scholarly journals SPINK7 expression changes accompanied by HER2, P53 and RB1 can be relevant in predicting oral squamous cell carcinoma at a molecular 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.

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.


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.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Ling Mao ◽  
Xiaoweng Wu ◽  
Zhengpeng Gong ◽  
Ming Yu ◽  
Zhi Huang

Abstract Background/objective Accumulated evidence has demonstrated that aerobic glycolysis serves as a regulator of tumor cell growth, invasion, and angiogenesis. Herein, we explored the role of protein disulfide isomerase family 6 (PDIA6) in the aerobic glycolysis and the progression of oral squamous cell carcinoma (OSCC). Methods The expression pattern of PDIA6 in OSCC tissues was determined by qPCR and western blotting. Lentivirus and small interfering RNAs (siRNAs) were introduced into cells to upregulate and downregulate PDIA6 expression. CCK-8, flow cytometry, transwell, and xenotransplantation models were applied to detect cell proliferation, apoptosis, migration, invasion, and tumorigenesis, respectively. Results A high expression pattern of PDIA6 was observed in OSCC tissues, which was closely associated with lower overall survival and malignant clinical features in OSCC. Compared with the control group, overexpression of PDIA6 induced significant enhancements in cell growth, migration, invasiveness, and tumorigenesis and decreased cell apoptosis, while knockdown of PDIA6 caused opposite results. In addition, overexpression of PDIA6 increased glucose consumption, lactate production, and ATP level in OSCC cells. Conclusion This study demonstrated that PDIA6 expression was elevated in OSCC tissues, and overexpression of it promoted aerobic glycolysis and OSCC progression.


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.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sophia Mentel ◽  
Kathleen Gallo ◽  
Oliver Wagendorf ◽  
Robert Preissner ◽  
Susanne Nahles ◽  
...  

Abstract Background The aim of this study was to evaluate the possibility of breath testing as a method of cancer detection in patients with oral squamous cell carcinoma (OSCC). Methods Breath analysis was performed in 35 OSCC patients prior to surgery. In 22 patients, a subsequent breath test was carried out after surgery. Fifty healthy subjects were evaluated in the control group. Breath sampling was standardized regarding location and patient preparation. All analyses were performed using gas chromatography coupled with ion mobility spectrometry and machine learning. Results Differences in imaging as well as in pre- and postoperative findings of OSCC patients and healthy participants were observed. Specific volatile organic compound signatures were found in OSCC patients. Samples from patients and healthy individuals could be correctly assigned using machine learning with an average accuracy of 86–90%. Conclusions Breath analysis to determine OSCC in patients is promising, and the identification of patterns and the implementation of machine learning require further assessment and optimization. Larger prospective studies are required to use the full potential of machine learning to identify disease signatures in breath volatiles.


2018 ◽  
Vol 49 (4) ◽  
pp. 1329-1341 ◽  
Author(s):  
Nan Li ◽  
Chuan-Chuan Nan ◽  
Xue-Yun Zhong ◽  
Jun-Quan Weng ◽  
Hai-Dong Fan ◽  
...  

Background/Aims: Emerging evidence suggests that the propagation of oral squamous cell carcinoma (OSCC) is influenced by the abnormal expression of microRNAs (miRNAs). This study aimed to characterize the involvement of miR-182-5p in OSCC by targeting the calcium/ calmodulin-dependent protein kinase II inhibitor CAMK2N1. Methods: miR-182-5p expression was quantified in OSCC tissues and cell lines with reverse transcription polymerase chain reaction (RT-PCR). Cell colony formation, Cell Counting Kit-8 (CCK-8), Ki-67, and nude mouse xenograft assays were used to characterize the role of miR-182-5p in the proliferation of OSCC. A miR-182-5p target gene was identified with western blotting, RT-PCR, and luciferase activity assays. OSCC patient survival based on CAMK2N1 expression was also analyzed. Results: miR-182-5p was up-regulated in in vitro cell lines and in vivo clinical OSCC samples. CCK-8, colony formation, and Ki-67 assays revealed that miR-182-5p promoted the growth and proliferation of OSCC cells. miR-182-5p directly targeted CAMK2N1, as evidenced by luciferase assays and target prediction algorithms. CAMK2N1 operated as a tumor suppressor gene in patients with OSCC. Down-regulating miR-182-5p expression in the CAL-27 cell line restored CAMK2N1-mediated OSCC cell proliferation. miR-182-5p expression inhibited the activation of AKT, ERK1/2, and NF-κB. Mice injected with CAL-27 cells transfected with miR-182-5p-inhibitor demonstrated a significant increase in tumor size and weight and increased CAMK2N1 mRNA and protein expression compared with the miR-negative control group. Conclusion: The miR-182-5p-CAMK2N1 pathway can be potentially targeted to regulate the proliferation of OSCC cells.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Ying Ma ◽  
Shujuan Qu ◽  
Liangpeng Xu ◽  
Hongbo Lu ◽  
Baoguo Li

