Xu Xinyu, Yan Minyu, Xie Zhiwen, Zhang Yongqing, Wu Lei, Zhang Bimeng, Jiang Juntao
Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Acupuncture, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China.
Transl Cancer Res. 2025 Jul 30;14(7):4194-4207. doi: 10.21037/tcr-24-2013. Epub 2025 Jul 22.
Extensive evidence has demonstrated a robust association between high infiltration of M2 macrophages and the prognosis of bladder cancer (BLCA). Nevertheless, no comprehensive analysis of co-expressed M2 genes in BLCA has been reported. We would like to develop a prognostic model for BLCA using M2 co-expressed genes.
Raw data and clinical characteristics were retrieved from public databases. We first used the "cibersort" package to determine the M2 macrophage infiltration coefficients of each BLCA sample in The Cancer Genome Atlas (TCGA). Subsequently, Pearson correlation was employed to screen co-expressed genes based on the coefficients. Least absolute shrinkage and selection operator (LASSO-COX) analysis was then employed to construct the prognostic gene signature, which was externally validated in the GSE13507 cohort. Further exploration of the signature involved tumor mutational burden (TMB) and drug sensitivity analyses. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) was employed to validate the expression levels of the co-expressed genes.
We developed a signature using two co-expressed genes and utilized it to categorize samples into two groups. Patients in the low-risk group exhibited more satisfactory outcomes (P=0.008) and higher TMB (P=0.04). Additionally, the high-risk group exhibited a substantial discrepancy in immune subtypes compared to the low-risk group, as indicated by the significantly elevated levels of resting CD4 memory T cells, M0, and M2.
We constructed a prognostic signature for BLCA based on two co-expressed genes. The performance of this signature was validated in both TCGA and GSE13507, indicating its potential usefulness in predicting the prognosis of BLCA and developing new therapeutic methods.
大量证据表明M2巨噬细胞的高浸润与膀胱癌（BLCA）的预后之间存在密切关联。然而，尚未有关于BLCA中共表达M2基因的综合分析报道。我们希望利用M2共表达基因开发一种BLCA的预后模型。
从公共数据库中检索原始数据和临床特征。我们首先使用“cibersort”软件包确定癌症基因组图谱（TCGA）中每个BLCA样本的M2巨噬细胞浸润系数。随后，基于这些系数采用Pearson相关性分析来筛选共表达基因。接着采用最小绝对收缩和选择算子（LASSO-COX）分析构建预后基因特征，并在GSE13507队列中进行外部验证。对该特征的进一步探索包括肿瘤突变负荷（TMB）和药物敏感性分析。最后，采用定量实时聚合酶链反应（qRT-PCR）验证共表达基因的表达水平。
我们利用两个共表达基因开发了一种特征，并将样本分为两组。低风险组的患者表现出更满意的预后（P=0.008）和更高的TMB（P=0.04）。此外，高风险组与低风险组相比，免疫亚型存在显著差异，静止CD4记忆T细胞、M0和M2的水平显著升高。
我们基于两个共表达基因构建了BLCA的预后特征。该特征在TCGA和GSE13507中均得到验证，表明其在预测BLCA预后和开发新治疗方法方面具有潜在用途。
