scholarly journals Aberrant Expression of PTPN-14 and Wilms’ Tumor 1 as Putative Biomarker for Locoregional Recurrence in Oral Squamous Cell Carcinoma

Author(s):  
Seema Nayak ◽  
Madan Lal Brahma Bhatt ◽  
Madhu Mati Goel ◽  
Seema Gupta ◽  
Divya Mehrotra ◽  
...  

Abstract Objective Locoregional recurrence in oral squamous cell carcinoma (OSCC) is a major concern that leads to metastasis. Its detection at earliest stage is very important to increase the overall survival of the patient. There is no any biomarker for locoregional recurrence in oral squamous cell carcinoma (OSCC). The aim of this study was to find a biomarker for locoregional recurrence in tissue and serum at gene and protein level. Methods This work studied the expression of protein tyrosine phosphatase nonreceptor type 14 (PTPN-14) and Wilms’ tumor 1 (WT-1) in patients and correlated their expression with locoregional recurrence and survival. Tissue expression was observed in formalin fixed tissue biopsies of 96 OSCC and 32 healthy controls by immunohistochemistry using antibody against PTPN-14 and WT-1 and serum level was estimated by enzyme-linked immunosorbent assay in pre- and post-chemoradiotherapy samples. mRNA expression was determined by using real-time polymerase chain reaction. Patients were followed for 3 years for locoregional recurrence. Results Expression of PTPN-14 and WT-1 in OSCC was upregulated (aberrant) in tissue and sera in both gene and protein level as compared with healthy controls. Locoregional recurrence was observed in 10 (23.80%) patients and significantly associated with PTPN-14 (p < 0.047) and WT-1 expression (p < 0.031). Conclusion PTPN-14 and WT-1 may be used as biomarker to identify patients for higher risk of locoregional recurrence. This study drove molecular aspect and phenotypic level to derive new emergent strategies in future for recurrent OSCC.

2012 ◽  
Vol 42 (2) ◽  
pp. 133-139 ◽  
Author(s):  
Toshinari Mikami ◽  
Tomohiro Hada ◽  
Naoyuki Chosa ◽  
Akira Ishisaki ◽  
Harumi Mizuki ◽  
...  

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.


2020 ◽  
Vol 29 (4) ◽  
pp. 543-552
Author(s):  
Akhilesh Krishna ◽  
Vineeta Singh ◽  
Shraddha Singh ◽  
Sachil Kumar ◽  
Vijay Kumar ◽  
...  

BACKGROUND: Histone deacetylases (HDACs) are considered as an essential regulator of cellular proliferation, differentiation, and apoptosis. The HDAC2 enzyme of Class I HDACs plays an important role in tumor progression of human malignancies. OBJECTIVE: The aim of the present study was to analyze the HDAC2 gene expression in pre-oral cancer and oral squamous cell carcinoma (OSCC), and its association with clinico-pathological features. METHODS: The HDAC2 protein expression was analyzed through the immunohistochemistry and western blot techniques in 82 oral pre-malignant, 90 OSCC, and 16 normal control tissues. qRT-PCR was used to quantify the mRNA fold change in all groups. RESULTS: The HDAC2 protein and mRNA levels were significantly higher in OSCC and pre-oral cancer groups compared to the controls. Immunostaining of HDAC2 protein was enhanced in 84.4% of OSCC and 67.1% of pre-cancerous tissue sections (p< 0.01). The mean protein level was analyzed as 1.96 ± 0.44 in oral carcinoma, 1.61 ± 0.39 in pre-cancer and 0.96 ± 0.10 in control tissues. In addition, HDAC2 mean protein level was associated with histological differentiation (OR = 25, p< 0.05) and tumor-node-metastasis (TNM) stages (OR = 6.2, p< 0.05) of OSCC patients. CONCLUSIONS: The upregulated HDAC2 gene in pre-cancer and OSCC tissues indicates its crucial role in the transformation of pre-malignant to malignant carcinoma. It could be a potential cancer biomarker of prognosis and targeted therapy in OSCC.


2017 ◽  
Vol 21 (2) ◽  
pp. 81-85 ◽  
Author(s):  
Kiran Agarwal ◽  
Anju Chauhan ◽  
Jitender Prasad ◽  
Pravesh Mehra ◽  
Shilpa Kumar ◽  
...  

ABSTRACT Introduction Oral squamous cell carcinoma (OSCC) is a major health problem in Southeast Asia, including India. Areca nut chewing is a major health hazard in India, which has been implicated in the etiology of OSCC. Hypoxia-inducible factor-1 (HIF-1) is a major transcription factor involved in adaptation under hypoxic condition, a common finding in solid tumors. The present study was conducted to evaluate the effect of different habits including areca nut chewing on HIF-1 expression in patients with OSCC. Materials and methods It was a hospital-based observational case-control study. The study comprised 50 histologically proven cases of OSCC and 50 healthy controls. The HIF-1α level was measured by commercially available enzyme-linked immunosorbent assay (ELISA) in the blood samples. The data were analyzed using Statistical Package for the Social Sciences (SPSS) software version 20. Results The HIF-1α levels were found significantly higher in the patients with areca nut consumption in addition to other addictive habits. Isolated influence could not be discerned as there was only one patient who gave history of only areca nut chewing. Conclusion Our findings prove that HIF-1α expression is upregulated by areca nut chewing, which leads to worse prognosis. This calls for widespread awareness programs regarding the deleterious effects of areca nut chewing among the general population. How to cite this article Prasad J, Goswami B, Agarwal K, Mehra P, Kumar S, Pahuja BK, Chauhan A, Ahirwar AK. Effect of Areca Nut Consumption on Hypoxia-inducible Factor-1 Alfa Expression in Patients with Oral Squamous Cell Carcinoma. Indian J Med Biochem 2017;21(2):81-85.


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