Lin Quanjun, Wang Zhiqiang, Wang Jue, Xu Ming, Zhang Xinyi, Sun Peng, Yuan Yihang
Department of General Surgery, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Clinical Medical College, Southwest Medical University, Luzhou, China.
Front Immunol. 2024 Dec 9;15:1509658. doi: 10.3389/fimmu.2024.1509658. eCollection 2024.
Colorectal cancer (CRC) is a leading cause of cancer-related deaths globally. The heterogeneity of the tumor microenvironment significantly influences patient prognosis, while the diversity of tumor cells shapes its unique characteristics. A comprehensive analysis of the molecular profile of tumor cells is crucial for identifying novel molecular targets for drug sensitivity analysis and for uncovering the pathophysiological mechanisms underlying CRC.
We utilized single-cell RNA sequencing technology to analyze 13 tissue samples from 4 CRC patients, identifying key cell types within the tumor microenvironment. Intercellular communication was assessed using CellChat, and a risk score model was developed based on eight prognostic genes to enhance patient stratification for immunotherapeutic approaches. Additionally, experiments were performed on , a gene strongly associated with poor prognosis, to validate its potential role as a therapeutic target in CRC progression.
Eight major cell types were identified across the tissue samples. Within the tumor cell population, seven distinct subtypes were recognized, with the C0 + tumor cells subtype being significantly linked to cancer progression and poor prognosis. CellChat analysis indicated extensive communication among tumor cells, fibroblasts, and immune cells, underscoring the complexity of the tumor microenvironment. The risk score model demonstrated high accuracy in predicting 1-, 3-, and 5-year survival rates in CRC patients. Enrichment analysis revealed that the C0 + tumor cell subtype exhibited increased energy metabolism, protein synthesis, and oxidative phosphorylation, contributing to its aggressive behavior. experiments confirmed as a critical gene associated with poor prognosis, suggesting its viability as a target for improving drug sensitivity.
In summary, this study advances our understanding of CRC progression by identifying critical tumor subtypes, molecular pathways, and prognostic markers that can inform innovative strategies for predicting and enhancing drug sensitivity. These findings hold promise for optimizing immunotherapeutic approaches and developing new targeted therapies, ultimately aiming to improve patient outcomes in CRC.
结直肠癌（CRC）是全球癌症相关死亡的主要原因。肿瘤微环境的异质性显著影响患者预后，而肿瘤细胞的多样性塑造了其独特特征。全面分析肿瘤细胞的分子特征对于确定药物敏感性分析的新分子靶点以及揭示CRC潜在的病理生理机制至关重要。
我们利用单细胞RNA测序技术分析了4例CRC患者的13个组织样本，确定了肿瘤微环境中的关键细胞类型。使用CellChat评估细胞间通讯，并基于8个预后基因建立风险评分模型，以加强免疫治疗方法的患者分层。此外，对一个与预后不良密切相关的基因进行了实验，以验证其在CRC进展中作为治疗靶点的潜在作用。
在组织样本中鉴定出8种主要细胞类型。在肿瘤细胞群体中，识别出7种不同的亚型，其中C0 +肿瘤细胞亚型与癌症进展和预后不良显著相关。CellChat分析表明肿瘤细胞、成纤维细胞和免疫细胞之间存在广泛通讯，突显了肿瘤微环境的复杂性。风险评分模型在预测CRC患者1年、3年和5年生存率方面显示出高准确性。富集分析显示，C0 +肿瘤细胞亚型表现出能量代谢、蛋白质合成和氧化磷酸化增加，这有助于其侵袭性行为。实验证实该基因是与预后不良相关的关键基因，表明其作为提高药物敏感性靶点的可行性。
总之，本研究通过确定关键的肿瘤亚型、分子途径和预后标志物，推进了我们对CRC进展的理解，这些标志物可为预测和提高药物敏感性的创新策略提供依据。这些发现有望优化免疫治疗方法并开发新的靶向治疗，最终目标是改善CRC患者的预后。
