(Dallas—March 10, 2022, 5:11 p.m.) — While the incidence level of most cancers has declined over the last decade, anal squamous cell cancer (ASCC), an HPV-associated malignancy, is one of few cancers in the US that is increasing in incidence. However, findings presented at the Society of Surgical Oncology 2022 International Conference on Surgical Care provide a framework for further characterize expressed genes that may serve as biomarkers to identify those lesions most likely to progress to anal squamous cell cancer.
Pathogenesis of ASCC is well described with progression from normal mucosa through stages of anal intraepithelial neoplasia (AIN) and is thought to be driven by the Human Papillomavirus E6 and E7 viral oncogenes. As most anal intraepithelial neoplasia does not progress to anal squamous cell cancer, biomarkers to identify high-risk AIN3 requiring intervention would be valuable, according to Leah E. Hendrick, MD, MS UTHSC Department of Surgery, who presented the study’s findings.
Using next generation RNA sequencing (RNA-Seq), we sought to identify patterns of differential gene expression across the spectrum of anal squamous cell cancer progression with the goal of identifying potential biomarkers for selective management of AIN3.
Dr. Hendrick analyzed 40 formalin-fixed paraffin embedded samples [14 ASCC, 17 AIN3, 9 normal mucosa and histological diagnoses were confirmed, tissues microdissected, and RNA was extracted and purified. The researchers then employed multi-step bioinformatics methodology to generate principal component analysis models, model differential expression of genes between normal, AIN3 and tumor samples via Partial Least Squares and volcano plots and, identify pathways most commonly affected by differential expression across ASCC development.
As expected, PCA demonstrated clear 2-dimensional separation between the normal mucosa and anal squamous cell cancer specimens. Gene expression in AIN3 trended toward that of normal mucosa samples. Significant differential expression was noted between NM, AIN3, and ASCC by volcano plot analysis. Of 1126 selected genes, 118 probes were significant for differential expression between AIN3 and ASCC with 50 discrete genes clustering AIN3 to ASCC.
“We have demonstrated clear differential gene expression between normal mucosa, of anal intraepithelial neoplasia, and anal squamous cell cancer,” Dr. Hendrick reporter. “Furthermore, from a large panel of probes, we have identified a small subset of genes with discrete shared expression between some of anal intraepithelial neoplasia and anal squamous cell cancer.”
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The Society of Surgical Oncology is a dynamic global community of cancer surgeons shaping advancements in the profession to deliver the highest quality surgical care for cancer patients. SSO promotes leading-edge research, quality standards and knowledge exchange, connecting cancer surgeons worldwide to continuously improve cancer outcomes. Our highly regarded educational resources, the Society’s clinical journal, Annals of Surgical Oncology and events, including SSO 2022 – International Conference on Surgical Cancer Care, inspire members and spur each cancer surgeon to grow, improve and thrive.