scholarly journals Map1lc3b and Sqstm1 Modulated Autophagy for Tumorigenesis and Prognosis in Certain Subsites of Oral Squamous Cell Carcinoma

2018 ◽  
Vol 7 (12) ◽  
pp. 478 ◽  
Author(s):  
Pei-Feng Liu ◽  
Hsueh-Wei Chang ◽  
Jin-Shiung Cheng ◽  
Huai-Pao Lee ◽  
Ching-Yu Yen ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Disease Free Survival ◽  
Normal Tissues ◽  
Sequestosome 1 ◽  
Tumor Tissues ◽  
Poor Differentiation ◽  
Cancer Types

Oral squamous cell carcinoma (OSCC) is one of the most common cancer types worldwide and can be divided into three major subsites: buccal mucosal SCC (BMSCC), tongue SCC (TSCC), and lip SCC (LSCC). The autophagy marker microtubule-associated protein light chain 3B (MAP1LC3B) and adaptor sequestosome 1(SQSTM1) are widely used proteins to evaluate autophagy in tumor tissues. However, the role of MAP1LC3B and SQSTM1 in OSCC is not fully understood, particularly in certain subsites. With a tissue microarray comprised of 498 OSCC patients, including 181 BMSCC, 244 TSCC, and 73 LSCC patients, we found that the expression levels of MAP1LC3B and cytoplasmic SQSTM1 were elevated in the tumor tissues of three subsites compared with those in adjacent normal tissues. MAP1LC3B was associated with a poor prognosis only in TSCC. SQSTM1 was associated with poor differentiation in three subsites, while the association with lymph node invasion was only observed in BMSCC. Interestingly, MAP1LC3B was positively correlated with SQSTM1 in the tumor tissues of BMSCC, whereas it showed no correlation with SQSTM1 in adjacent normal tissue. The coexpression of higher MAP1LC3B and SQSTM1 demonstrated a significantly worse disease-specific survival (DSS) and disease-free survival (DFS) in patients with BMSCC and LSCC, but not TSCC. The knockdown of MAP1LC3B and SQSTM1 reduced autophagy, cell proliferation, invasion and tumorspheres of BMSCC cells. Additionally, silencing both MAP1LC3B and SQSTM1 enhanced the cytotoxic effects of paclitaxel in the tumorspheres of BMSCC cells. Taken together, MAP1LC3B and SQSTM1 might modulate autophagy to facilitate tumorigenesis and chemoresistance in OSCC, particularly in BMSCC.

Expression, Proliferation and Apoptosis of miR‑92b in Oral Squamous Cell Carcinoma

2020 ◽  
Author(s):  
Yongzhi XU ◽  
Fang FANG ◽  
Jinghui WANG ◽  
Chunli ZHAO ◽  
Jingyang ZHAO ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Expression Level ◽  
Normal Tissues ◽  
Tumor Tissues ◽  
Proliferation And Apoptosis ◽  
Proliferation Ability ◽  
Rat Tissue

Background: Expression of miR‑92b in oral squamous cell carcinoma (OSCC) rat tissue and its effect on the OSCC CAL‑27 cells were investigated. Methods: The study was performed in Qingdao Stomatological Hospital, Qingdao, China on December 2018. Thirty Wistar rats were used to construct models of oral squamous cell carcinoma. CAL‑27 cells trascfected by Lipofectamine 2000 were divided into miR‑92b inhibitor, miR‑NC and blank groups. RT‑qPCR was used for the detection of the expression level of miR‑92b, and MTT and flow cytometry were carried out for the detection of the effect of miR‑92b on the proliferation and apoptosis of CAL‑27 cells, respectively. Results: The expression level of miR‑92b was significantly higher in tumor tissues than that in normal tissues (P<0.001). The miR‑92b inhibitor group had significantly lower proliferation ability but higher apoptosis rate of CAL‑27 cells than the miR‑NC and blank groups. After miR‑92b was downregulated by trans-fecting cells, the expression level of miR‑92b was significantly lower in the miR‑92b inhibitor group than that in the miR‑NC and blank groups. Conclusion: miR‑92b inhibitor can inhibit the proliferation of CAL‑27 cells and promote apoptosis, which provides certain references for clinical treatment. It is expected to be a potential target for treating OSCC.

