scholarly journals Osteopontin Involves Cisplatin Resistance and Poor Prognosis in Oral Squamous Cell Carcinoma

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Sheng-Dean Luo ◽  
Yi-Ju Chen ◽  
Chien-Ting Liu ◽  
Kun-Ming Rau ◽  
Yi-Ching Chen ◽  
...  

Background.Osteopontin (OPN) is a multifunctional cytokine involved in cell survival, migration, and adhesion. However, its role in chemosensitivity in locally advanced oral squamous cell carcinoma (OSCC) in humans has not yet been investigated.Methods.We enrolled 121 patients with locally advanced stage IVA/B OSCC receiving cisplatin-based IC followed by CCRT from January 1, 2006, through January 1, 2012. Immunohistochemistry was used to assess OPN expression in OSCC patients’ biopsy specimens from paraffin blocks before treatment. In addition, MTT/colony formation assay was used to estimate the influence of OPN in an oral cancer cell line treated with cisplatin.Results.Of the 121 patients, 94 had positive OPN findings and 52 responded to IC followed by CCRT. Positive osteopontin immunostaining also correlated significantly with positive N status/TNM stage/male gender and smoking. Univariate analyses showed that patients whose tumors had a low expression of OPN were more likely to respond to chemotherapy and have a significantly better OS than those whose tumors had a high expression of OPN. Multivariate analysis revealed that prolonged survival was independently predicted for patients with stage IVA disease, negative lymph nodes, and negative expressions of OPN and for those who received chemotherapy with Docetaxel/cisplatin/fluorouracil (TPF). An oral cancer line stimulated with OPN exhibited a dose-dependent resistance to cisplatin treatment. Conversely, endogenous OPN depletion by OPN-mediated shRNA increased sensitivity to cisplatin.Conclusions.A positive expression of OPN predicts a poor response and survival in patients with locally advanced stage IVA/B OSCC treated with cisplatin-based IC followed by CCRT.

Author(s):  
Amit Dhawan

AbstractOral squamous cell carcinoma is the third most common cancer in Indian subcontinent affecting people with lower socioeconomic status. Due to inadequate screening facilities and lack of awareness among individuals most of the oral cancer cases are detected at an advanced stage. As early stage oral squamous cell carcinoma patients can be treated with single modality treatment (surgery or radical radiotherapy), multimodality regimen (surgery followed by concurrent chemoradiation) is adopted for high risk advanced stage cancers with multiple adverse features like extra nodal extension, lymphovascular invasion and perineural spread. The chapter outlines the principles of adjunctive therapy in oral cancer patients with special reference to different techniques, indications of radiotherapy and role of chemotherapeutic regimes in improving the overall survival of advanced stage oral cancer patients.


Author(s):  
Mehwish Feroz Ali

Oral cancer, the most challenging and life threatening disease in the field of dentistry, may start as a reactive lesion due to constant stimulus from tobacco consumption, transform into a pre-malignant lesion (dysplastic lesion) and ultimately develop into a cancerous lesion (Invasive carcinoma). There is a fundamental revolution taking place in the analyzing methods; extraction of biological protein from the saliva rather than from tissues or blood. Several of the biomarkers have been studied with pro-carcinogenic effects like Interleukins (ILs), tumor necrosis factor (TNF) and leptin, but only a few have been stated in the literature, which show anti-cancer characteristics like adiponectin and zinc alpha-2 glycoprotein. This review explored the diagnostic and prognostic values of a biomarkers zinc alpha-2 glycoprotein (ZAG) in adults suspected of oral squamous cell carcinoma (OSCC). The PubMed, EMBASE and Google Scholar were searched for scientific studies reported on the potential mechanism of zinc alpha-2 glycoprotein. All the research articles were selected in which ZAG is applied solely or in conjunction with other biomarkers in oral cancer and other cancers. These literatures were carefully assessed to find out and compile the diagnostic and prognostic values and to inquire therapeutic action of ZAG in the process of carcinogenesis.


2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Wen Chen ◽  
Chenzhou Wu ◽  
Yafei Chen ◽  
Yuhao Guo ◽  
Ling Qiu ◽  
...  

AbstractC18 ceramide plays an important role in the occurrence and development of oral squamous cell carcinoma. However, the function of ceramide synthase 1, a key enzyme in C18 ceramide synthesis, in oral squamous cell carcinoma is still unclear. The aim of our study was to investigate the relationship between ceramide synthase 1 and oral cancer. In this study, we found that the expression of ceramide synthase 1 was downregulated in oral cancer tissues and cell lines. In a mouse oral squamous cell carcinoma model induced by 4-nitroquinolin-1-oxide, ceramide synthase 1 knockout was associated with the severity of oral malignant transformation. Immunohistochemical studies showed significant upregulation of PCNA, MMP2, MMP9, and BCL2 expression and downregulation of BAX expression in the pathological hyperplastic area. In addition, ceramide synthase 1 knockdown promoted cell proliferation, migration, and invasion in vitro. Overexpression of CERS1 obtained the opposite effect. Ceramide synthase 1 knockdown caused endoplasmic reticulum stress and induced the VEGFA upregulation. Activating transcription factor 4 is responsible for ceramide synthase 1 knockdown caused VEGFA transcriptional upregulation. In addition, mild endoplasmic reticulum stress caused by ceramide synthase 1 knockdown could induce cisplatin resistance. Taken together, our study suggests that ceramide synthase 1 is downregulated in oral cancer and promotes the aggressiveness of oral squamous cell carcinoma and chemotherapeutic drug resistance.


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.


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