Yu Seong Hyeon, Kim Sung Sun, Lee Hyungki, Kim Shinseung, Kang Taek Won
Department of Urology, Chonnam National University Medical School, Chonnam National University Hospital, Gwangju 61469, Republic of Korea.
Department of Pathology, Chonnam National University Medical School, Chonnam National University Hospital, Gwangju 61469, Republic of Korea.
Diagnostics (Basel). 2023 Oct 13;13(20):3201. doi: 10.3390/diagnostics13203201.
Next-generation sequencing (NGS) is widely used in muscle-invasive bladder cancer but has limited use in non-muscle-invasive bladder cancer (NMIBC) due to significant heterogeneity and high cancer-specific survival. Therefore, we evaluated the genomic information of NMIBC and identified molecular alterations associated with tumour recurrence. A total of 43 patients with NMIBC who underwent transurethral resection of the bladder were enrolled. We performed NGS using an Oncomine panel of tumour specimens and blood samples corresponding to each specimen. The somatic mutation results were analysed by pairwise comparison and logistic regression according to the recurrence of bladder tumours within 1 year. The median incidence of genetic variations in 43 tumour samples was 56 variations per sample, and a high tumour mutation burden (TMB) was associated with tumour recurrence (median variation 33 vs. 64, = 0.023). The most mutated gene was adipose tissue macrophages () (79%), followed by neurofibromatosis-1 () (79%), and neurogenic locus notch homolog protein 1 () (79%). In multivariable analysis, mutation of epidermal growth factor receptor () (odds ratio [OR], 9.95; 95% confidence interval [CI], 1.40-70.96; = 0.022) and telomerase reverse transcriptase (TERT) (OR, 7.92; 95% CI, 1.22-51.51; = 0.030) were significant factors associated with the recurrence of bladder tumour within 1 year. Our results revealed that high TMB, EGFR mutation, and TERT mutation had a significant association with tumour recurrence in NMIBC. In addition, somatic mutations in EGFR and TERT could be useful prognostic biomarkers in NMIBC.
下一代测序（NGS）在肌肉浸润性膀胱癌中广泛应用，但由于显著的异质性和较高的癌症特异性生存率，在非肌肉浸润性膀胱癌（NMIBC）中的应用有限。因此，我们评估了NMIBC的基因组信息，并确定了与肿瘤复发相关的分子改变。共有43例接受膀胱经尿道切除术的NMIBC患者入组。我们使用肿瘤标本的Oncomine检测板和与每个标本对应的血液样本进行了NGS。根据膀胱肿瘤1年内的复发情况，通过成对比较和逻辑回归分析体细胞突变结果。43个肿瘤样本中基因变异的中位发生率为每个样本56个变异，高肿瘤突变负担（TMB）与肿瘤复发相关（中位变异数33对64，P = 0.023）。突变最多的基因是脂肪组织巨噬细胞（ADAMTS1）（79%），其次是神经纤维瘤病1型（NF1）（79%）和神经源性位点Notch同源蛋白1（NOTCH1）（79%）。在多变量分析中，表皮生长因子受体（EGFR）突变（比值比[OR]，9.95；95%置信区间[CI]，1.40 - 70.96；P = 0.022）和端粒酶逆转录酶（TERT）突变（OR，7.92；95%CI，1.22 - 51.51；P = 0.030）是与膀胱肿瘤1年内复发相关的显著因素。我们的结果显示，高TMB、EGFR突变和TERT突变与NMIBC的肿瘤复发显著相关。此外，EGFR和TERT的体细胞突变可能是NMIBC中有用的预后生物标志物。
