Abstract
This study aimed to investigate whether the progression risk score (PRS) developed from cytoplasmic immunohistochemistry (IHC) biomarkers is available and applicable for assessing risk and prognosis in oral cancer patients. Participants in this retrospective case-control study were diagnosed between 2012 and 2014 and subsequently underwent surgical intervention. The specimens from surgery were stained by IHC for 16 cytoplasmic target markers. We evaluated the results of IHC staining, clinical and pathological features, progression-free survival (PFS), and overall survival (OS) of 102 oral cancer patients using a novel estimation approach with unsupervised hierarchical clustering analysis. Patients were stratified into high-risk (52) and low-risk (50) groups, according to their PRS; a metric consisting of cytoplasmic PLK1, PhosphoMet, SGK2, and SHC1 expression. Moreover, PRS could be extended for use in the Cox proportional hazard regression model to estimate survival outcomes with associated clinical parameters. Our study findings revealed that the high-risk patients had a significantly increased risk in cancer progression compared with low-risk patients (hazard ratio (HR) = 2.20, 95% confidence interval (CI) = 1.10–2.42, p = 0.026). After considering the influences of demographics, risk behaviors, and tumor characteristics, risk estimation with PRS provided distinct PFS groups for patients with oral cancer (p = 0.017, p = 0.019, and p = 0.020). Our findings support that PRS could serve as an ideal biomarker for clinical use in risk stratification and progression assessment in oral cancer.
Highlights
A high occurrence of oral cancer recurrence and metastasis events result from this cancer’s late presentation, resulting in poor survival in patients with oral cancer [1]
There were no significant differences between the two groups in terms of age, sex, risk behaviors, primary site, grade, lymphovascular invasion (LVI), perineural invasion (PNI), margin status, extranodal extension (ENE), tumor stage [17], lymph node invasion, and pathological stage
The disease-progressed group showed a higher proportion of poor clinical characteristics, including LVI, PNI (19.4% vs. 9.1%), ENE (13.9% vs. 6.1%), tumor stage IV (33.3% vs. 12.1%), lymph node invasion (27.8% vs. 24.2%), and advanced pathological stage (50.0% vs. 34.8%)
Summary
A high occurrence of oral cancer recurrence and metastasis events result from this cancer’s late presentation, resulting in poor survival in patients with oral cancer [1]. Multidisciplinary interventions, including radical surgery, radiotherapy, and cytotoxic chemotherapy, worsen the quality of life of patients. Recent studies have started to emphasize personalized biomarker-driven therapeutic strategies to guide treatments in refractory advanced cancer, including basket trials and umbrella trials [7,8]. Some biomarker-driven treatment strategies have even moved to guide multidisciplinary interventions. Patients with high Slug expression on IHC have a higher risk of radio- and chemotherapy resistance, and earlier surgery resulted in better survival than either definitive radiotherapy or chemoradiotherapy [9]. There is still a lack of standard guidelines for biomarkers of IHC expression or genetic alterations to predict the treatment response or prognosis in oral cancer
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