鉴定参与T1G3期尿路上皮癌（UC）对卡介苗免疫治疗反应的姐妹染色单体黏连与分离（SCCS）/染色质重塑途径中的不同微小RNA（miRNA）及其相关的miRNA靶向基因。
Identification of Different miRNAs and Their Relevant miRNA Targeted Genes Involved in Sister Chromatid Cohesion and Segregation (SCCS)/chromatin Remodeling Pathway on T1G3 Urothelial Carcinoma (UC) Response to BCG Immunotherapy.
作者信息
Awadalla Amira, Zahran Mohamed H, Abol-Enein Hassan, Zekri Abdel-Rahman N, Elbaset Mohamed Abd, Ahmed Asmaa E, Hamam Eman T, Elsawy Amr, Khalifa Mohamed K, Shokeir Ahmed A
机构信息
Center of Excellence for genome and cancer research, Urology and Nephrology Center, Mansoura University, Egypt.
Center of Excellence for genome and cancer research, Urology and Nephrology Center, Mansoura University, Egypt.
出版信息
Clin Genitourin Cancer. 2022 Jun;20(3):e181-e189. doi: 10.1016/j.clgc.2021.12.001. Epub 2021 Dec 16.
BACKGROUND
Till now, no definite clinical or laboratory marker can predict the recurrence or progression of T1 G3 urothelial carcinoma (UC). Genetic aberrations of the chromatin remodeling genes and sister chromatid cohesion and segregation (SCCS) were identified in UC. Here we investigated the impact of novel miRNAs and their targeted expressed SCCS and chromatin remodeling genes on T1G3 UC response to Bacillus Calmette-Guérin (BCG) therapy.
METHODS
One hundred tissue samples were obtained from NMIBC patients. Gene expression and immunohistochemical assay of STAG2, ARID1A, NCOR1and UTX were assessed. MiRNA analysis for their targeting miRNAs (miR-21, miR-31, Let7a and miR-199a) was carried out. Assessed genes were compared between responders and no responders to BCG. Univariate and multivariate analysis of predictors of disease recurrence and progression were performed using cox regression analysis.
RESULTS
Thirty-two and 22 patients developed recurrence and progression to MIBC (BCG non-responders). BCG non-responders showed statistically significant higher expression of miR-21 and their targeted STAG2, miR-199a and NCOR1 gene (P < .001), and lower expression of miR-31, Let7a, ARID1A and UTX genes (P < .001). Higher miR-199a (P = .006) and lower miR-31 (P = .01), ARID1A (P = .008) and UTX (P = .03) were independent predictor of higher tumor recurrence. Recurrent disease (P = .003), higher expression of STAG2 (P = .01), NCOR1 (P = .01) and miR-21 (P = .03) genes and lower expression of miR-31 (P = .02), Let7a (P = .04) and ARID1A (P = .04) genes were the independent predictor of disease progression.
CONCLUSION
Upregulation of STAG2 and NCOR1 and down regulation of ARID1A and UTX genes and their targeting miRNAs were associated with UC non-response to BCG.
背景
迄今为止，尚无明确的临床或实验室标志物能够预测T1 G3尿路上皮癌（UC）的复发或进展。在UC中已发现染色质重塑基因以及姐妹染色单体黏连与分离（SCCS）的基因异常。在此，我们研究了新型微小RNA（miRNA）及其靶向表达的SCCS和染色质重塑基因对T1G3 UC卡介苗（BCG）治疗反应的影响。
方法
从非肌层浸润性膀胱癌（NMIBC）患者中获取100份组织样本。评估STAG2、ARID1A、NCOR1和UTX的基因表达及免疫组化检测结果。对其靶向miRNA（miR-21、miR-31、Let7a和miR-199a）进行miRNA分析。比较BCG治疗反应者与无反应者之间的评估基因。使用Cox回归分析对疾病复发和进展的预测因素进行单因素和多因素分析。
结果
32例和22例患者分别出现复发和进展为肌层浸润性膀胱癌（MIBC，BCG无反应者）。BCG无反应者中miR-21及其靶向的STAG2、miR-199a和NCOR1基因的表达在统计学上显著更高（P <.001），而miR-31、Let7a、ARID1A和UTX基因的表达更低（P <.001）。较高的miR-199a（P =.006）以及较低的miR-31（P =.01）、ARID1A（P =.008）和UTX（P =.03）是肿瘤复发率较高的独立预测因素。复发疾病（P =.003）、较高的STAG2（P =.01）、NCOR1（P =.01）和miR-21（P =.03）基因表达以及较低的miR-31（P =.02）、Let7a（P =.04）和ARID1A（P =.04）基因表达是疾病进展的独立预测因素。
结论
STAG2和NCOR1的上调以及ARID1A和UTX基因及其靶向miRNA的下调与UC对BCG无反应相关。
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