry, real-time PCR, and western blot techniques.

Single-cell transcriptome analysis has indicated a higher prevalence of CD8 + T cells in COAD tumor samples. The connection between COAD and CD8 + T cells was further confirmed by WGCNA and deconvolution analysis using the GEO database. The Protein-Protein Interaction network analysis revealed three hub genes: LARS2 , SEZ6L2 , and SOX7 . A predictive model was subsequently created using LASSO and univariate COX regression, which included these three genes. Two of these hub genes ( LARS2 and SEZ6L2 ) were found to be upregulated in COAD cell lines and tissues, while SOX7 was observed to be downregulated. The prognostic model demonstrated a significant association with CD8 + T cells, suggesting that these genes could serve as potential biomarkers and targets for gene therapy in treating COAD.

This study has identified three key genes associated with CD8 + T cells and the prognosis of COAD, providing new prognostic biomarkers for diagnosing and treating COAD.