scholarly journals Up-Regulation of YTHDF1 and YTHDF3 is Related to the Prognosis of Oral Squamous Cell Carcinoma

Author(s):  
Rui Shi ◽  
Shao-ming Li ◽  
Ling Gao ◽  
Ke-qian Zhi ◽  
Ren Wen-Hao

Abstract Background N6-methyladenosine (m6A) is the most abundant internal modification in mammalian mRNAs. M6A is composed of methyl-transferases, which act as ("writers"), binding proteins, which act as ("readers"), and demethylases, which act as ("erasers"). As an important part of ("readers"), YTHDF1 and YTHDF3 were shown to be associated with many cancers. This paper aimed to study the expression of YTHDF1 and YTHDF3 in oral squamous cell carcinoma (OSCC). Methods We detected the expression of YTHDF1 and YTHDF3 in 120 OSCC patients by immunohistochemical analysis. Statistical analysis was used to determine whether the high or low expression of these two genes was significantly associated with age, gender, histological type, clinical stage, or lymph node metastasis. The correlation curve and survival curve of the two genes were produced to evaluate the potential clinical significance. Results We find the expression of YTHDF1 and YTHDF3 was increased in OSCC tissues compared to adjacent normal tissues。The statistical analysis showed that the expression of YTHDF1 and YTHDF3 was significantly associated with the clinical stage and histological type in OSCC patients. There was also a significant correlation between the expression of YTHDF1 and YTHDF3. A high expression of YTHDF1 and YTHDF3 was related to poor patient prognosis. Conclusions Our findings suggest that a high expression of YTHDF1 and YTHDF3 may be related to poor patient prognosis.

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Ping Zhou ◽  
Lei Xiao ◽  
Xiaonan Xu

Abstract Background As a tumor-accelerating transcriptional factor, E2F transcription factor 7 (E2F7) was up-regulated in many forms of cancers. Nevertheless, little has been reported about the impacts of E2F7 on oral squamous cell carcinoma (OSCC). Here, we aimed to probe whether E2F7 had influences on OSCC and its potential mechanism. Methods The expression of E2F7 in OSCC tissues was analyzed using the data acquired from TCGA and ONCOMINE databases. E2F7 prognostic value in OSCC patients was analyzed utilizing TCGA database. The expression of E2F7 in OSCC cell lines was detected by qRT-PCR. Gain-and loss-function of E2F7 assays in TCA-83 and CAL27 cells were performed respectively to inquire the function of E2F7. Western blotting was applied to test the alternations of EMT-related markers. Results In OSCC tissues, E2F7 was highly expressed. Besides, high expression of E2F7 predicted worse prognosis in OSCC patients. Moreover, E2F7 was over-expressed in TCA-83, HSC-4 and CAL27 (all OSCC cell lines) cells relative to that in HNOK (a normal cell line) cells. Gain-and loss-function assays displayed that deficiency of E2F7 suppresses CAL27 cell growth, migration, invasion and E2F7 high-expression resulted in inverse outcomes in TCA-83 cells. Finally, we found that silencing of E2F7 facilitated E-cadherin protein expression level and reduced N-cadherin, Vimentin and Snail protein levels in CAL27 cells, whilst E2F7 high-expression exhibited the opposite effects in TCA-83 cells. Conclusions These outcomes indicated that E2F7 performs a carcinogenic role in OSCC, which provides a theoretical basis for the therapeutic strategies of OSCC.


2021 ◽  
Vol 11 (8) ◽  
pp. 1571-1575
Author(s):  
Guowu Ma ◽  
Jia Hou ◽  
Jiezi Qiu ◽  
Jianlin Fan ◽  
Jianxin Yang

Oral squamous cell carcinoma (OSCC) had the poor prognosis. miR-155 was involved in some diseases. However, whether BMSCs with high expression miR-155 affect the proliferation and metastasis of OSCC is unclear. Our study aims to assess BMSCs’ effect on OSCC cells. miR-155 level in OSCC tumor tissues was analyzed. BMSCs were transfected with miR-155 followed by analysis of cell proliferation by MTT assay, cell apoptosis and migration, and MMP-9 level by ELISA and PTEN12 level. In the tumor tissue, miR-155 level was significantly increased (P <0.05). Co-culture of BMSCs with high expression miR-155 with OSCC cells could significantly promote OSCC cell proliferation and reduced cell apoptotic activity, increased cell migration and MMP-9 secretion as well as downregualted PTEN12 expression (P <0.05). In conclusion, miR-155 was increased in the OSCC patients and BMSCs of high expression miR-155 could promote the proliferation and metastasis of OSCC by regulating PTEN12.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6052-6052
Author(s):  
Lai-Ping Zhong ◽  
Wu-tong Ju ◽  
Rong-hui Xia ◽  
Qi Zhu ◽  
Guopei Zhu ◽  
...  

