Key Laboratory of Cancer Prevention and Therapy of Tianjin, Department of Colorectal Cancer Surgery, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300202, China.
Key Laboratory of Cancer Prevention and Therapy of Tianjin, Department of Pancreatic Cancer Surgery, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300202, China.
Curr Med Chem. 2024;31(30):4912-4934. doi: 10.2174/0929867331666230821092346.
Single-cell technology enables a deep study on the mechanism of cancers. This work delineated the function of ligand-receptor interaction in colon adenocarcinoma (COAD), and developed a LR pairs-based prognostic model.
For identifying important LR pairs, Single-cell RNA sequencing data of COAD was included. Unsupervised consensus clustering constructed molecular subtypes. LASSO established a prognostic model. Infiltration of 22 immune cells was evaluated by Cibersort. Enrichment score of oxidative stress related pathways was determined by SsGSEA in each patient.
Forty-seven LR pairs were closely associated with the prognosis of COAD. Three molecular subtypes were differentiated according to 47 LR pairs, which displayed differential clinical features and molecular features. There were significant differences in immune T cell lytic activity among different subtypes. In clust1 with poor prognosis, significantly enriched oncogenic pathways were found, especially epithelial-mesenchymal transition (EMT). Additionally, it has been found that clust3 had significantly higher immune infiltration. A prognostic model containing eight LR pairs (PDGFB-PDGFRA, FLT4-VEGFC, CSF1R-CSF1, DLL1-NOTCH4, PDGFB-LRP1, DLL1- NOTCH3, FLT4-PDGFC, and NRP2-PGF) was established, which could effectively divide samples into low-risk and high-risk groups. Significantly higher oxidative stress was found among high-risk patients.
This study integrated expression data and single-cell data for demonstrating the effectiveness of LR pairs in establishing the prognostic model and constructing molecular subtypes. Prognostic LR pairs may contribute to tumorigenesis and progression in COAD. The prognostic model was the potential for predicting prognosis and guiding immunotherapy for COAD patients.
单细胞技术使我们能够深入研究癌症的机制。本研究描绘了配体-受体相互作用在结肠腺癌（COAD）中的功能，并建立了基于 LR 对的预后模型。
纳入 COAD 的单细胞 RNA 测序数据，以鉴定重要的 LR 对。无监督共识聚类构建分子亚型。LASSO 建立预后模型。通过 Cibersort 评估 22 种免疫细胞的浸润。通过 SsGSEA 确定每个患者氧化应激相关途径的富集评分。
鉴定出 47 对与 COAD 预后密切相关的 LR 对。根据 47 对 LR 对，区分出 3 个分子亚型，它们显示出不同的临床特征和分子特征。不同亚型之间的免疫 T 细胞溶解活性存在显著差异。在预后不良的 clust1 中，发现了明显富集的致癌途径，特别是上皮-间充质转化（EMT）。此外，发现 clust3 具有更高的免疫浸润。包含 8 对 LR 对（PDGFB-PDGFRA、FLT4-VEGFC、CSF1R-CSF1、DLL1-NOTCH4、PDGFB-LRP1、DLL1-NOTCH3、FLT4-PDGFC 和 NRP2-PGF）的预后模型能够有效地将样本分为低风险和高风险组。高危患者的氧化应激明显升高。
本研究整合了表达数据和单细胞数据，证明了 LR 对在建立预后模型和构建分子亚型方面的有效性。预后 LR 对可能有助于 COAD 的肿瘤发生和进展。该预后模型有可能预测 COAD 患者的预后并指导免疫治疗。