scholarly journals Effect of EGFR on SQSTM1 Expression in Malignancy and Tumor Progression of Oral Squamous Cell Carcinoma

2021 ◽  
Vol 22 (22) ◽  
pp. 12226
Author(s):  
Yu-Kai Tseng ◽  
Chun-Feng Chen ◽  
Chih-Wen Shu ◽  
Cheng-Hsin Lee ◽  
Yan-Ting Chou ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Growth ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Kinase Inhibitor ◽  
Expression Levels ◽  
Sequestosome 1 ◽  
Egfr Expression ◽  
Tumor Tissues

Oral squamous cell carcinoma (OSCC) is one of the most common types of malignant tumor. Sequestosome 1 (SQSTM1) serves as an adaptor of autophagy for degrading protein aggregates. The regulation of autophagy by EGFR and its clinical impacts are indicated in various types of cancer. However, the association of EGFR and SQSTM1 in OSCC is still unknown. Our results show that the expression levels of SQSTM1 and EGFR proteins are higher in tumor tissues than in the corresponding tumor-adjacent (CTAN) tissues of OSCC patients. The expression levels of SQSTM1 were positively associated with the EGFR expression level. High co-expression of SQSTM1 and EGFR is associated with poor prognosis in OSCC patients. Moreover, SQSTM1 expression is decreased in EGFR-knockdown cells. Cell growth and invasion/migration are also decreased in cells with single/combined knockdowns of EGFR and SQSTM1 or in SQSTM1-knockdown cells without EGFR kinase inhibitor Lapatinib treatment compared to that in scrambled cells. However, cell growth and invasion/metastasis were not significantly different between the scrambled cells and SQSTM1-knockdown cells in the presence of Lapatinib. This study is the first to indicate the biological roles and clinical significance of SQSTM1 regulation by EGFR in OSCC.

scholarly journals Identification and Validation of PLOD2 as an Adverse Prognostic Biomarker for Oral Squamous Cell Carcinoma

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1842
Author(s):  
Yawei Sun ◽  
Shuai Wang ◽  
Xingwei Zhang ◽  
Zhuhao Wu ◽  
Zihui Li ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Prognostic Biomarker ◽  
Spatial Expression ◽  
Protein Levels ◽  
Normal Tissues ◽  
Tumor Tissues ◽  
Mesenchymal Transformation

Background: Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2), a key enzyme that catalyzes the hydroxylation of lysine, plays a crucial role in the progression of several solid tumors. However, its spatial expression profile and prognostic significance in oral squamous cell carcinoma (OSCC) have not been revealed. Materials: Mass spectrometry was used to explore amino acid perturbations between OSCC tumor tissues and paired normal tissues of 28 patients. Then, PLOD2 mRNA and protein levels were assessed using several public databases and 18 pairs of OSCC patients’ tissues. Additionally, PLOD2 spatial expression profiles were investigated in 100 OSCC patients by immunohistochemistry and its diagnostic and prognostic values were also evaluated. Lastly, gene set enrichment analysis (GSEA) was used to investigate the potential functions of PLOD2 in OSCC. Results: Lysine was significantly elevated in OSCC tissues and could effectively distinguish tumor from normal tissues (AUC = 0.859, p = 0.0035). PLOD2 mRNA and protein levels were highly increased in tumor tissues of head and neck squamous cell carcinoma (HNSCC) (p < 0.001) and OSCC compared with those in nontumor tissues (p < 0.001). Histopathologically, PLOD2 was ubiquitously expressed in tumor cells (TCs) and fibroblast-like cells (FLCs) of OSCC patients but absent in tumor-infiltrating lymphocytes (TILs). Patients with highly expressed PLOD2 in TCs (PLOD2TCs) and FLCs (PLOD2FLCs) showed poor differentiation, a worse pattern of invasion (WPOI) and more lymph node metastasis (LNM), contributing to higher postoperative metastasis risk and poor survival time. However, PLOD2FLCs rather than PLOD2TCs was an independent risk factor for survival outcomes in OSCC patients. Molecularly, GSEA demonstrated highly expressed PLOD2 was mainly enriched in epithelial–mesenchymal transformation (EMT), TGF-beta signaling and hypoxia pathway, which are associated with poor clinical outcomes of OSCC patients. Conclusions: PLOD2 was a poor prognostic biomarker for OSCC patients and may affect the metastasis of OSCC through EMT pathway. These findings might shed novel sights for future research in PLOD2 targeted OSCC therapy.

