scholarly journals SPINK7 Expression Changes Accompanied by HER2, P53 and RB1 may be Potential Biomarkers to Predict Oral Squamous Cell Carcinoma at Molecular Level

2020 ◽  
Author(s):  
Gina Penachiotti ◽  
Fabio Valdez ◽  
Wilfredo A González-Arriagada ◽  
Hector F Montes ◽  
Judith Parra ◽  
...  

Abstract Background. The oral squamous cell carcinoma (OSCC) affects more than 300,000 patients annually worldwide with a high morbidity rate (37.8%). Several tumor biomarkers have been suggested to anticipate outcome but results were poor. Changes of SPINK7 and associated proteins in precancerous oral lesions could lead to genomic instability and promote oncogenesis. Our aim was to evaluate SPINK7as apotential molecular biomarkerpredictive of OSCC stages, compared with well-known molecules altered in cancer: HER2,TP53, RB1, NFKB and CYP4B1. Methods.Oral biopsies from patientswith dysplasia (n=33), less invasive(n=28) andhighly invasiveOSCC (n=18) were collected. 20 cases with a clinical suspicion but normal mucosa confirmedwere included ascontrol. Gene expression of SPINK7, P53,RB, NFKBand CYP4B1 were quantified by qPCR.SPINK7 levels were correlated with a cohort of 330 patients from the TCGA. Also,SPINK7, HER2, TP53, and RB1, were evaluated by immunohistofluorescence. One-way Kruskal-Wallis test and Dunn's post-hocwith a p<0.05 significance were used to data analyze.Results.In OSCC, SPINK7wasdown regulated andP53, RB, NFKB and CYP4B1were up regulatedrespect tothe others groups (p<0.001). Also,SPINK7 expressionwasdiminished in patients of TCGA(p=2.10e-6). In less invasive OSCC,SPINK7 and HER2 proteinswere decreasedandTP53 and RB1 significantly increasedrespect todysplasia and highly invasivegroups (p<0.05).Conclusion. Our results suggest that SPINK7changes accompanied of HER2, P53 and RB1 can be used to classify the molecular stage of epithelial oral lesion inthe OSCC, allowing a more accuratediagnosis to molecular and histopathological level.

2020 ◽  
Author(s):  
Gina Pennacchiotti ◽  
Fabio Valdés Garrido ◽  
Wilfredo González-Arriagada ◽  
Héctor Montes ◽  
Judith Parra ◽  
...  

Abstract The oral squamous cell carcinoma (OSCC) affects patients worldwide with a high morbidity rate. Changes of SPINK7 in precancerous lesions could promote oncogenesis. Our aim was to evaluate SPINK7 as a potential molecular biomarker predictive of OSCC stages, compared with: HER2, TP53, RB1, NFKB and CYP4B1. Oral biopsies from patients with dysplasia (n=33), less invasive (n=28) and highly invasive OSCC (n=18) were used. 20 cases with a clinical suspicion but normal mucosa confirmed were the control. Gene levels of SPINK7, P53, RB, NFKB and CYP4B1 were quantified by qPCR. SPINK7 levels were correlated with a cohort of 330 patients from the TCGA. Also, SPINK7, HER2, TP53, and RB1, were evaluated by immunohistofluorescence. One-way Kruskal-Wallis test and Dunn's post-hoc with a p<0.05 significance was used to data analyze. In OSCC, SPINK7 expression was down regulated and P53, RB, NFKB and CYP4B1 were up regulated (p<0.001). Also, SPINK7 was diminished in TCGA patients (p=2.10e-6). In less invasive OSCC, SPINK7 and HER2 proteins were decreased and TP53 and RB1 increased respect to others groups (p<0.05). Our results suggest that SPINK7 changes accompanied of HER2, P53 and RB1 can be used to classify the molecular stage of OSCC lesions, allowing a diagnosis to molecular and histopathological level.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Gina Pennacchiotti ◽  
Fabio Valdés-Gutiérrez ◽  
Wilfredo Alejandro González-Arriagada ◽  
Héctor Federico Montes ◽  
Judith Maria Roxana Parra ◽  
...  