6052 Background: In patients with locally advanced oral squamous cell carcinoma (LAOSCC), major pathologic response (MPR) to induction therapy may translate into improved survival. The induction therapy using chemo-free drugs, such as the combination of anti-PD1 and anti-VEGFR drugs, has not been well issued in LAOSCC. Methods: A prospective single arm trial (NCT04393506) has been performed to evaluate the induction therapy of anti-PD1 and anti-VEGFR protocol in LAOSCC patients at clinical stage III and IVA. The patients received three cycles of intravenous Camrelizumab (PD-1 antibody, 200mg) on d1, d15, d29; and oral Apatinib (anti-VEGFR inhibitor, 250mg) daily, initiating on d1, ending on the 5th day before surgery. Radical surgery was planned on d42-d45. Post-operative radiotherapy was planned within 1.5 months after surgery, based on clinical and pathological stage. The primary endpoints were MPR and safety; primary tumors were assessed for the percentage of residual viable tumor that was identified on HE staining, and tumors with no more than 10% viable tumor cells were considered as MPR. This study has been approved by institutional ethics committee at Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine. Results: From April to December 2020, 21 patients were enrolled in this trial, and one patient withdraw from the trial at the beginning of treatment. The induction therapy was well-tolerated with no grade 3-4 toxicity or serve induction therapy-related AEs. One patient required surgery delay for 7 days due to unexplainable cTnI elevation. One patient put off Camrelizumab for 14 days due to grade 2 thrombocytopenia. One patient suspended Apatinib for 21 days due to grade 2 Hyperbilirubinemia. The induction therapy did not effect on the subsequent standard treatment. MPR rate was 40% (8/20), including 5% (1/20) pCR. Radiological evaluation of response to induction therapy showed 3 PR, 10 SD, 5 PD and 2 NA. Weak correlation was found between pathologic and radiological evaluation on induction therapy. Combined positive score (CPS) of PD-L1 expression in biopsy was evaluated in 19 patients; all 4 patients with CPS≥ 20 had MPR, 3 out of 11 patients with 1≤CPS < 20 had MPR, and 1 out of 4 patients with CPS < 1 had MPR. Conclusions: The chemo-free protocol of induction therapy using Camrelizumab and Apatinib is safe and well-tolerated for the patients with LAOSCC. The MPR rate is much higher using the anti-PD1 and anti-VEGFR protocol than the traditional induction chemotherapy protocol in LAOSCC. Clinical trial information: NCT04393506.


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.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15548-e15548
Author(s):  
Ritvi K Bagadia ◽  
Vishal Uchila Shishir Rao ◽  
Ajay Balakrishnan ◽  
Abhijith George ◽  
Prashant Kumar

