Human papillomavirus in HIV associated lung cancers

HIV相关肺癌中的人乳头瘤病毒

• 批准号: 10253590
• 负责人: Zhen Lin
• 金额: $ 35.4万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10253590
• 关键词: AIDS related cancer; Acquired Immunodeficiency Syndrome; Affect; Attenuated; Biological Models; Cancer Etiology; Cancer Patient; Cancer cell line; Cause of Death; Cell Culture Techniques; Cells; Cessation of life; Clinical; Data Set; Development; Disease; Disease Management; Epithelial Cells; Estrogen Antagonists; Estrogen Receptor alpha; Estrogens; Etiology; Exhibits; Feedback; Future; Gene Expression; General Population; Genetic Transcription; Genomics; Goals; Growth; HIV; HPV-High Risk; Highly Active Antiretroviral Therapy; Human Cloning; Human Papilloma Virus Vaccination; Human Papillomavirus; Human papilloma virus infection; Human papillomavirus 16; Immune Evasion; Incidence; Individual; Informatics; Kaposi Sarcoma; Lung; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Malignant neoplasm of lung; Mediating; Methods; Microbe; Monitor; Non-Hodgkin' s Lymphoma; Oncogenes; Oncogenic; Oncoproteins; Patient Care; Patients; Persons; Phenotype; Population; Regimen; Research; Risk Factors; Role; Sampling; Sensitivity and Specificity; Signal Transduction; Smoking; Smoking Status; Technology; Testing; Therapeutic; Time; Transcript; Viral; Viral Oncogene; Virus Integration; Work; base; cancer risk; circular RNA; gene product; human papilloma virus oncogene; improved; knock-down; lung cancer cell; lung carcinogenesis; malignant phenotype; next generation sequencing; novel; pathogen; personalized medicine; prevent; sex; transcriptome; transcriptome sequencing; tumor; tumor-immune system interactions; tumorigenesis

SUMMARY In recent years, the incidence of AIDS-defining cancers has dramatically decreased due to the HAART therapy. In contrast, the incidence of the non-AIDS-defining cancers (NADC), especially lung cancer (LC) has risen by more than 3 fold. In the U.S., LC has become the most common NADC with an incidence rate of 204 cases per 100,000 person-years. LC is also the most common NADC cause of death and accounts for 21% of cancer- related death in the HIV(+) population. Although smoking is a key risk factor for HIV associated LCs, HIV(+) individuals still have a 3-fold increased LC risk after controlling for smoking status, indicating that other factors are responsible for this increased incidence. Unlike other common HIV associated cancers such as cervical cancer, non-Hodgkin's lymphoma, and Kaposi's sarcoma, HIV associated LCs do not have a known viral etiology. To discover any potential oncopathogen for HIV associated LCs, we have utilized our Next- Generation-Sequencing-based PARSES pipeline to interrogate more than 1,000 LC RNA-seq data sets. We discovered that human papillomavirus (HPV) is causally associated with LCs in the HIV(+) population. The overarching goal of this proposal is to determine the involvement of HPV in HIV associated LCs using our well- established sequencing based informatics approaches as well as newly created HPV(+) HIV associated LC model systems. We will first examine the hypothesis that there is a causal association between HPV and LCs in the HIV(+) population but not in the general population. In addition, we will test the hypothesis that HPV promotes lung oncogenesis by enhancing the estrogen-mediated growth signaling and expressing viral E5/E6/E7/hpv-circ-880-408 oncogenes in the HIV(+) individuals. We will elucidate the critical roles of HPV oncogene products including a novel viral circular RNA and estrogen-mediated growth signaling and immune- evasion in HIV associated lung carcinogenesis. We will simultaneously examine an important concept of being able to precisely treat HPV(+) HIV associated LCs with anti-estrogen and/or anti-HPV regimens in the era of personalized medicine. Further, by determining the HPV etiology, our work may help prevent LCs by promoting HPV vaccination for both sexes. Together, completion of the research will add conceptually to our understanding of HIV associated LCs and provide potentially unique therapeutic opportunities and ultimately benefit a subset of HIV(+) LC patients.

概括 近年来，由于HAART治疗，定义艾滋病癌症的发生率大大降低。 相比 超过3倍。在美国，LC已成为最常见的NADC，发病率为204例 100,000人年。 LC也是最常见的NADC死亡原因，占癌症的21％ 艾滋病毒（+）人群中的相关死亡。尽管吸烟是HIV相关LC的关键危险因素，但HIV（+） 控制吸烟状态后，个人仍然有3倍的LC风险，表明其他因素 负责这种发病率的增加。与其他常见的HIV相关癌症（例如宫颈）不同 癌症，非霍奇金的淋巴瘤和卡波西肉瘤，HIV相关的LCS没有已知病毒 病因。为了发现与HIV相关的LCS的任何潜在癌变，我们使用了下一个 基于生成测序的Parses管道询问超过1,000个LC RNA-Seq数据集。我们 发现人乳头瘤病毒（HPV）与HIV（+）种群中的LCS有因果关系。这 该提案的总体目标是确定HPV使用我们的良好的HPV参与HIV相关的LCS 建立的基于测序的信息学方法以及新创建的HPV（+）HIV相关LC 模型系统。我们将首先研究HPV与LCS之间存在因果关系的假设 在艾滋病毒（+）人群中，但在一般人群中不。此外，我们将测试HPV的假设 通过增强雌激素介导的生长信号传导和表达病毒来促进肺肿瘤发生 HIV（+）个体中的E5/E6/E7/HPV-CIRC-880-408癌基因。我们将阐明HPV的关键作用 癌基产品，包括一种新型的病毒循环RNA和雌激素介导的生长信号传导和免疫 艾滋病毒相关的肺癌发生中的逃避。我们将同时研究一个重要的概念 能够准确地处理抗雌激素和/或抗HPV方案的HPV（+）HIV相关的LC 个性化医学。此外，通过确定HPV病因，我们的工作可以通过促进来帮助预防LC 两性的HPV疫苗接种。研究的完成将在概念上增加我们的 了解艾滋病毒相关的LCS，并提供潜在的独特的治疗机会，并最终 受益于HIV（+）LC患者的子集。