双硫死亡相关基因在结直肠癌中的表达及其临床意义

陈晓玲; 吕敏敏; 李燕; 贾亦真

doi:10.13406/j.cnki.cyxb.003566

重庆医科大学学报 ›› 2024, Vol. 49 ›› Issue (08) : 1018 -1024. DOI: 10.13406/j.cnki.cyxb.003566

生物信息学

双硫死亡相关基因在结直肠癌中的表达及其临床意义

陈晓玲 ¹ ,
吕敏敏 ² ,
李燕 ¹ ,
贾亦真 ³

作者信息 +

Expression and clinical significance of disulfidptosis-related genes in colorectal cancer

Author information +

文章历史 +

PDF (4133K)

摘要

目的识别双硫死亡相关基因在结直肠癌中的表达模式。方法严格选出TCGA数据库中结直肠癌样本开展差异基因分析，并与已报道文献中的双硫基因取交集，筛选出双硫死亡相关结直肠癌差异基因，在GEO数据库和人类蛋白图谱（human protein atlas，HPA）数据库上进一步验证了双硫死亡相关基因的表达，对基因SLC7A11在人结直肠癌样本中的表达进行了qPCR验证。下载GSE184093数据集，利用上述筛选获得的基因作为标记，设置不同的阈值对癌症和对照样本进行分类，并使用ROC曲线下面积（area under the curve，AUC）评估分类效果。通过K-M生存分析，鉴定标记基因对患者总体生存率的影响，利用TIMER数据库分析标记基因的表达与免疫细胞浸润的相关性。结果识别出了2个与结直肠癌相关的双硫死亡相关基因。SLC7A11和SLC3A2这2个双硫死亡相关基因均在结直肠癌患者中高表达，并且SLC7A11高表达，结直肠癌患者预后良好，差异有统计学意义（P<0.05）；SLC3A2高表达，结直肠癌患者预后较差，但是差异无统计学意义（P=0.061）。使用SLC7A11和SLC3A2作为标记，对样本进行分类鉴别结直肠癌，通过ROC曲线图可以发现，SLC7A11和SLC3A2对结直肠癌鉴别诊断的AUC分别为0.840（95%CI=0.663~1.000）和0.667（95%CI=0.395~0.938），SLC7A11对鉴别诊断结直肠癌具有一定的准确性，SLC3A2对鉴别诊断结直肠癌具有较低的准确性。SLC7A11和SLC3A2在结直肠癌的免疫浸润中起着重要的作用，SLC7A11表达与结肠腺癌中的CD8⁺T细胞、中性粒细胞、树突状细胞浸润水平正相关（P<0.001），SLC7A11表达与直肠癌的CD8⁺T细胞、中性粒细胞浸润水平正相关（P<0.001）。SLC3A2表达与结肠腺癌的CD8⁺T细胞、B细胞浸润水平负相关（P<0.01），与结肠腺癌的CD4⁺T细胞正相关（P<0.05）。结论本研究发现，SLC7A11和SLC3A2这2个双硫死亡相关基因均在结直肠癌患者中高表达，并与结直肠癌免疫浸润密切相关，且SLC7A11对结直肠癌鉴别诊断具有一定的准确性，为结直肠癌提供了可靠和潜在的治疗靶点。

Abstract

Objective To identify the expression patterns of disulfidptosis-related genes in colorectal cancer. Methods Colorectal cancer samples in the TCGA database were selected for the analysis of differentially expressed genes，which were intersected with the disulfide genes reported in the literature to obtain the disulfidptosis-related differentially expressed genes in colorectal cancer. The expression of disulfidptosis-related genes was further verified based on GEO database and the human protein atlas database，and qPCR was used to verify the expression of the SLC7A11 gene in human colorectal cancer samples. The GSE184093 dataset was downloaded，and the genes obtained from the above screening were used as markers. Different thresholds were set to classify cancer and control samples，and the area under the ROC curve（AUC） was used to evaluate the classification effect. The Kaplan-Meier survival analysis was used to investigate the effect of marker genes on the overall survival rate of patients，and the TIMER database was used to investigate the correlation between the expression of marker genes and immune cell infiltration. Results Two disulfidptosis-related genes were identified to be associated with colorectal cancer. The two disulfidptosis-related genes SLC7A11 and SLC3A2 were highly expressed in colorectal cancer patients，and the colorectal cancer patients with a high expression level of SLC7A11 tended to have a good prognosis（P<0.05），while those with a high expression level of SLC3A2 tended to have a poor prognosis（P=0.061）. With SLC7A11 and SLC3A2 as markers，the samples were classified to identify colorectal cancer. The ROC curve showed that SLC7A11 and SLC3A2 had an AUC of 0.840（95%CI=0.663-1.000） and 0.667（95%CI=0.395-0.938），respectively，in the differential diagnosis of colorectal cancer，and SLC7A11 showed a certain accuracy in the differential diagnosis of colorectal cancer，while SLC3A2 showed a low accuracy. SLC7A11 and SLC3A2 played an important role in the immune infiltration of colorectal cancer； the expression of SLC7A11 was positively correlated with the infiltration of CD8⁺ T cells，neutrophils，and dendritic cells in colon adenocarcinoma（P<0.001），and the expression of SLC7A11 was positively correlated with the infiltration of CD8⁺ T cells and neutrophils in rectal cancer（P<0.001）. The expression of SLC3A2 was negatively correlated with the infiltration of CD8⁺T cells and B cells in colon adenocarcinoma（P<0.01） and was positively correlated with CD4⁺ T cells in colon adenocarcinoma（P<0.05）. Conclusion Our study shows that the two disulfidptosis-related genes SLC7A11 and SLC3A2 are highly expressed in colorectal cancer patients and are closely associated with the immune infiltration of colorectal cancer，and SLC7A11 has a certain accuracy in the differential diagnosis of colorectal cancer，which provides reliable and potential therapeutic targets for colorectal cancer.