MicroRNA-Based Cancer Mortality Risk Scoring System and hTERT Expression in Early-Stage Oral Squamous Cell Carcinoma
| Autor: | Masataka Shimonosono, Brenda Y. Hernandez, Richard D. Carvajal, Austin J. Shackelford, Tian Wang, Carleigh R. Canterbury, Claire R. Stewart, Regina M. Santella, Fatemeh Momen-Heravi, Shuang Wang, Matt Levin, David I. Kutler, Angela J. Yoon, Hiroshi Nakagawa, Zohreh AkhavanAghdam, Scott Troob, Elizabeth Philipone, Scott M. Peters, Bradley D. McDowell |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Oncology medicine.medical_specialty Article Subject medicine.medical_treatment TNM staging system 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Stage (cooking) RC254-282 Framingham Risk Score Proportional hazards model business.industry Hazard ratio Cancer Neoplasms. Tumors. Oncology. Including cancer and carcinogens Neck dissection medicine.disease 030104 developmental biology 030220 oncology & carcinogenesis Cancer vaccine business Research Article |
| Zdroj: | Journal of Oncology Journal of Oncology, Vol 2021 (2021) |
| ISSN: | 1687-8450 |
| Popis: | We have previously constructed a novel microRNA (miRNA)-based prognostic model and cancer-specific mortality risk score formula to predict survival outcome in oral squamous cell carcinoma (OSCC) patients who are already categorized into “early-stage” by the TNM staging system. A total of 836 early-stage OSCC patients were assigned the mortality risk scores. We evaluated the efficacy of various treatment regimens in terms of survival benefit compared to surgery only in patients stratified into high (risk score ≥0) versus low (risk score p < 0.001 ); a Cox proportional hazard model on time-to-death demonstrated a hazard ratio of 0.37 for surgery with neck dissection (95% CI: 0.2–0.6; p = 0.0005 ). For the low-risk group, surgery only was the treatment of choice associated with 5-year survival benefit. Regardless of treatment selected, those with risk score ≥2 may benefit from additional therapy to prevent cancer relapse. We also identified hTERT (human telomerase reverse transcriptase) as a gene target common to the prognostic miRNAs. There was 22-fold increase in the hTERT expression level in patients with risk score ≥2 compared to healthy controls ( p < 0.0005 ). Overexpression of hTERT was also observed in the patient-derived OSCC organoid compared to that of normal organoid. The DNA cancer vaccine that targets hTERT-expressing cells currently undergoing rigorous clinical evaluation for other tumors can be repurposed to prevent cancer recurrence in these high-risk early-stage oral cancer patients. |
| Databáze: | OpenAIRE |
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