Abstract Background The primary aim of this study was to observe the effect of 5-ALA-mediated photodynamic therapy on oral squamous cell carcinoma in vitro. Methods SCC25 cells were divided into the observation group and the blank control group. Different concentrations of 5-ALA and SCC25 cells were co-incubated for different times, and the concentration of protoporphyrin IX was detected by flow cytometry. SCC25 cells were divided into the 5-ALA group (100 mg/L), the laser irradiation group alone, the 5-ALA plus laser irradiation group, and the blank control group (0 mg/L 5-ALA), and the methyl thiazolyl tetrazolium (MTT) solution method was used (each group was incubated for 4, 8 and 12 h in turn). The cell survival rate was calculated. Using annexin V-fluorescein isothiocyanate/propidium iodide method, the apoptosis of SCC25 cells was detected by flow cytometry. Results The level of protoporphyrin IX in SCC25 cells increased with increased concentrations of 5-ALA and length of incubation. However, after 12 h, protoporphyrin IX level in SCC25 cells was gradually stabilized, and similar effect was obtained with 100 mg/L or more 5-ALA, indicating that the level of protoporphyrin IX in SCC25 cells was determined by 5-ALA concentration and incubation time. 5-ALA plus laser irradiation exerted an inhibitory effect on the growth of SCC25 cells, which was highly associated with drug dose and incubation time. Compared with the control group, laser irradiation alone or 5-ALA alone had no effect on the apoptosis of SCC25 cells. Different concentrations of 5-ALA combined with laser irradiation showed a remarkable effect of apoptosis, and a higher apoptosis rate was seen with higher drug concentrations. Conclusion 5-ALA-mediated photodynamic therapy affects the growth of SCC25 cells in vitro, which may provide a new idea for the clinical treatment of oral squamous cell carcinoma.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5593-5593
Author(s):  
Lai-ping Zhong ◽  
Chen-ping Zhang ◽  
Zhi-yuan Zhang ◽  
Guo-xin Ren ◽  
Wei Guo ◽  
...  

5593 Background: The role of induction chemotherapy in locally advanced and resectable oral squamous cell carcinoma has not been well issued. Methods: A prospective, open label, parallel, and interventional randomized control trail has been performed to evaluate the induction chemotherapy of TPF protocol in resectable oral squamous cell carcinoma (OSCC) patients at clinical stage III and IVA. The patients received two cycles of TPF induction chemotherapy (75 mg/m2 docetaxel d1, 75mg/m2 cisplatin d1, and 750mg/m2 5-fluorouracil d1-5) followed by radical surgery and post-operative radiotherapy with a dose from 54 to 66 Gy (the experimental group) or surgery and post-operative radiotherapy (the control group). Post-surgical pathologic examination was performed to determine a positive response or negative response. A positive response was defined as absence of any tumor cells (pathologic complete response) or presence of scattered foci of a few tumor cells (minimal residual disease with <10% viable tumor cells). The primary endpoint is the survival rate; the secondary endpoint is the local control and safety. This study has been approved by institutional ethics committee at Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University. Survival analysis was conducted with the Kaplan-Meier method. Results: 256 patients were enrolled in this trail and 224 patients (111 in experiment group and 113 in control group) finished the whole treatment protocol. After a median follow-up of 21 months (ranging 6-43 m). The pathologic positive response rate was 29.7% (33/111), and negative response rate was 70.3% (78/111). The patients with positive response had a better disease free survival (38.5±2.1m, 95%CI 34.4-42.6m, P=0.003) compared with those with negative response (24.6±2.1m, 95%CI 20.6-28.7m) and control group (31.0±1.6m, 95%CI 27.9-34.1m). The toxicity of induction chemotherapy could be tolerated. Conclusions: Pathologic positive response to TPF induction chemotherapy could benefit the patients with locally advanced and resectable OSCC. However, further long-term follow-up is needed to confirm the benefit on survival and local control.


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.


2019 ◽  
Vol 15 (2) ◽  
pp. 125-127
Author(s):  
Krishan Kumar Tyagi ◽  
Megha Pradhan ◽  
Rajbir Kaur Grewal ◽  
Prabesh Sherchan ◽  
KSA Pasha

Background: Head and neck malignancies include malignancies instigating in the oral cavity, the orophar-ynx, the hypopharynx and the larynx. We planned the present study to assess the role of human papilloma virus (HPV) in patients with oral squamous cell carcinoma (OSCC). Methods: The present study included assessment of role of human papilloma virus in patients with oral squamous cell carcinoma. A total of 50 histopathologic proven cases of well differentiated OSCC were included in the present study. A total of 50 healthy oral mucosal tissues (controls) were also included in the present study. The controls were obtained while surgical removing the impacted teeth. DNA was obtained from the tissue sections and underwent Polymerization chain reaction for identification of HPV 16/18. All the results were summarized in Microsoft excel sheet and were analyzed by SPSS software. Results: HPV was absent in all the cases of control group, whereas among the OSCC group, the HPV was detected in 46 percent of the cases. In the remaining 54 per-cent of the cases of the OSCC group, HPV was absent. Significant results were obtained while comparing the presence of HPV in between the OSCC group and the control group. Conclusions: HPV was present in sig-nificant number of OSCC cases. Therefore; HPV might play a contributing role in the etio-pathogenesis of OSCC.


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