Xu Zhenglin, Zhang Qi, Luh Frank, Jin Baiye, Liu Xiyong
Department of Urology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, P.R. China.
Department of Urologic Surgery, Affiliated Dongyang People's Hospital of Wenzhou Medical University, Dongyang, Zhejiang 322100, P.R. China.
Oncol Lett. 2019 Feb;17(2):1865-1876. doi: 10.3892/ol.2018.9762. Epub 2018 Nov 26.
Abnormal spindle-like microcephaly-associated () protein is essential for mitotic spindle function during cell replication. The present study aimed to evaluate the hypothesis that serves a critical role in cancer invasiveness and may act as a prognostic biomarker in bladder cancer. In total, 6 independent worldwide bladder cancer microarray mRNA expression datasets (n=1,355) with clinical and follow-up annotations were collected from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Reverse transcription-quantitative polymerase chain reaction analysis revealed that mRNA expression was higher in bladder cancer tissue compared with adjacent normal bladder mucosae in 10 paired human tissue samples (P=0.004). overexpression in human bladder cancer samples was consistent with the mRNA expression datasets from GEO and TCGA. Bioinformatics analysis indicated that mRNA expression was significantly associated with grade and tumor node metastasis (TNM) stage in bladder cancer, based on pooled GEO and TCGA datasets (P<0.05). Stratification analysis indicated that the clinical significance of was particularly pronounced in low-grade or papillary subtypes of bladder cancer. Individual Cox and pooled Kaplan-Meier analyses suggested that expression was significantly directly correlated with poor overall (OS) and progression-free survival (PFS) in bladder cancer. Multivariate and stratification analyses demonstrated that the prognostic significance of was evident in low-grade or papillary bladder cancers, yet not in high-grade or non-papillary subgroups. Increased expression of was associated with poor OS in muscle-invasive bladder cancer and with poor PFS in non-muscle-invasive bladder cancer (P<0.05). Bioinformatics analysis identified the top 11 -related genes on STRING-DB.org. The expression of the majority of these genes was associated with poor outcomes of bladder cancer with statistical significance. Gene set enrichment analysis indicated that the high expression of could enrich gene signatures involved in mitosis, differentiation and metastasis in bladder cancer. Further analysis of TCGA datasets indicated that increased expression was significantly associated with higher Gleason score, T stage, N stage and poor clinical outcome in prostate cancer. It was also significantly associated with late TNM stage and poor PFS in renal cell carcinoma. In summary, may serve as a novel prognostic biomarker for low-grade or papillary bladder cancer.
异常纺锤样小头畸形相关()蛋白在细胞复制过程中的有丝分裂纺锤体功能中至关重要。本研究旨在评估这一假说,即该蛋白在癌症侵袭中起关键作用,并可能作为膀胱癌的预后生物标志物。总共从基因表达综合数据库(GEO)和癌症基因组图谱(TCGA)数据库中收集了6个独立的全球膀胱癌微阵列mRNA表达数据集(n = 1355),并带有临床和随访注释。逆转录定量聚合酶链反应分析显示,在10对人组织样本中,膀胱癌组织中的该蛋白mRNA表达高于相邻正常膀胱黏膜(P = 0.004)。人膀胱癌样本中的该蛋白过表达与来自GEO和TCGA的mRNA表达数据集一致。生物信息学分析表明,基于汇总的GEO和TCGA数据集,该蛋白mRNA表达与膀胱癌的分级和肿瘤淋巴结转移(TNM)分期显著相关(P < 0.05)。分层分析表明,该蛋白的临床意义在膀胱癌的低级别或乳头状亚型中尤为明显。个体Cox分析和汇总的Kaplan-Meier分析表明,该蛋白表达与膀胱癌的总体生存期(OS)和无进展生存期(PFS)差显著直接相关。多变量和分层分析表明,该蛋白的预后意义在低级别或乳头状膀胱癌中明显,但在高级别或非乳头状亚组中不明显。该蛋白表达增加与肌层浸润性膀胱癌的OS差以及非肌层浸润性膀胱癌的PFS差相关(P < 0.05)。生物信息学分析在STRING-DB.org上确定了前11个与该蛋白相关的基因。这些基因中的大多数表达与膀胱癌的不良预后具有统计学意义相关。基因集富集分析表明,该蛋白的高表达可富集膀胱癌中与有丝分裂、分化和转移相关的基因特征。对TCGA数据集的进一步分析表明,该蛋白表达增加与前列腺癌的更高 Gleason评分、T分期、N分期和不良临床结局显著相关。它也与肾细胞癌的晚期TNM分期和不良PFS显著相关。总之,该蛋白可能作为低级别或乳头状膀胱癌的新型预后生物标志物。