Novel insights on oral squamous cell carcinoma management using long non-coding RNAs

Oral squamous cell carcinoma(OSCC)is one of the most prevalent forms of head and neck squamous cell carcinomas(HNSCC)with a poor overall survival rate(about 50%),particularly in cases of metastasis.RNA-based cancer biomarkers are a relatively advanced concept,and non-coding RNAs currently have shown promising roles in the detection and treatment of various malignancies.This review underlines the function of long non-coding RNAs(lncRNAs)in the OSCC and its subsequent clinical implications.LncRNAs,a class of non-coding RNAs,are larger than 200 nucleotides and resemble mRNA in numerous ways.However,unlike mRNA,lncRNA regulates multiple druggable and non-druggable signaling molecules through simultaneous interaction with DNA,RNA,proteins,or microRNAs depending on concentration and localization in cells.Upregulation of oncogenic lncRNAs and downregulation of tumor suppressor lncRNAs are evident in OSCC tissues and body fluids such as blood and saliva indicating their potential as valuable biomarkers.Targeted inhibition of candidate oncogenic lncRNAs or overexpression of tumor suppressor lncRNAs showed potential therapeutic roles in in-vivo animal models.The types of lncRNAs that are expressed differentially in OSCC tissue and bodily fluids have been systematically documented with specificity and sensitivity.This review thoroughly discusses the biological functions of such lncRNAs in OSCC cell survival,proliferation,invasion,migration,metastasis,angiogenesis,metabolism,epigenetic modification,tumor immune microenvironment,and drug resistance.Subsequently,we addressed the diagnostic and therapeutic importance of lncRNAs in OSCC pre-clinical and clinical systems,providing details on ongoing research and outlining potential future directions for advancements in this field.In essence,this review could be a valuable resource by offering comprehensive and current insights into lncRNAs in OSCC for researchers in fundamental and clinical domains.

Diagnostic value of lncRNAs as potential biomarkers for oral squamous cell carcinoma diagnosis:a meta-analysis

Objective Several studies have revealed the critical role of long non-coding RNAs(lncRNAs)as biomarkers for diagnosing oral squamous cell carcinoma(OSCC).However,the data remain inconsistent.This meta-analysis was performed to summarize the potential of lncRNAs as OSCC biomarkers.Methods We searched PubMed,Cochrane Library,Web of Science,and China National Knowledge Infrastructure databases for literature published until December 10,2020.Study quality was assessed using Quality Assessment for Studies of Diagnostic Accuracy-2,and sensitivity,specificity,and other measures regarding lncRNAs for OSCC diagnosis were pooled using bivariate meta-analysis models.Data analyses were performed using STATA 14.0.Results Overall,8 studies with 981 cases and 585 controls were included in the pooled analysis.The pooled sensitivity,specificity,positive likelihood ratio,negative likelihood ratio,diagnostic odds ratio,and area under the receiver operating characteristic curve values were as follows:0.76[95%confidence interval(CI),0.65–0.84],0.90(95%CI,0.82–0.95),7.5(95%CI,4.20–13.40),0.27(95%CI,0.18–0.39),28(95%CI,13.00–58.00),0.90(95%CI,0.87–0.93),respectively.Deeks’funnel plot asymmetry test(P=0.56)indicated no potential publication bias.Conclusion Our meta-analytical evidence suggests that lncRNAs could be employed as a potential non-invasive diagnostic tool for OSCC.

Development of a Photodynamic Diagnosis Method for Oral Squamous Cell Carcinoma Using 5-Aminolevulinic Acid and a Luminescence Plate Reader

Purpose: To establish a simple and accurate photodynamic diagnosis (PDD) method for oral squamous cell carcinoma (OSCC). Methods: OSCC cell lines HSC-2, HSC-3, HSC-4, and Sa3, and normal human oral keratinocytes (HOK) were used. First, we examined the amount of cells needed to detect differences in fluorescence intensities for PDD. OSCC cell lines were adjusted to concentrations of 1 × 104 (104), 1 × 105 (105), and 1 × 106 (106) cells/ml. The experimental groups comprised a group with 5-aminolevulinic acid (5-ALA (+)), and a group without 5-ALA (5-ALA (-)). For each OSCC cell line, 100 μl of each concentration of cells of the 5-ALA groups was seeded onto fluorescence plates, and fluorescence intensity was measured at 60-min intervals for 240 min. Results are expressed as the ratio of fluorescence intensity in 5-ALA (+) to 5-ALA (-). As cells at the concentration of 106 cells/ml provided the clearest results, fluorescence intensities of all cell lines were measured using this concentration at 20-min intervals for 700 min using the same methods. Results: The 5-ALA (+) to (-) ratio increased in a cell concentration-dependent manner at 240 min;the ratio was highest with 106 cells/ml and lowest with 104 cells/ml. With 106 cells/ml in the 5-ALA (+) group, fluorescence intensity increased in a metabolic time-dependent manner;the increase was highest in HSC-2 cells, followed by HSC-4 cells, HSC-3 cells, Sa3 cells, and HOK. Fluorescence intensity was significantly enhanced after 40 min in HSC-2, HSC-3, and HSC-4 cells, after 60 min in Sa3 cells, and after 100 min in HOK compared to the 5-ALA (-) group (P < 0.05). Moreover, fluorescence intensity was significantly increased in OSCC cell lines compared to HOK after 40 min. Conclusion: Early detection of OSCC is possible by screening only microplate reader measurements of fluorescence intensity for PDD.

