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IF 9.1 1区医学 Q1 ONCOLOGY Cancer letters Pub Date : 2024-09-13 DOI:10.1016/j.canlet.2024.217259

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引用次数: 0

摘要

背景不同的肾细胞癌（RCC）患者在组织形态学、蛋白质组遗传改变、免疫细胞浸润模式和临床表现方面表现出很大的异质性。本研究旨在通过对十个样本（四个正常样本、三个透明细胞肾细胞癌（ccRCC）样本和三个嗜色细胞肾细胞癌（chRCC）样本）进行单核测序，揭示 RCC 患者的致病起源和预后特征。此外，我们还通过基于摘要数据的孟德尔随机化和共定位方法，在基因水平上探索致病因素。根据相关的恶性标志物，共比较了 212 种机器学习组合，从而建立了一个具有高精度和高稳定性的预后特征。最后，该研究与临床数据相关联，调查哪些细胞亚型可能影响患者的预后。结果& 结论确定了两种主要来源的肿瘤细胞：近端肾小管细胞 B 型和间质细胞 A 型是高度分化的上皮细胞，三个基因位点被确定为潜在的致病基因。在 212 个预后模型中，最佳恶性特征对 ccRCC 具有很高的预测能力：（AUC：训练数据集为 0.920（1 年）、0.920（3 年）和 0.930（5 年）；测试数据集为 0.756（1 年）、0.828（3 年）和 0.832（5 年）。此外，我们还证实，LYVE1+组织驻留巨噬细胞和TOX+ CD8对ccRCC患者的预后有显著影响，而单核细胞对chRCC患者的预后起着关键作用。

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Single-nucleus sequencing unveils heterogeneity in renal cell carcinomas microenvironment: Insights into pathogenic origins and treatment-responsive cellular subgroups

Background

Different individuals with renal cell carcinoma (RCC) exhibit substantial heterogeneity in histomorphology, genetic alterations in the proteome, immune cell infiltration patterns, and clinical behavior.

Objectives

This study aims to use single-nucleus sequencing on ten samples (four normal, three clear cell renal cell carcinoma (ccRCC), and three chromophobe renal cell carcinoma (chRCC)) to uncover pathogenic origins and prognostic characteristics in patients with RCC.

Methods

By using two algorithms, inferCNV and k-means, the study explores malignant cells and compares them with the normal group to reveal their origins. Furthermore, we explore the pathogenic factors at the gene level through Summary-data-based Mendelian Randomization and co-localization methods. Based on the relevant malignant markers, a total of 212 machine-learning combinations were compared to develop a prognostic signature with high precision and stability. Finally, the study correlates with clinical data to investigate which cell subtypes may impact patients’ prognosis.

Results & conclusion

Two main origin tumor cells were identified: Proximal tubule cell B and Intercalated cell type A, which were highly differentiated in epithelial cells, and three gene loci were determined as potential pathogenic genes. The best malignant signature among the 212 prognostic models demonstrated high predictive power in ccRCC: (AUC: 0.920 (1-year), 0.920 (3-year) and 0.930 (5-year) in the training dataset; 0.756 (1-year), 0.828 (3-year), and 0.832 (5-year) in the testing dataset. In addition, we confirmed that LYVE1⁺ tissue-resident macrophage and TOX⁺ CD8 significantly impact the prognosis of ccRCC patients, while monocytes play a crucial role in the prognosis of chRCC patients.

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来源期刊

Cancer letters 医学-肿瘤学

CiteScore

17.70

自引率

2.10%

发文量

427

审稿时长

15 days

期刊介绍： Cancer Letters is a reputable international journal that serves as a platform for significant and original contributions in cancer research. The journal welcomes both full-length articles and Mini Reviews in the wide-ranging field of basic and translational oncology. Furthermore, it frequently presents Special Issues that shed light on current and topical areas in cancer research. Cancer Letters is highly interested in various fundamental aspects that can cater to a diverse readership. These areas include the molecular genetics and cell biology of cancer, radiation biology, molecular pathology, hormones and cancer, viral oncology, metastasis, and chemoprevention. The journal actively focuses on experimental therapeutics, particularly the advancement of targeted therapies for personalized cancer medicine, such as metronomic chemotherapy. By publishing groundbreaking research and promoting advancements in cancer treatments, Cancer Letters aims to actively contribute to the fight against cancer and the improvement of patient outcomes.