Maroney Kevin J, Ye Yuanfan, Sudenga Staci L, Diffalha Sameer Al, Banerjee Nilam Sanjib, Shrestha Sadeep, Bansal Anju
Department of Medicine, Division of Infectious Diseases, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Ob/gyn-Maternal and Fetal Medicine, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
J Med Virol. 2025 May;97(5):e70371. doi: 10.1002/jmv.70371.
Squamous cell carcinoma of the anus (SCCA) or anal cancer (AC) is an understudied cancer with a high occurrence rate in people with HIV (PWH), especially men having sex with men (MSM). Furthermore, AC recurs in approximately one-fourth of patients who undergo standard care with chemoradiation therapy (CRT). Using bulk RNA sequencing data of AC obtained from 12 patients with non-recurrent (NR, N = 9) or recurrent (R, N = 3) cancer, we previously showed upregulated expression of key immune genes in the NR compared to the R group. Although the main causative agent of AC is high-risk human papillomavirus (HPV), association of host and viral RNA transcript expression contributing to AC recurrence has not been extensively studied. The objective of the current study was to determine whether enrichment of specific HPV genotypes and/or HPV gene expression patterns differentiate the two groups and if any specific viral (HPV) and host (human) immune mediators correlate with each other. Using bulk RNA sequencing data and VIRTUS 2, we detected viral RNA reads mapping to seven high-risk and six low-risk HPV types, of which the high-risk HPV16 observed in 83% (10/12) AC tumors (7/9 NR and 3/3 R). Rate of all HPV genomes trended toward a decrease in NR AC isolates and correlation between HPV types was more commonly observed in low-risk ones. Analysis of HPV 16 gene expression profile showed a significantly lower positivity rate for a polycistronic transcript encoding for E7^L1 in the NR group (1/9, NR vs. 3/3, R, p < 0.05). An unbiased correlation analysis of HPV-human transcript expression showed a direct correlation between HPV transcripts and human genes involved in cell growth. The data also identified human transcripts showing an inverse correlation with HPV gene expression. These included genes involved in negative regulation of growth, proliferation, and immune response. Taken together, these data indicate that concurrent analyses of viral and host factors in the same tumor can identify potential new therapeutic targets to ameliorate cancer recurrence post-treatment.
肛门鳞状细胞癌（SCCA）或肛管癌（AC）是一种研究较少的癌症，在艾滋病毒感染者（PWH）中发病率较高，尤其是男男性行为者（MSM）。此外，约四分之一接受标准放化疗（CRT）的肛管癌患者会复发。我们此前利用从12例非复发性（NR，N = 9）或复发性（R，N = 3）肛管癌患者获得的大量RNA测序数据，发现与复发组相比，非复发组关键免疫基因的表达上调。虽然肛管癌的主要致病因素是高危型人乳头瘤病毒（HPV），但宿主和病毒RNA转录本表达与肛管癌复发的关联尚未得到广泛研究。本研究的目的是确定特定HPV基因型的富集和/或HPV基因表达模式是否能区分这两组患者，以及是否有任何特定的病毒（HPV）和宿主（人类）免疫介质相互关联。利用大量RNA测序数据和VIRTUS 2，我们检测到映射到7种高危型和6种低危型HPV类型的病毒RNA读数，其中83%（10/12）的肛管癌肿瘤中观察到高危型HPV16（7/9 NR和3/3 R）。所有HPV基因组的比例在非复发肛管癌分离株中呈下降趋势，且HPV类型之间的相关性在低危型中更常见。对HPV 16基因表达谱的分析显示，非复发组中编码E7^L1的多顺反子转录本的阳性率显著较低（1/9，NR vs. 3/3，R，p < 0.05）。对HPV - 人类转录本表达的无偏相关分析显示，HPV转录本与参与细胞生长的人类基因之间存在直接相关性。数据还鉴定出与HPV基因表达呈负相关的人类转录本。这些基因包括参与生长、增殖和免疫反应负调控的基因。综上所述，这些数据表明，对同一肿瘤中的病毒和宿主因素进行同步分析可以识别潜在的新治疗靶点，以改善治疗后癌症的复发情况。