AbstractThe oral squamous cell carcinoma (OSCC), which has a high morbidity rate, affects patients worldwide. Changes in SPINK7 in precancerous lesions could promote oncogenesis. Our aim was to evaluate SPINK7 as a potential molecular biomarker which predicts OSCC stages, compared to: HER2, TP53, RB1, NFKB and CYP4B1. This study used oral biopsies from three patient groups: dysplasia (n = 33), less invasive (n = 28) and highly invasive OSCC (n = 18). The control group consisted of clinically suspicious cases later to be confirmed as normal mucosa (n = 20). Gene levels of SPINK7, P53, RB, NFKB and CYP4B1 were quantified by qPCR. SPINK7 levels were correlated with a cohort of 330 patients from the TCGA. Also, SPINK7, HER2, TP53, and RB1, were evaluated by immunohistofluorescence. One-way Kruskal–Wallis test and Dunn's post-hoc with a p < 0.05 significance was used to analyze data. In OSCC, the SPINK7 expression had down regulated while P53, RB, NFKB and CYP4B1 had up regulated (p < 0.001). SPINK7 had also diminished in TCGA patients (p = 2.10e-6). In less invasive OSCC, SPINK7 and HER2 proteins had decreased while TP53 and RB1 had increased with respect to the other groups (p < 0.05). The changes of SPINK7 accompanied by HER2, P53 and RB1 can be used to classify the molecular stage of OSCC lesions allowing a diagnosis at molecular and histopathological levels.


2021 ◽  
Vol 11 (2) ◽  
pp. 308-314
Author(s):  
Zengbo Wu ◽  
Yan Yan ◽  
Xianzhuo Chen ◽  
Yanling Liu ◽  
Dinggen Chen

miR15b and SALL4 are involved in a variety of tumor progression. The roles of miR15b and SALL4 in oral squamous cell carcinoma (OSCC) remains unclear. The tumors and normal mucosa of OSCC patients were collected to detect miR15b and SALL4 level by Real-time PCR and analyze their correlation with OSCC clinicopathological features. Oral cancer Tca8113 cells were separated into control group; miR15b mimics group and miR15b inhibitor group followed by analysis of SALL4 expression, cell survival by MTT assay; cell invasion by Transwell chamber assay, as well as expression of N-cadherin and Vimentin and correlated with TNM stage, tumor volume and metastasis, and positively with differentiation TGF-β by Western blot. miR15b expression was decreased and SALL4 expression was increased in OSCC tumor tissues. miR15b was negatively degree (P < 0.05), whereas, opposite correlation of SALL4 with the above parameters was found (P < 0.05). miR15b and SALL4 were negatively correlated. MiR15b mimics significantly up-regulated MiR15b, decreased SALL4 expression, inhibited Tca8113 cell proliferation and invasion, as well as reduced N-cadherin, Vimentin and TGF-βexpression (P < 0.05). Opposite results were found in MiR15b inhibitor group. MiR15b expression is decreased and SALL 4 is increased in OSCC tumor tissues. MiR15b and SALL4 is closely related to OSCC clinicopathological features. MiR15b regulates the expression of EMT-related genes and TGF-β, thereby altering the proliferation and invasion of OSCC cells.


2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Yuyang Li ◽  
Jia Li ◽  
Jingchun Sun ◽  
Yingkun Liu ◽  
Dingkun Liu ◽  
...  

