结合临床和功能研究发现CSRP1作为激素敏感性前列腺癌的新生物标志物。

IF 5.3 2区 医学 Q1 ONCOLOGY
Chenxi Pan, Wei Wang, Yi He, Bo Yang
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引用次数: 0

摘要

前列腺癌(PCa)是男性癌症相关死亡的第二大常见恶性肿瘤和第五大主要原因。一个关键的挑战在于准确识别那些从激素敏感型PCa (HSPC)迅速过渡到致死性去势抵抗型PCa (CRPC)的高风险患者。在我们的研究中,我们采用多组学方法,包括对数据集GSE2443和GSE35988进行生物信息学分析,以及蛋白质组学研究,发现富含半胱氨酸和甘氨酸的蛋白1 (CSRP1)表达显著影响HSPC的进展。这一假设通过PC3和LNCaP前列腺癌细胞实验得到证实,我们进行了划痕实验和细胞凋亡实验,都证实了CSRP1在抑制肿瘤生长中的作用。此外,我们通过阉割小鼠模型的异种移植实验阐明了CSRP1对肿瘤的抑制作用。为了在临床背景下巩固这些发现,我们构建了一个整合CSRP1免疫组织化学数据和HSPC患者实际队列临床参数的nomogram模型。该模型显示,低CSRP1表达确实促进了向CRPC的发展。综上所述,CSRP1的表达水平可以作为临床医生预测患者疾病进展的有价值的生物标志物。它具有指导个性化临床管理和决策策略的潜力,从而有助于为HSPC患者提供更有效和有针对性的治疗方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Identification of CSRP1 as novel biomarker for hormone-sensitive prostate cancer by the combination of clinical and functional research.

Prostate cancer (PCa) ranks as the second most common malignancy and the fifth leading cause of cancer-related deaths among men. A critical challenge lies in accurately identifying those patients at high risk for transitioning rapidly from hormone-sensitive PCa (HSPC) to lethal castration-resistant PCa (CRPC). In our study, we employed a multiomics approach involving bioinformatics analysis on datasets GSE2443 and GSE35988, along with proteomics studies, to discover that cysteine- and glycine-rich protein 1 (CSRP1) expression significantly impacts the progression of HSPC. This hypothesis was substantiated through experiments using PC3 and LNCaP prostate cancer cells, where we conducted scratch assays and apoptosis assays, all of which confirmed CSRP1's role in suppressing tumor growth. Furthermore, we elucidated the inhibitory effect of CSRP1 on tumors by performing xenograft experiments on castrated mice models. To solidify these findings in a clinical context, we constructed a nomogram model integrating CSRP1's immunohistochemistry data and clinical parameters from an actual patient cohort with HSPC. This model revealed that low CSRP1 expression indeed promotes the advancement towards CRPC. In conclusion, the level of CSRP1 expression can serve as a valuable biomarker for clinicians to predict disease progression in their patients. It has the potential to guide personalized clinical management and decision-making strategies, thereby contributing to more effective and targeted treatment approaches for HSPC patients.

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来源期刊
CiteScore
10.90
自引率
1.70%
发文量
360
审稿时长
1 months
期刊介绍: Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques. The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors. Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.
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