scholarly journals Plasma-Derived Exosomal microRNA-130a Serves as a Noninvasive Biomarker for Diagnosis and Prognosis of Oral Squamous Cell Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Tao He ◽  
Xiangyu Guo ◽  
Xue Li ◽  
Chunjuan Liao ◽  
Xiaorong Wang ◽  
...  

Exosomal microRNAs (miRNAs) are considered as potential stable biomarkers in many types of human cancer, but investigations of plasma-derived exosomal miRNAs in oral squamous cell carcinoma (OSCC) are still lacking. The aim of this study is to evaluate the diagnostic and prognostic values of exosomal miR-130a in OSCC patients. Exosomes were isolated from plasma samples which were collected from 184 OSCC patients before surgery and 196 healthy individuals. Primary OSCC and paired adjacent noncancerous tissues were also obtained from 47 OSCC patients. The expression levels of miR-130a were analyzed by quantitative real-time PCR (qRT-PCR). Our results showed that the expression levels of exosomal miR-130a were significantly higher in OSCC patients than those of the healthy controls ( p < 0.0001 ). Also, the expression of miR-130a was also significantly upregulated in OSCC tissues compared with paired adjacent noncancerous tissues ( p < 0.0001 ). A significant positive correlation was found between exosomal miR-130a and tissue miR-130a levels. Receiver operating characteristic (ROC) analyses yielded an AUC value of 0.812 in discriminating OSCC patients from healthy controls. Furthermore, high levels of exosomal miR-130a were associated with the late T-stage ( p = 0.024 ), advanced TNM stage ( p = 0.003 ), and poorly differentiated OSCC ( p = 0.013 ). Patients with high exosomal miR-130a expression had significantly worse 3-year overall survival (OS) and recurrence-free survival (RFS). Multivariate analysis indicated that exosomal miR-130a was an independent prognostic factor for OS ( p = 0.001 ) and RFS ( p = 0.003 ). Our results suggest that exosomal miR-130a may serve as a promising diagnostic and prognostic biomarker for OSCC patients.

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Shuai Sun ◽  
Bowen Li ◽  
Yufan Wang ◽  
Xiang Li ◽  
Panpan Wang ◽  
...  

Background. Circular RNAs (circRNAs) are a type of covalently closed loop structure of endogenous RNAs. Recent studies have shown that circular RNAs may play an important role in human cancer. However, there is limited information on the function of circRNA in oral squamous cell carcinoma (OSCC). Methods. Hsa_circ_001242 expression levels in 40 paired OSCC tissues and four OSCC cell lines were selected using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). A receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of hsa_circ_001242 in OSCC. Results. Hsa_circ_001242 was significantly downregulated in OSCC tissues compared to paired adjacent normal tissues (P<0.001). Hsa_circ_001242 expression levels were significantly downregulated in four OSCC cell lines (SCC-9, SCC-15, SCC25, and CAL-27) than in human normal oral keratinocyte (HOK) cell lines. Moreover, the expression level of hsa_circ_001242 was negatively correlated with tumor size and T stage (P<0.05). The area under the ROC curve was 0.784. Conclusion. This study showed that hsa_circ_001242 was significantly downregulated in OSCC and may act as a potential novel biomarker for the diagnosis and treatment of OSCC.


PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6732 ◽  
Author(s):  
Chung-Ji Liu ◽  
Jen-Hao Chen ◽  
Shih-Min Hsia ◽  
Chiu-Chu Liao ◽  
Hui-Wen Chang ◽  
...  

Background The X-linked tumor suppressor gene LDOC1 is reported to be involved in oral cancer. The detection of biomarkers in salivary RNA is a non-invasive strategy for diagnosing many diseases. The aim of the present study was to investigate the potential of salivary LDOC1 as a biomarker of oral cancer. Methods We determined the expression levels of LDOC1 in the saliva of oral squamous cell carcinoma (OSCC) subjects, and investigated its correlation with various clinicopathological characteristics. The expression levels of salivary LDOC1 were detected in 53 OSCC subjects and 43 healthy controls using quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis. We used Fisher’s exact test to analyze the correlations between expression levels and clinicopathological characteristics. Results Salivary LDOC1 was significantly upregulated in females with OSCC (p = 0.0072), and significantly downregulated in males with OSCC (p = 0.0206). Eighty-nine percent of male OSCC subjects who smoked expressed low levels of LDOC1. OSCC cell lines derived from male OSCC subjects expressed low levels of LDOC1. Conclusions A high level of salivary LDOC1 expression is a biomarker of OSCC in females. A high percentage of male OSCC subjects who smoke express low levels of salivary LDOC1. A low level of salivary LDOC1 expression is a biomarker of OSCC in males.


