Individualized prognosis stratification in muscle invasive bladder cancer: A pairwise TP53-derived transcriptome signature

Liu, Huaping; Jia, Wei; Kadeerhan, Gaohaer; Xue, Bai; Guo, Wenmin; Lü, Ning; Wang, Xiaoliang; Wu, Xiaolin; Li, Haitao; Tian, Jun; Wang, Dongwen; Lai, Hung-Ming

doi:10.1016/j.tranon.2023.101629

Cited by 3 publications

(1 citation statement)

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“…This observation is consistent with previous findings that TP53 is the most frequently mutated gene with the highest number of mutations in MIBC. TP53 loss-of-function mutations cause genomic instability and serve as drivers of MIBC [15,28]. While TP53 loss-of-function mutations are known drivers of aggressive bladder cancer [29], mutations in TP53 have not previously been associated with early disease or identified as risk factors in the normal urothelium.…”

Section: Discussionmentioning

confidence: 99%

Mutation Hotspots Found in Bladder Cancer Aid Prediction of Carcinogenic Risk in Normal Urothelium

Grant

Tang

Foster

et al. 2023

IJMS

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More than 80,000 new cases of bladder cancer are estimated to be diagnosed in 2023. However, the 5-year survival rate for bladder cancer has not changed in decades, highlighting the need for prevention. Numerous cancer-causing mutations are present in the urothelium long before signs of cancer arise. Mutation hotspots in cancer-driving genes were identified in non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) tumor samples. Mutation burden within the hotspot regions was measured in normal urothelium with a low and high risk of cancer. A significant correlation was found between the mutation burden in normal urothelium and bladder cancer tissue within the hotspot regions. A combination of measured hotspot burden and personal risk factors was used to fit machine learning classification models. The efficacy of each model to differentiate between adjacent benign urothelium from bladder cancer patients and normal urothelium from healthy donors was measured. A random forest model using a combination of personal risk factors and mutations within MIBC hotspots yielded the highest AUC of 0.9286 for the prediction of high- vs. low-risk normal urothelium. Currently, there are no effective biomarkers to assess subclinical field disease and early carcinogenic progression in the bladder. Our findings demonstrate novel differences in mutation hotspots in NMIBC and MIBC and provide the first evidence for mutation hotspots to aid in the assessment of cancer risk in the normal urothelium. Early risk assessment and identification of patients at high risk of bladder cancer before the clinical presentation of the disease can pave the way for targeted personalized preventative therapy.

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Section: Discussionmentioning

confidence: 99%