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术前荧光原位杂交分析预测非肌肉浸润性膀胱癌患者肿瘤复发:一项双机构研究。

Preoperative fluorescence in situ hybridization analysis as a predictor of tumor recurrence in patients with non-muscle invasive bladder cancer: a bi-institutional study.

机构信息

Department of Urology, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangdong Provincial Clinical Research Center for Urological Diseases, 107 Yan Jiang West Road, Guangzhou, People's Republic of China.

Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yan Jiang West Road, Guangzhou, People's Republic of China.

出版信息

J Transl Med. 2023 Oct 2;21(1):685. doi: 10.1186/s12967-023-04528-2.

DOI:10.1186/s12967-023-04528-2
PMID:37784106
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10546664/
Abstract

BACKGROUND

Non-muscle invasive bladder cancer (NMIBC) is known for its elevated recurrence rate, necessitating an enhancement in the current risk stratification for recurrence. The urine-based fluorescence in situ hybridization (FISH) assay has emerged as a noninvasive auxiliary tool for detecting bladder cancer. The aim of this study was to explore the potential relationship between the preoperative FISH assay and recurrence, and to develop a FISH-clinical nomogram for predicting the recurrence-free survival (RFS) in NMIBC patients.

METHODS

In total, 332 eligible patients were enrolled from two hospitals. The SYSMH cohort was randomly assigned to the training set (n = 168) and the validation set I (n = 72) at a ratio of 7:3, while the SYSUTH cohort was allocated to the validation set II (n = 92). The correlation between the preoperative FISH assay and recurrence was determined through the Cox regression analysis. The least absolute shrinkage and selection operator (LASSO) Cox regression algorithm was used for model construction. The performance of the model was assessed by its discrimination, calibration, and clinical usefulness.

RESULTS

We uncovered that chromosome 7 aneuploidy, p16 locus loss, number of the positive FISH sites, and the FISH test result were significantly associated with tumor recurrence. Then, a FISH-clinical nomogram incorporating the FISH test result, T stage, associated CIS, tumor grade, and tumor status was developed. It showed favorable calibration and discrimination with a C-index of 0.683 (95%CI, 0.611-0.756) in the training set, which was confirmed in the validation set I and validation set II with C-indexes of 0.665 (95%CI, 0.565-0.765) and 0.778 (95%CI, 0.665-0.891), respectively. Decision curve analysis revealed the clinical usefulness of the nomogram. Moreover, our proposed nomogram significantly outperformed the guideline-recommended EORTC and CUETO scoring models.

CONCLUSION

Our study confirmed the prognostic value of the preoperative FISH assay and proposed a FISH-clinical nomogram to predict RFS in NMIBC patients. Our nomogram can serve as a more precise tool for recurrence risk stratification, which may optimize disease management in bladder cancer and improve patient prognosis.

摘要

背景

非肌肉浸润性膀胱癌(NMIBC)以其高复发率为特征,需要对目前的复发风险分层进行改进。基于尿液的荧光原位杂交(FISH)检测已成为一种用于检测膀胱癌的非侵入性辅助工具。本研究旨在探讨术前 FISH 检测与复发之间的潜在关系,并为 NMIBC 患者建立预测无复发生存(RFS)的 FISH-临床列线图。

方法

共纳入来自两家医院的 332 名合格患者。SYSMH 队列按 7:3 的比例随机分配至训练集(n=168)和验证集 I(n=72),而 SYSUTH 队列分配至验证集 II(n=92)。通过 Cox 回归分析确定术前 FISH 检测与复发之间的相关性。采用最小绝对收缩和选择算子(LASSO)Cox 回归算法进行模型构建。通过区分度、校准度和临床实用性评估模型的性能。

结果

我们发现染色体 7 非整倍体、p16 位点缺失、阳性 FISH 位点数量和 FISH 检测结果与肿瘤复发显著相关。然后,建立了一个包含 FISH 检测结果、T 分期、相关 CIS、肿瘤分级和肿瘤状态的 FISH-临床列线图。该列线图在训练集中的校准度和区分度良好,C 指数为 0.683(95%CI,0.611-0.756),在验证集 I 和验证集 II 中得到验证,C 指数分别为 0.665(95%CI,0.565-0.765)和 0.778(95%CI,0.665-0.891)。决策曲线分析显示了该列线图的临床实用性。此外,我们提出的列线图显著优于指南推荐的 EORTC 和 CUETO 评分模型。

结论

本研究证实了术前 FISH 检测的预后价值,并提出了一种 FISH-临床列线图来预测 NMIBC 患者的 RFS。我们的列线图可以作为复发风险分层的更精确工具,从而优化膀胱癌的疾病管理并改善患者的预后。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee35/10546664/5c91539355c9/12967_2023_4528_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee35/10546664/a45dfa2f3d8b/12967_2023_4528_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee35/10546664/6d1c0bccabc5/12967_2023_4528_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee35/10546664/ea2e198b394b/12967_2023_4528_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee35/10546664/415a27a1440c/12967_2023_4528_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee35/10546664/5c91539355c9/12967_2023_4528_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee35/10546664/a45dfa2f3d8b/12967_2023_4528_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee35/10546664/6d1c0bccabc5/12967_2023_4528_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee35/10546664/ea2e198b394b/12967_2023_4528_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee35/10546664/415a27a1440c/12967_2023_4528_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee35/10546664/5c91539355c9/12967_2023_4528_Fig5_HTML.jpg

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