Diagnostic delay in oral squamous cell carcinoma: the role of cognitive and psychological variables

This retrospective study investigated, in two cohorts of subjects living in Southern Italy and awaiting treatment for oral squamous cell carcinoma （OSCC）, the variables related to diagnostic delay ascribable to the patient, with particular reference to the cognitive and psychological ones. A total of 156 patients with OSCC （mean age： 62 years, M/F： 2.39 ： 1） were recruited at the Universities of Palermo and Naples. Risk factors related to patient delay included： sociodemographic, health-related, cognitive and psychological variables. The analysis was conducted by considering two different delay ranges： dichotomous （≤1 month vs. 〉 1 month） and polytomous （〈1 month, 1-3 months, 〉3 months） delay. Data were investigated by univariate and multivariate analyses and a Pvalue≤0.05 was considered statistically significant. For both delay measurements, the most relevant variables were： ＇Personal experience of cancer＇ （dichotomous delay： P=0.05, odds ratio （0R）=0.33, 95% confidence interval （CI）=0. 11-0.99; polytomous delay： P=0.006, Chi-square= 10.224） and ＇Unawareness＇ （dichotomous delay： P〈0.01, 0R=4.96, 95% CI--2.16-11.37; polytomous delay： P=0.087, Chi-square=4.77）. Also ＇Denial＇ （P〈0.01, 0R=6.84, 95% CI=2.31-20.24） and ＇Knowledge of cancer＇ （P=0.079, Chi-square=8.359） were found to be statistically significant both for dichotomous and for polytomous categorization of delay, respectively. The findings of this study indicated that, in the investigated cohorts, the knowledge about cancer issues is strongly linked to the patient delay. Educational interventions on the Mediterranean population are necessary in order to increase the patient awareness and to emphasize his/her key role in early diagnosis of OSCC.

Reduced delay in diagnosis of odontogenic keratocysts with malignant transformation:A case report

BACKGROUND In rare cases,odontogenic keratocysts(ODs)transform into squamous cell carcinoma.Intervals between the first attendance of a patient and the diagnosis of OD with malignant transformation vary from weeks to years.In this article,we report a case of malignancy derived from OD with a five-day delay in diagnosis.CASE SUMMARY A 54-year-old woman was referred to Tongji Hospital in Wuhan,China with complaints of moderate pain,recurrent swelling,and pus discharge around her left maxillary lateral incisor for over 10 years.Physical examination revealed a fistula at the palatine-side mucoperiosteum of the left maxillary lateral incisor and enlarged lymph node in the left neck.Cone beam computed tomography revealed a cystic lesion with massive bone destruction from the left maxillary central incisor to the left secondary maxillary premolar and local bony destruction in the left first mandibular molar.The patient was clinically diagnosed with OD.Enucleation rather than marsupialization was performed given the risk factors of long history,recent aggravated pain,and massive bony destruction.Malignant transformation of OD was confirmed by pathologists 3 d after the operation.Radical surgery was performed,and lymph node metastasis was observed.The patient was subjected to postoperative radiotherapy and synchronous chemotherapy,and no local recurrence or distant metastasis was noted at one-year follow-up.CONCLUSION Our case suggests that clinicians should be aware of the malignant transformation of OD,especially when patients present with a long history,massive cyst,chronic inflammation,recent persistent infections,aggravated pain,numbness around the cystic lesion,and lymph node enlargement.

口腔鳞状细胞癌患者患源性诊断延误相关因素的回顾性研究

目的 分析影响口腔鳞状细胞癌患源性诊断延误形成的相关因素。方法 对208例口腔鳞状细胞癌患者的性别、年龄、是否有就诊前治疗、主要就诊原因、发病部位、病变范围等因素进行多因素方差分析,探讨它们对口腔鳞状细胞癌患源性诊断延误的影响。结果 是否有就诊前治疗,就诊症状为肿物和患源性延误存在显著的正相关(P<0.05);肿瘤发病部位中,因为牙龈部位的鳞癌而来就诊的患者诊断延误时间相对要短;性别、年龄、病变范围与诊断延误没有联系。结论 患者有就诊前治疗及病变表现为肿物,能明显延长患源性延误;发病部位为牙龈的患者,诊断延误时间较短。