Purpose. To examine the expression of RAD51 in oral squamous cell carcinoma (OSCC) and analyze its connection with pathological grade, clinical stage, and lymphatic metastasis potential. Methods. For this study, 74 OSCC samples, 15 normal mucosa tissues, and 11 normal skin tissue samples were collected. RAD51 expression was investigated using immunohistochemistry. A follow-up visit was used to assess the prognosis of each patient. We compared RAD51 expression in oral mucosa epithelial cells (OMECs), keratinocytes, and tongue squamous cell carcinoma cells (TSCCs) by Western blot analysis. Results. RAD51 expression was higher in tumor cells than in normal mucosal tissues. In addition, RAD51 expression was associated with higher tumor differentiation (P<0.05). Also, RAD51 expression was higher (P<0.05) in patients with lymphatic metastases, and relapse rates were also higher in patients with elevated RAD51 levels (P=0.052). In addition, RAD51 expression levels were highest in the skin keratinocytes, followed by the TSCCs and OMECs. Conclusion. A strong positive correlation was found between RAD51 expression and the degree of malignancy in OSCC patients, suggesting that RAD51 could be an excellent prognostic indicator for OSCC patients.


2010 ◽  
Vol 7 (3) ◽  
pp. 351-358 ◽  
Author(s):  
Tara L. Johnson ◽  
Maria B. Lai ◽  
James C. K. Lai ◽  
Alok Bhushan

High morbidity and mortality associated with oral squamous cell carcinoma (OSCC) are largely attributable to late stage diagnosis. Despite significant advances in therapeutic strategies, the five-year survival rate for oral cancer remains at about 50%. A chemopreventive approach may be an effective alternative or adjunct to current therapies. Previous studies have shown anti-tumor effects of isoflavones in several cancers, including oral cancer. However, their mechanisms of action are still unclear. We hypothesized that isoflavones inhibit multiple signaling pathways implicated in oral carcinogenesis. To address our hypothesis, we investigated the effects of three isoflavone derivatives, genistein, biochanin A and daidzein, on SCC15 and SCC25 squamous cell carcinoma cell lines. In cell proliferation experiments, we found that genistein and biochanin A inhibited SCC15 and SCC25 cell growth with an IC50 of 50 μM. We also investigated the effect of isoflavones on ERK and Akt pathways. Our results, from western blot analysis, suggest that both genistein and biochanin A induced decreases in phosphorylation of ERK and Akt at treatment concentrations of 20, 50 and 100 μM. Taken together, our results clearly demonstrate a differential regulation of signaling pathways by various isoflavones in OSCC cell lines. Thus, tumor progression models can be utilized to study the preventive and therapeutic roles of isoflavones in oral cancer cell lines.


Cancers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 136 ◽  
Author(s):  
Natalia Tołoczko-Iwaniuk ◽  
Dorota Dziemiańczyk-Pakieła ◽  
Katarzyna Celińska-Janowicz ◽  
Ilona Zaręba ◽  
Agnieszka Klupczyńska ◽  
...  

Background: Oral squamous cell carcinoma remains a significant worldwide public health challenge, associated with high morbidity and mortality. Treatment of this type of cancer lacks effective medication. Moreover, there are very few specific biomarkers that are useful in early diagnosis or treatment optimisation. Proline metabolism may prove to be of importance in the search for new treatment modalities. Methods: To evaluate the significance of proline metabolism in the development of oral cancer, proline concentration was assessed in oral cancer tissue and normal oral mucosa. The results were compared to the clinical stage and histological grade of the tumours. Moreover, the expression of proteins involved in proline metabolism via proline dehydrogenase/oxidase (PRODH/POX, PPARγ, HIF1-α) was determined. In the next stage of the study, conducted on cell lines of tongue cancer treated with celecoxib, the aforementioned factors involved in proline metabolism were evaluated. Cellular viability and cell proliferation, as well as apoptosis, were also assessed. Results: Our research results indicate that a high intracellular proline concentration and expression of factors involved in its metabolism correlate with the clinical stage and histological grade of oral cancer. Moreover, we are the first researchers to demonstrate that celecoxib can affect proline metabolism, causing an increase in pro-apoptotic factors (PRODH/POX, PPARγ), reducing the expression of HIF-1α and activating apoptosis. Conclusions: Proline metabolism, due to its involvement in the process of apoptosis, can be of great importance in anticancer therapy. It appears that celecoxib, which influences the PRODH/POX pathway, may be a promising therapeutic compound in oral cancer treatment.


