AAT 耐药相关的 AC007405.2 和 AL354989.1 作为前列腺癌的新型诊断和预后标志物。

AAT resistance-related AC007405.2 and AL354989.1 as novel diagnostic and prognostic markers in prostate cancer.

机构信息

Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Yuzhong, Chongqing 400016, China.

Chongqing Key Laboratory of Molecular Oncology and Epigenetics, Yuzhong, Chongqing, China.

出版信息

Aging (Albany NY). 2024 Apr 19;16(8):7249-7266. doi: 10.18632/aging.205754.

DOI:10.18632/aging.205754

PMID:38643469

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11087092/

Abstract

OBJECTIVE

Prostate cancer (PCa) is the second disease threatening men's health, and anti-androgen therapy (AAT) is a primary approach for treating this condition. Increasing evidence suggests that long non-coding RNAs (lncRNAs) play crucial roles in the development of PCa and the process of AAT resistance. The objective of this study is to utilize bioinformatics methods to excavate lncRNAs association with AAT resistance and investigate their biological functions.

METHODS

AAT resistance-related risk score model (ARR-RSM) was established by multivariate Cox analysis. Paired clinical tissue samples of 36 PCa patients and 42 blood samples from patients with PSA over 4 ng/ml were collected to verify the ARR-RSM. , RT-qPCR, CCK-8 and clone formation assays were displayed to verify the expression and function of AL354989.1 and AC007405.2.

RESULTS

Pearson correlation analysis identified 996 lncRNAs were associated with AAT resistance (ARR-LncRs). ARR-RSM was established using multivariate Cox regression analysis, and PCa patients were divided into high-risk and low-risk groups. High-risk patients showed increased expression of AL354989.1 and AC007405.2 had poorer prognoses. The high-risk score correlated with advanced T-stage and -stage. The AUC of ARR-RSM outperformed tPSA in diagnosing PCa. Silencing of AC007405.2 and AL354989.1 inhibited PCa cells proliferation and AAT resistance.

CONCLUSIONS

In this study, we have discovered the clinical significance of AC007405.2 and AL354989.1 in predicting the prognosis and diagnosing PCa patients. Furthermore, we have confirmed their correlation with various clinical features. These findings provide potential targets for PCa treatment and a novel diagnostic and predictive indicator for precise PCa diagnosis.

摘要

目的

前列腺癌（PCa）是威胁男性健康的第二大疾病，抗雄激素治疗（AAT）是治疗该病的主要方法。越来越多的证据表明，长链非编码 RNA（lncRNA）在 PCa 的发展和 AAT 耐药过程中发挥着关键作用。本研究旨在利用生物信息学方法挖掘与 AAT 耐药相关的 lncRNA，并研究其生物学功能。

方法

通过多变量 Cox 分析建立 AAT 耐药相关风险评分模型（ARR-RSM）。收集 36 例 PCa 患者的配对临床组织样本和 42 例 PSA 超过 4ng/ml 的患者血样进行验证。采用 RT-qPCR、CCK-8 和克隆形成实验验证 AL354989.1 和 AC007405.2 的表达和功能。

结果

Pearson 相关性分析鉴定出 996 个与 AAT 耐药相关的 lncRNA（ARR-LncRs）。采用多变量 Cox 回归分析建立 ARR-RSM，将 PCa 患者分为高危和低危组。高危组患者 AL354989.1 和 AC007405.2 表达增加，预后较差。高危评分与晚期 T 分期和 N 分期相关。ARR-RSM 的 AUC 优于 tPSA 诊断 PCa。沉默 AC007405.2 和 AL354989.1 抑制 PCa 细胞增殖和 AAT 耐药。