MicroRNA-Based Cancer Mortality Risk Scoring System and hTERT Expression in Early-Stage Oral Squamous Cell Carcinoma.
MicroRNA-Based Cancer Mortality Risk Scoring System and hTERT Expression in Early-Stage Oral Squamous Cell Carcinoma.
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DOI：
10.1155/2021/8292453
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发表时间：
2021
影响因子：
--
通讯作者：
Nakagawa H
中科院分区：
文献类型：
--
作者：
Yoon AJ;Santella RM;Wang S;Kutler DI;Carvajal RD;Philipone E;Wang T;Peters SM;Stewart CR;Momen-Heravi F;Troob S;Levin M;AkhavanAghdam Z;Shackelford AJ;Canterbury CR;Shimonosono M;Hernandez BY;McDowell BD;Nakagawa H
我们之前构建了一个新的基于microRNA （miRNA）的预后模型和癌症特异性死亡风险评分公式，用于预测口腔鳞状细胞癌（OSCC）患者的生存结果，这些患者已经被TNM分期系统划分为“早期”。对836例早期OSCC患者进行死亡风险评分。我们将患者分为高（风险评分≥0）和低（风险评分<0）死亡风险类别，从生存获益方面评估了各种治疗方案与仅手术的疗效。对于高危组，手术合并颈部清扫显著提高5年生存率，从仅手术组的46%提高到75% (p < 0.001)；关于死亡时间的Cox比例风险模型显示，颈部剥离手术的风险比为0.37 （95% CI: 0.2-0.6; p=0.0005）。对于低风险组，手术是与5年生存获益相关的治疗选择。无论选择何种治疗方法，风险评分≥2的患者可能受益于额外的治疗以预防癌症复发。我们还发现hTERT（人类端粒酶逆转录酶）是预后mirna共同的基因靶标。与健康对照组相比，风险评分≥2的患者hTERT表达水平升高22倍（p < 0.0005）。与正常类器官相比，患者源性OSCC类器官中也观察到hTERT的过表达。靶向htert表达细胞的DNA癌症疫苗目前正在对其他肿瘤进行严格的临床评估，可以重新用于预防这些高危早期口腔癌患者的癌症复发。
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.
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