Author(s):  
Manjushree Nayak ◽  
Jayanta Kumar Panda ◽  
Sudha Smruti Mishra ◽  
Bijay Kumar Das

Oral squamous cell carcinoma (OSSC) is the 3rd most common form of malignancy in developed countries[1]. The tumour is composed of two basic components i e, the neoplastic cells and the reactive stroma. The stromal changes which indicate the propensity of tumour cells to infiltrate and metastasise can also be used as one of the prognostic indicator[4,5]. Use of Picrosirius red (PSR) stain along with circular polarising microscope is helpful to detect spread of malignancy and guides the treatment plan and assess prognosis[11]. The present study is aimed to analyse the various aspects of collagen fibres in relation with the different grades OSSC. 30 patients of OSCC of various grades and 10 cases of normal mucosa were evaluated and data analysed statistically using sigma scan pro image analysis software(SPSS). Observation: Thirty patients (male-19 and female -11) of OSCC of age group 47-60 years were analysed. There were 14 well differentiated (WDSCC), 12 moderately differentiated (MDSCC) and 4 poorly differentiated (PDSCC) cases. When examined under polarising microscope majority (85.7%) of WDSCC and 41.67% of MDSCC showed reddish orange (RO) collagen fibres whereas in PDSCC (50%) showed green yellow (GY) collagen fibres which is statistically significant (P=0.02).In WDSCC 57.14% and in MDSCC 50% had swirl(S) arrangement whereas in PDSCC 50% had crosss hatchet (CH) and bundle arrangement. This is again statistically significant (P=0.031).While examining the orientation of collagen fibres in WDSCC 71.43% and in MDSCC, 83.33% had parallel orientation whereas in PDSCC 75% showed non parallel orientation. This orientation is statistically significant (p.008). On comparing the nature of birefringence maximum cases of WDSCC (85.71%) and MDSCC (83.33%) revealed strong birefringence whereas in PDSCC 75% exhibited weak. (statistically significant p.001). Conclusion: PSR stain under polarising microscope is an adjunct to the routine staining for studying stromal changes. The colour, arrangement, orientation & birefringence changes reflect its gradual shift from WDSCC to PDSCC and may help as a diagnostic and prognostic tool in OSCC.


2012 ◽  
Vol 13 (2) ◽  
pp. 205-209 ◽  
Author(s):  
Maryam Amirchaghmaghi ◽  
Nooshin Mohtasham ◽  
Pegah Mosannen Mozaffari

ABSTRACT Aim To compare cyclooxygenase 2 expression (COX2-E) between normal, oral leukoplakia lesions and different grades of oral squamous cell carcinoma (SCC). Materials and methods Around 90 paraffin embedded blocks consisting of 45 SCC, 15 leukoplakia and 17 controls were selected for immunohistochemistry (IHC) for detection of COX2- E. COX2-E was divided in four grades, as A (0-10%), B (11-40%), C (41-70%) and D (> 70%) cellularity. Results Mean age of the patients was 55.17 ± 18.41 (M:57.92 ± 16.87, F:52.19 ± 19.74). A significant difference was found in COX2 expression between SCC total and, basal and spinous layers of leukoplakia (p < 0.05). COX2-E in spinous layer of normal tissue was significantly lower than SCC (p = 0.000). COX2-E was significantly different in SCC grade 3 and leukoplakia (p = 0.001) and normal tissue (p = 0.000). COX2-E was significantly higher in SCC grade 3 compared to leukoplakia (basal layer) (p = 0.000). Conclusion We showed a significant higher COX2-E in SCC lesions compared to leukoplakias and normal controls. In our study COX2-E was not significantly different in SCC grades 1, 2 and 3 (p > 0.05). How to cite this article Amirchaghmaghi M, Mohtasham N, Mozaffari PM. Comparison of COX2 Expression between Oral Squamous Cell Carcinoma, Leukoplakia and Normal Mucosa. J Contemp Dent Pract 2012;13(2):205-209.


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