2016 ◽  
Vol 113 (41) ◽  
pp. 11549-11554 ◽  
Author(s):  
Jau-Song Yu ◽  
Yi-Ting Chen ◽  
Wei-Fan Chiang ◽  
Yung-Chin Hsiao ◽  
Lichieh Julie Chu ◽  
...  

Most cases of oral squamous cell carcinoma (OSCC) develop from visible oral potentially malignant disorders (OPMDs). The latter exhibit heterogeneous subtypes with different transformation potentials, complicating the early detection of OSCC during routine visual oral cancer screenings. To develop clinically applicable biomarkers, we collected saliva samples from 96 healthy controls, 103 low-risk OPMDs, 130 high-risk OPMDs, and 131 OSCC subjects. These individuals were enrolled in Taiwan’s Oral Cancer Screening Program. We identified 302 protein biomarkers reported in the literature and/or through in-house studies and prioritized 49 proteins for quantification in the saliva samples using multiple reaction monitoring-MS. Twenty-eight proteins were successfully quantified with high confidence. The quantification data from non-OSCC subjects (healthy controls + low-risk OPMDs) and OSCC subjects in the training set were subjected to classification and regression tree analyses, through which we generated a four-protein panel consisting of MMP1, KNG1, ANXA2, and HSPA5. A risk-score scheme was established, and the panel showed high sensitivity (87.5%) and specificity (80.5%) in the test set to distinguish OSCC samples from non-OSCC samples. The risk score >0.4 detected 84% (42/50) of the stage I OSCCs and a significant portion (42%) of the high-risk OPMDs. Moreover, among 88 high-risk OPMD patients with available follow-up results, 18 developed OSCC within 5 y; of them, 77.8% (14/18) had risk scores >0.4. Our four-protein panel may therefore offer a clinically effective tool for detecting OSCC and monitoring high-risk OPMDs through a readily available biofluid.


2018 ◽  
Vol 47 (6) ◽  
pp. 2511-2521 ◽  
Author(s):  
Si-Yu Zhao ◽  
Jun Wang ◽  
Shao-Bo Ouyang ◽  
Zi-Kun Huang ◽  
Lan Liao

Background/Aims: Recent studies have demonstrated that circular RNAs (circRNAs) can serve as potential molecular markers for disease diagnosis. However, little is known about their diagnostic potential for oral squamous cell carcinoma (OSCC). This study aimed to determine the expression of circRNAs in the saliva of OSCC patients to identify novel biomarkers for OSCC screening. Methods: Microarray screening of circRNA was performed to identify differentially expressed circRNAs in saliva from 3 OSCC patients compared with 3 healthy controls. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to validate the results, and the association between these confirmed salivary circRNAs and clinicopathological features was analyzed using the chi-squared test. A receiver operating characteristic (ROC) curve was constructed to evaluate the diagnostic value of the circRNAs identified. Preoperative expression and postoperative expression (1 month after the surgery) of hsa_circ_0001874 and hsa_circ_0001971 was also determined. Results: Our results indicated 12 upregulated and 20 downregulated circRNAs in the saliva from the OSCC patients compared with that from the healthy controls. Among the differentially expressed circRNAs, hsa_circ_0001874, hsa_circ_0001971, and hsa_circ_0008068 were upregulated and hsa_circ_0000140, hsa_circ_0002632, and hsa_circ_0008792 were downregulated in the OSCC group versus the healthy group. Clinical data indicated that salivary hsa_circ_0001874 was correlated with TNM stage (P=0.006) and tumor grade (P=0.023) and that hsa_circ_0001971 was correlated with TNM stage (P=0.019). The combination of hsa_circ_0001874 and hsa_circ_0001971 showed an area under the ROC curve of 0.922 (95% confidence interval, 0.883-0.961; P< 0.001). The risk score based on the combination of hsa_circ_0001874 and hsa_circ_0001971 also discriminated patients with OSCC from patients with oral leukoplakia (P< 0.001). Moreover, the expression levels of salivary hsa_circ_0001874 and hsa_circ_0001971 were clearly decreased in the postoperative samples compared with preoperative samples (P< 0.001). Conclusions: This is the first study to demonstrate the potential of salivary hsa_circ_0001874 and hsa_circ_0001971 as biomarkers for the diagnosis of OSCC.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e17527-e17527
Author(s):  
Vijay Kumar Srinivasalu ◽  
Narayana Subramaniam ◽  
Subramania Iyer ◽  
Ajit Nambiar ◽  
Manzoor Koyakutty ◽  
...  

