Yang M, Zhu X, Shen Y, He Q, Qin Y, Shao Y, Yuan L, Ye H
Department of Urology, The Second Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210017, China.
Department of Urology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2022 Aug 20;42(8):1109-1118. doi: 10.12122/j.issn.1673-4254.2022.08.01.
To explore the correlation of MYB proto-oncogene like 2 (MYBL2) with biological behaviors and clinical prognosis of prostate cancer (PCa).
We detected Mybl2 mRNA expression in 45 pairs of PCa and adjacent tissues using real-time quantitative PCR, and analyzed the correlation of high (23 cases) and low expression (22 cases) of with clinicopathological features and prognosis of the patients using nonparametric test, Kaplan-Meier survival analysis and univariate and multivariate Cox regression. The results were verified by analysis of the data from Cancer Genome Atlas (TCGA) microarray database, and the molecular pathways were identified by gene set enrichment analysis (GSEA). The CIBERPORT algorithm was used to identify the correlations between expression and tumor microenvironment of PCa. We also tested the effects of MYBL2 knockdown on proliferation and invasion of PCa cell lines using cell counting kit-8 and Transwell assays and observed the growth of PC3 cell xenograft with MYBL2 knockdown in nude mice and the expression levels of Ki-67 in the xenograft using immunohistochemistry.
expression was significantly elevated in PCa tissues in close correlation with Gleason score and clinical and pathological stage of the tumor ( < 0.01) but not with the patients' age. Kaplan-Meier analysis indicated a significant negative correlation of high expression with recurrence-free survival ( < 0.05), but not with the overall survival of the patients. The data from TCGA suggested that clinical and pathological stages were independent prognostic factors for recurrence-free survival, and our data indicated that clinical stage and Gleason score were independent prognostic factors of PCa ( < 0.05). GSEA suggested that expression was related with the pathways involving immune function, cell adhesion, and cytokine secretion; CIBERPORT analysis suggested the involvement of expression with memory B cells and resting mast cells ( < 0.05). In LNCaP and PC-3 cells, MYBL2 knockdown significantly inhibited cell proliferation and invasion ( < 0.05); in the tumor-bearing nude mice, the xenografts derived from PC-3 cells with MYBL2 knockdown exhibited a lowered mean tumor weight and positivity rate for Ki67 ( < 0.05).
is an oncogene related with multiple pathological indicators of PCa and can serve as a potential prognostic marker as well as a therapeutic target for patients with PCa.
探讨MYB原癌基因样2（MYBL2）与前列腺癌（PCa）生物学行为及临床预后的相关性。
采用实时定量PCR检测45对PCa组织及癌旁组织中Mybl2 mRNA表达水平，运用非参数检验、Kaplan-Meier生存分析以及单因素和多因素Cox回归分析高表达组（23例）和低表达组（22例）与患者临床病理特征及预后的相关性。通过分析癌症基因组图谱（TCGA）微阵列数据库数据对结果进行验证，并采用基因集富集分析（GSEA）鉴定分子通路。运用CIBERPORT算法确定MYBL2表达与PCa肿瘤微环境之间的相关性。使用细胞计数试剂盒-8和Transwell实验检测MYBL2敲低对PCa细胞系增殖和侵袭的影响，并通过免疫组化观察MYBL2敲低的PC3细胞异种移植瘤在裸鼠体内的生长情况及异种移植瘤中Ki-67的表达水平。
PCa组织中MYBL2表达显著升高，与Gleason评分及肿瘤临床病理分期密切相关（P<0.01），但与患者年龄无关。Kaplan-Meier分析表明，MYBL2高表达与无复发生存率呈显著负相关（P<0.05），但与患者总生存率无关。TCGA数据提示临床病理分期是无复发生存的独立预后因素，而本研究数据表明临床分期和Gleason评分是PCa的独立预后因素（P<0.05）。GSEA提示MYBL2表达与免疫功能、细胞黏附及细胞因子分泌相关通路有关；CIBERPORT分析提示MYBL2表达与记忆B细胞和静息肥大细胞有关（P<0.05）。在LNCaP和PC-3细胞中，MYBL2敲低显著抑制细胞增殖和侵袭（P<0.05）；在荷瘤裸鼠中，MYBL2敲低的PC-3细胞异种移植瘤平均瘤重降低，Ki67阳性率降低（P<0.05）。
MYBL2是与PCa多种病理指标相关的癌基因，可作为PCa患者潜在的预后标志物及治疗靶点。