e15548 Background: Around 90% of cancer-related mortalities are caused by tumor metastasis. CTC clusters, which constitute an intermediate stage of metastasis, have not been studied extensively in head & neck cancers. The mortality rate of oral cancers remains alarmingly high, despite multimodality treatment. The aim of the study is to identify the presence of CTC clusters in patients with Oral Squamous Cell Carcinoma (OSCC) and to correlate their presence with clinical and pathological factors. Methods: Fifty patients diagnosed with histologically proven OSCC, treatment naïve, and underwent surgery at HCG Cancer Centre, Bangalore, were consented and enrolled in the study. An IRB-approved protocol allowed for the collection of 10 ml of blood from central (jugular) and peripheral veins intra-operatively, prior to tumor removal. The culturing of CTC clusters was done using ellipsoidal microwell plates maintained at hypoxic conditions, at the Institute of Bioinformatics, Bangalore. After fourteen days of culturing, the cells were fixed and stained for DAPI, Pan-CK and CD45. The CTC clusters were classified into Loose, Tight and very Tight based on the median gray values obtained from DAPI staining on ImageJ software. Clinical data was collected from patient records and subjected to analysis using Descriptive statistics. Results: From the 50 patients included in the study, 22 (44%) patients exhibited tight clusters in central blood, while only 13 (26%) patients exhibited tight clusters in peripheral blood. A higher clinical stage was observed in a greater percentage of patients with tight clusters in central blood (early: 45.5% versus late: 54.5%), but the same findings could not be inferred with pathological staging (early stage: 59.1% versus late stage: 40.1%). No significant correlation with adverse pathological features was noted. Conclusions: This observational study provides an insight into the varying biological behaviours of similarly grouped cancers, which is based on the standard TNM staging. The study forms the basis for the hypothesis of tight clusters in the central and peripheral circulation, correlating with loco-regional and distant metastasis respectively, thus leading to poorer disease-free and overall survival rates.


2017 ◽  
Vol 37 (4) ◽  
Author(s):  
Hefei Li ◽  
Haibo Wang ◽  
Zhenqing Sun ◽  
Qiang Guo ◽  
Hongyun Shi ◽  
...  

Polo-like kinase 1 (PLK1) has been suggested to serve as an oncogene in most human cancers. The aim of our study is to present more evidence about the clinical and prognostic value of PLK1 in lung squamous cell carcinoma patients. The status of PLK1 was observed in lung adenocarcinoma, lung squamous cell carcinoma, and normal lung tissues through analyzing microarray dataset (GEO accession numbers: GSE1213 and GSE 3627). PLK1 mRNA and protein expressions were detected in lung squamous cell carcinoma and normal lung tissues by using quantitative real-time PCR (qRT-PCR) and immunohistochemistry. In our results, the levels of PLK1 in lung squamous cell carcinoma tissues were higher than that in lung adenocarcinoma tissues. Compared with paired adjacent normal lung tissues, the PLK1 expression was increased in lung squamous cell carcinoma tissues. Furthermore, high expression of PLK1 protein was correlated with differentiated degree, clinical stage, tumor size, lymph node metastasis, and distant metastasis. The univariate and multivariate analyses showed PLK1 protein high expression was an unfavorable prognostic biomarker for lung squamous cell carcinoma patients. In conclusion, high expression of PLK1 is associated with the aggressive progression and poor prognosis in lung squamous cell carcinoma patients.


2021 ◽  
Author(s):  
Yu-jie Liang ◽  
Xue-ying Mei ◽  
Bin Zeng ◽  
Si-en Zhang ◽  
Le Yang ◽  
...  

Abstract Background: The relationship between cancer and coagulation has been intensively studied in recent years; however, the effects of coagulation factors on oral squamous cell carcinoma (OSCC) have rarely been reported. This study aimed to investigate the relationship between preoperative D-dimer (DD), fibrinogen (FIB), platelets (PLT) and OSCC, as well as the prognostic value of DD, FIB and PLT in OSCC. Methods: We retrospectively investigated a total of 202 patients with OSCC treated at Guanghua Hospital of Stomatology, Sun Yat-sen University. Baseline demographic and clinicopathological information as well as both preoperative and postoperative DD, FIB and PLT results were collected from each patient, and patients with primary OSCC were followed up for disease progression, death or the end of the study. The correlations between preoperative DD, FIB, PLT and other clinical features, as well as the therapeutic effect and PFS were analysed statistically, and postoperative DD and surgical parameters were also analysed. Results: Preoperative DD was significantly correlated with T stage, N stage, clinical stage and relapse of OSCC ( P =0.000, 0.001, 0.000 and 0.000, respectively). Univariate Cox regression analyses showed that high preoperative DD predicted poor prognosis in patients with OSCC (HR=2.1, P =0.033), while FIB and PLT showed no prognostic values. Postoperative DD was significantly correlated with preoperative DD and surgical type but not the duration of surgery ( P =0.005, 0.001 and 0.244, respectively). Conclusion: In this study, we suggested that high preoperative DD level may serve as an indicator for synchronous neck dissection in patients with T 1, 2 OSCC, and the elevated DD level might be the marker of disease progression in patient follow up.


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