Comprehensive analyses of solute carrier family members identify SLC12A2 as a novel therapy target for colorectal cancer

作者：Danyang Chen, Yangyang Zhang, Hai-hang Nie, Haizhou Wang, Peishan Qiu, Fan Wang, Yanan Peng, Fei Xu, Qiu Zhao, Meng Zhang · 发表于：Scientific Reports · 年份：2024 · DOI：10.1038/s41598-024-55048-y · 被引用次数：12 · 研究领域：Cancer, Lipids, and Metabolism、Ferroptosis and cancer prognosis、Epigenetics and DNA Methylation

As the largest transporter family impacting on tumor genesis and development, the prognostic value of solute carrier (SLC) members has not been elucidated in colorectal cancer (CRC). We aimed to identify a prognostic signature from the SLC members and comprehensively analyze their roles in CRC. Firstly, we downloaded transcriptome data and clinical information of CRC samples from GEO (GSE39582) and TCGA as training and testing dataset, respectively. We extracted the expression matrix of SLC genes and established a prognostic model by univariate and multivariate Cox regression. Afterwards, the low-risk and high-risk group were identified. Then, the differences of prognosis traits, transcriptome features, clinical characteristics, immune infiltration and drug sensitivity between the two groups were explored. Furthermore, molecular subtyping was also implemented by non-negative matrix factorization (NMF). Finally, we studied the expression of the screened SLC genes in CRC tumor tissues and normal tissues as well as investigated the role of SLC12A2 by loss of function and gain of function. As a result, we developed a prognostic risk model based on the screened 6-SLC genes (SLC39A8, SLC2A3, SLC39A13, SLC35B1, SLC4A3, SLC12A2). Both in the training and testing sets, CRC patients in the high-risk group had the poorer prognosis and were in the more advanced pathological stage. What's more, the high-risk group were enriched with CRC progression signatures and immune infiltration. Two ...