MicroRNA-Based Cancer Mortality Risk Scoring System and hTERT Expression in Early-Stage Oral Squamous Cell Carcinoma

Abstract

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 <0) mortality risk categories. For the high-risk group, surgery with neck dissection significantly improved the 5-year survival to 75% from 46% with surgery only ( 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.

Building consensus on the application of organoid-based drug sensitivity testing in cancer precision medicine and drug development

“…3) Patients considering targeted therapies 32 , 109 , 110 . Organoid DST can help predict the response to targeted treatments for patients with specific genetic mutations or alterations.…”

“…4) Patients with rare or hard-to-treat cancers 110 . Organoid DST can help identify potential targeted therapies or novel drug combinations that may be more effective for rare or hard-to-treat cancer types.…”

“…3) Targeted therapy 32 , 109 , 110 . Targeted therapy is underutilized in most solid tumors, excluding lung and breast malignancies, for which targeted therapy is relatively well-established.…”

“…This information can guide treatment decisions and prevent unnecessary exposure to ineffective drugs. [110]. Organoid DST can help identify potential targeted therapies or novel drug combinations that may be more effective for rare or hard-to-treat cancer types.…”

Meme Kanseri Hastalarında hTERT Gen Ekspresyonunun Klinikopatolojik Önemi

“…Yüksek hTERT ekspresyonunun, mide, akciğer, servikal, baş ve boyun, meme ve yumurtalık kanseri ve glioblastoma gibi solid (katı) tümörlerde kötü prognoz ile ilişkili olduğu rapor edilmiştir (8,9). hTERT'in aşırı ekspresyonu, daha kısa medyan tekrarlama süresi ve ölümle ilişkilidir ve bu da onu umut verici bir ilaç hedefi haline getirmektedir (10)…”