Background: Metabolic disorders and chronic liver disease (CLD) play crucial roles in the development and progression of liver cancer (LC). Since the ethnic minority population increasingly suffers from CLD and LC, it is vital to understand the biosocial factors contributing to CLD and LC. The ’All of Us’ database, with significant participation from minority populations, provides a valuable tool for studies in different racial/ethnic groups. Using different databases, including the ‘All of Us’ and ‘The Cancer Genome Atlas’, this study aimed to understand the biosocial factors contributing to CLD and LC. Methods: Using ‘All of Us’ data, confounding factors like the lack of immunization, comorbidities, and socioeconomic status (SES) barriers were analyzed in a cohort of 33767 CLD [non-alcoholic fatty liver disease, alcoholic liver disease, and Hepatitis B and C] patients. Among the 556 LC patients in the ‘All of Us’ database, 92% had CLD. Since hypoxanthine is known to be increased in the urine of LC patients, purine metabolic pathway genes were analyzed using different databases and validated using publicly available RNASeq data. Results: We identified several confounding factors associated with CLD in Hispanic (HA) and African American (AA) populations compared to the non-Hispanic White (NHW) populations. HA and AA CLD patients suffer from high SES barriers. While most of the genes related to the purine metabolic pathway were upregulated in LC, xanthine dehydrogenase (XDH), which converts hypoxanthine to uric acid, showed a downregulation in the tumor compared to the normal tissues. The TCGA data among different racial/ethnic groups showed that only in Asian (AN) LC tumors the XDH expression was significantly lower compared to the NHW. The decreased XDH mRNA expression in AN LC compared to benign tissues was further validated using publicly available RNAseq datasets. Survival analysis confirmed poor overall survival among the AN LC patients with lower XDH expression in their tumors. Conclusions: Our study identified several confounding factors contributing to the minority CLD population. This study also identified decreased XDH expression as a critical metabolic alteration that has clinical significance in AN LC patients.
背景：代谢紊乱与慢性肝病（CLD）在肝癌（LC）的发生与发展中扮演着关键角色。鉴于少数民族群体日益受到CLD与LC的困扰，理解导致CLD与LC的生物社会因素至关重要。"All of Us"数据库因有大量少数民族人群参与，为不同种族/族裔群体的研究提供了宝贵工具。本研究利用包括"All of Us"和"癌症基因组图谱"在内的多个数据库，旨在探究导致CLD与LC的生物社会因素。 方法：基于"All of Us"数据，我们对33767例CLD患者（包括非酒精性脂肪肝病、酒精性肝病以及乙型与丙型肝炎）队列中，诸如免疫接种缺失、合并症及社会经济地位障碍等混杂因素进行了分析。在"All of Us"数据库的556例LC患者中，92%伴有CLD。鉴于已知LC患者尿液中次黄嘌呤水平升高，我们利用不同数据库分析了嘌呤代谢通路基因，并通过公开可用的RNA测序数据进行了验证。 结果：与非西班牙裔白人（NHW）群体相比，我们识别出西班牙裔（HA）和非裔美国人（AA）CLD患者相关的若干混杂因素。HA与AA的CLD患者面临较高的社会经济地位障碍。虽然多数嘌呤代谢通路相关基因在LC中表达上调，但将次黄嘌呤转化为尿酸的黄嘌呤脱氢酶（XDH）在肿瘤组织中的表达较正常组织下调。对不同种族/族裔群体的TCGA数据分析显示，仅在亚洲（AN）LC肿瘤中，XDH表达显著低于NHW群体。利用公开RNA测序数据集进一步验证了AN的LC组织中XDH mRNA表达较良性组织降低。生存分析证实，肿瘤中XDH表达较低的AN的LC患者总生存期较差。 结论：本研究识别了导致少数民族CLD人群患病的若干混杂因素，同时发现XDH表达降低是AN的LC患者中具有临床意义的关键代谢改变。
Biosocial Determinants of Health Among Patients with Chronic Liver Disease and Liver Cancer
肿瘤(癌症)患者之家