上尿路尿路上皮癌(upper urinary tract urothelial carcinoma，UTUC)的生物学特性和预后存在异质性，术后容易出现复发。课题组前期通过大样本的临床研究发现：中国人群UTUC患者的临床病理特征与西方人群明显不同：女性患者比例高、病理级别低、复发率高等。这可能与中国人群广泛服用含有马兜铃酸（Aristolochic acid，AA）的中草药有关。因此，本课题将主要研究女性UTUC患者的分子病理分型、复发的分子机制以及致癌的关键基因和驱动基因；并比较分析AA相关性UTUC和非AA相关性UTUC的异同，建立临床预后模型，以指导临床诊断治疗、估评预后危险因素、提高患者生存率。

Upper urinary tract urothelial carcinoma (UTUC) is a rare and heterogonous disease. The multifocality and incidence of bladder recurrence is much higher in UTUC, which is associated with surgery complications, higher costs of treatment, and potential further radical cystectomy. However, none of the molecular markers has fulfilled the clinical and statistical criteria necessary to support their introduction in daily clinical decision making. Our previous studies had shown that a higher incidence of UTUC has also been described in Chinese patients compared to the western patients. Preliminary data indicates that arsenic exposure promotes UTUC tumorigenesis. It has been shown that AA will form DNA adduct (AL-DNA) which leads to unique genetic mutations, A to T. Due to the broadly consumption of Chinese herbs which contain aristolochic acid (AA) in Chinese patients. We hypothesize that arsenic exposure may contribute the unique clinical features in Chinese patients. To prove it, we will detect genomic variants by whole genome sequencing. By comparing the AA-associated UTUC (AA-UTUC) with non-AA-associated UTUC (NAA-UTUC), we will systematically elucidate the molecular subtypes and mechanisms of Chinese UTUC tumorigenesis and recurrence. Then, we will integrate functional analysis and network analysis to identify the critical genetic variations which promote the tumor initiation and recurrence. Taken together, our study will facilitate the establishment of clinical prediction models which might help to guide decision-making with regard to timing of surveillance and type of treatment strategies.