CHRDL1、NEFH、TAGLN 和 SYNM 作为良性前列腺增生和前列腺癌的新型诊断生物标志物。

CHRDL1, NEFH, TAGLN and SYNM as novel diagnostic biomarkers of benign prostatic hyperplasia and prostate cancer.

机构信息

Department of Urology, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China.

Department of Breast Surgery, Guizhou Provincial People's Hospital, Guiyang, Guizhou, China.

出版信息

Cancer Biomark. 2023;38(2):143-159. doi: 10.3233/CBM-230028.

DOI:10.3233/CBM-230028

PMID:37781794

Abstract

BACKGROUND

Prostate cancer (PCa) and benign prostatic hyperplasia (BPH) are common male diseases whose incidence rates gradually increase with age. They seriously affect men's physical health and quality of life. This study aimed to identify new biomarkers for the diagnosis of BPH and PCa.

METHODS

Two datasets, GSE28204 and GSE134051 (including human PCa and BPH), were downloaded from the GEO database. The batch effect was removed for merging, and then differential gene expression analysis was conducted to identify BPH and PCa cases. The diagnostic biomarkers of BPH and PCa were further screened using machine learning and bioinformatics. ROC curves were drawn to evaluate the diagnostic accuracy of the selected biomarkers. An online website and qPCR were used to preliminarily explore the expression levels of PCa biomarkers. The correlations between the expression of biomarkers and the tumor microenvironment, tumor mutation load and immunotherapy drugs were evaluated.

RESULTS

We identified fifteen genes (CHRDL1, DES, FLNC, GSTP1, MYL9, TGFB3, NEFH, TAGLN, SPARCL1, SYNM, TRPM8, HPN, PLA2G7, ENTPD5 and GPR160) as critical diagnostic biomarkers. After reviewing the literature on all selected biomarkers, we found few studies on the four genes CHRDL1, NEFH, TAGLN and SYNM in BPH or PCa. We defined these four genes as new potential diagnostic biomarkers (NPDBs) of BPH and PCa. All NPDBs were downregulated in PCa patients and PCa cell lines and upregulated in BPH patients and cell lines. When the immune landscape and mutation frequencies were analyzed, the results showed that the tumor microenvironment (TME), immune landscape, tumor mutation burden, and drug response were significantly correlated with NPDB expressions.

CONCLUSIONS

We found four new diagnostic markers of BPH and PCa, which may facilitate the early diagnosis, treatment, and immunotherapeutic responses assessment and may be of major value in guiding clinical practice.

摘要

背景

前列腺癌（PCa）和良性前列腺增生（BPH）是常见的男性疾病，其发病率随着年龄的增长逐渐增加。它们严重影响男性的身体健康和生活质量。本研究旨在寻找用于诊断 BPH 和 PCa 的新生物标志物。

方法

从 GEO 数据库中下载了两个数据集 GSE28204 和 GSE134051（包括人类 PCa 和 BPH），并去除了批次效应进行合并，然后进行差异基因表达分析以鉴定 BPH 和 PCa 病例。进一步使用机器学习和生物信息学筛选 BPH 和 PCa 的诊断生物标志物。绘制 ROC 曲线以评估所选生物标志物的诊断准确性。使用在线网站和 qPCR 初步探索 PCa 生物标志物的表达水平。评估生物标志物的表达与肿瘤微环境、肿瘤突变负荷和免疫治疗药物之间的相关性。

结果

我们确定了 15 个关键的诊断生物标志物（CHRDL1、DES、FLNC、GSTP1、MYL9、TGFB3、NEFH、TAGLN、SPARCL1、SYNM、TRPM8、HPN、PLA2G7、ENTPD5 和 GPR160）。在对所有选定的生物标志物进行文献回顾后，我们发现关于 BPH 或 PCa 中四个基因 CHRDL1、NEFH、TAGLN 和 SYNM 的研究很少。我们将这四个基因定义为 BPH 和 PCa 的新潜在诊断生物标志物（NPDBs）。所有 NPDB 在 PCa 患者和 PCa 细胞系中下调，在 BPH 患者和细胞系中上调。当分析免疫景观和突变频率时，结果表明肿瘤微环境（TME）、免疫景观、肿瘤突变负担和药物反应与 NPDB 表达显著相关。