Human papillomavirus in HIV associated lung cancers

HIV相关肺癌中的人乳头瘤病毒

• 批准号: 10361530
• 负责人: Zhen Lin
• 金额: $ 35.24万
• 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/10361530
• 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.

总结 近年来，由于HAART治疗，艾滋病定义癌症的发病率急剧下降。 相比之下，非艾滋病定义的癌症（NADC），特别是肺癌（LC）的发病率上升了2.5%。 超过3倍。在美国，LC已成为最常见的NADC，发病率为204例/ 十万人年LC也是NADC最常见的死亡原因，占癌症的21%- 艾滋病毒（+）感染者的死亡率。虽然吸烟是HIV相关LC的一个关键风险因素，但HIV（+） 在控制吸烟状况后，个体的LC风险仍增加3倍，表明其他因素 是导致发病率上升的原因与其他常见的艾滋病毒相关癌症（如宫颈癌）不同， 癌症、非霍奇金淋巴瘤和卡波西肉瘤，HIV相关LC没有已知的病毒 病因学为了发现HIV相关LC的任何潜在肿瘤病原体，我们利用了我们的Next- 基于代测序的PARSES管道可询问1，000多个LC RNA-seq数据集。我们 发现人乳头瘤病毒（HPV）与HIV（+）人群中的LC存在因果关系。的 该提案的总体目标是使用我们的良好- 已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检验HPV和LC之间存在因果关系的假设 在HIV（+）人群中，但在一般人群中没有。此外，我们还将检验HPV 通过增强雌激素介导的生长信号和表达病毒来促进肺癌发生 HIV（+）个体中E5/E6/E7/hpv-circ-880-408癌基因。我们将阐明HPV的关键作用， 癌基因产物，包括一种新的病毒环状RNA和雌激素介导的生长信号和免疫- HIV相关肺癌发生中的逃避。我们将同时考察存在的一个重要概念 能够用抗雌激素和/或抗HPV方案精确治疗HPV（+）HIV相关LC， 个性化医疗此外，通过确定HPV病因，我们的工作可能有助于通过促进 HPV疫苗对男女都适用。总之，研究的完成将在概念上增加我们的 了解HIV相关LC，并提供潜在的独特治疗机会， 使HIV（+）LC患者亚组受益。