e17527 Background: PDL-1 expression has been shown in multiple tumours to be a key factor in treatment response and immunogenicity. In oral squamous cell carcinoma (OSCC), its role is controversial; the expression levels, prognostic significance and therapeutic relevance are unclear. This study was performed to determine the incidence of PDL-1 expression in OSCC, and to determine its correlation with demographic, clinical and pathological features, recurrence and survival. Methods: PDL-1 IHC (Dako kit) was determined on 64 samples of OSCC obtained during curative intent resection. PDL-1 expression levels were determined in tumour (T) and tumour infiltrating lymphocytes (TILs). Statistical analysis was performed. Results were validated on the mRNA-seq data from the Cancer Genome Atlas (TCGA) for head and neck squamous cell carcinoma (HNSCC). Results: 64 patients were included in the final analysis with a mean age of 54 years. < 1% expression was the most common for T (92%) and TILs (56%). Tumour PDL-1 expression < 1% had higher risk of lymphovascular invasion (LVI) (p = 0.044) and bone invasion (p = 0.010). TIL PDL-1 expression < 1% was more common in patients ≤45 years (p = 0.023) with higher chances of local recurrence (p = 0.020) and reduced local recurrence free survival (p = 0.047). For the TCGA data, low ( < 1%) PDL-1 expression was associated with a significant reduction in OS and DFS in the young (≤45 years) (p = 0.0078 and 0.0089 respectively), but not for older patients ( > 45 years) (p = 0.21 and 0.88 respectively). Conclusions: PDL-1 expression in OSCC was low. TIL PDL-1 expression < 1% was more common in those ≤45 years, and associated with a higher chance of local recurrence and poorer survival. The role of PDL-1 expression in prognosis of OSCC is controversial, with our data being the first to correlate low PDL-1 expression and poorer outcomes with younger patients. These results were validated by the TCGA data for HNSCC across multiple subsites. Further study is required to determine if this pathway plays a significant role in local control and survival.


2019 ◽  
Vol 20 (17) ◽  
pp. 4222 ◽  
Author(s):  
Alejandro I. Lorenzo-Pouso ◽  
Mario Pérez-Sayáns ◽  
Samuel Rodríguez-Zorrilla ◽  
Cintia Chamorro-Petronacci ◽  
Abel García-García

Cancer cells overexpress proton exchangers at the plasma membrane in order acidify the extracellular matrix and maintain the optimal pH for sustaining cancer growth. Among the families of proton exchangers implicated in carcinogenesis, carbonic anhydrases (CAs), monocarboxylate transporters (MCTs), Na+/H+ exchangers (NHEs), sodium bicarbonate cotransporters (NBCs), and vacuolar ATPases (V-ATPases) are highlighted. Considerable research has been carried out into the utility of the understanding of these machineries in the diagnosis and prognosis of several solid tumors. In addition, as therapeutic targets, the interference of their functions has contributed to the discovery or optimization of cancer therapies. According to recent reports, the study of these mechanisms seems promising in the particular case of oral squamous cell carcinoma (OSCC). In the present review, the latest advances in these fields are summarized, in particular, the usefulness of proton exchangers as potential prognostic biomarkers and therapeutic targets in OSCC.


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