Relationship Between mir15b and Sal-Like Protein 4 and Biological Behavior of Oral Squamous Cell Carcinoma

2021 ◽  
Vol 11 (2) ◽  
pp. 308-314
Author(s):  
Zengbo Wu ◽  
Yan Yan ◽  
Xianzhuo Chen ◽  
Yanling Liu ◽  
Dinggen Chen
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Normal Mucosa ◽  
Clinicopathological Features ◽  
Biological Behavior ◽  
Control Group ◽  
Tumor Tissues ◽  
Proliferation And Invasion

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.

MET ectodomain shedding is associated with poor disease-free survival of patients diagnosed with oral squamous cell carcinoma

2019 ◽  
Vol 33 (6) ◽  
pp. 1015-1032 ◽  
Author(s):  
Maria J. De Herdt ◽  
Senada Koljenović ◽  
Berdine van der Steen ◽  
Stefan M. Willems ◽  
Rob Noorlag ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Disease Free Survival ◽  
Ectodomain Shedding ◽  
Free Survival ◽  
Disease Free

scholarly journals MiR-21 Expression in the Tumor Stroma of Oral Squamous Cell Carcinoma: An Independent Biomarker of Disease Free Survival

PLoS ONE ◽  
2014 ◽  
Vol 9 (4) ◽  
pp. e95193 ◽  
Author(s):  
Nora Hedbäck ◽  
David H. Jensen ◽  
Lena Specht ◽  
Anne-Marie K. Fiehn ◽  
Marianne H. Therkildsen ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Disease Free Survival ◽  
Tumor Stroma ◽  
Free Survival ◽  
Disease Free

scholarly journals Prognostic biomarkers in oral squamous cell carcinoma: a systematic review

2017 ◽  
Author(s):  
César Rivera ◽  
Ana Karina de Oliveira ◽  
Rute Alves Pereira e Costa ◽  
Tatiane De Rossi ◽  
Adriana Franco Paes Leme
Keyword(s):  
Systematic Review ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Disease Free Survival ◽  
Sample Size Determination ◽  
Free Survival ◽  
Cause Specific Survival

ABSTRACTOver the years, several tumor biomarkers have been suggested to foresee the prognosis of oral squamous cell carcinoma (OSCC) patients. Here, we present a systematic review to identify, evaluate and summarize the evidence for OSCC reported markers. Eligible studies were identified through a literature search of MEDLINE/PubMed until January 2016. We included primary articles reporting overall survival, disease-free survival and cause-specific survival as outcomes. Our findings were analysed using REporting recommendations for tumor MARKer prognostic studies (REMARK), QuickGo tool and SciCurve trends. We found 41 biomarkers, mostly proteins evaluated by immunohistochemistry. The selected studies are of good quality, although, any study referred to a sample size determination. Considering the lack of follow-up studies, the molecules are still potential biomarkers. Further research is required to validate these biomarkers in well-designed clinical cohort-based studies.

scholarly journals Identification of lysine acetylome of oral squamous cell carcinoma by label-free quantitative proteomics

2021 ◽  
Author(s):  
Jingjing Dong ◽  
Jingquan He ◽  
Zeyu Zhang ◽  
Wei Zhang ◽  
Yixi Li ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Signaling Pathway ◽  
Squamous Cell ◽  
Cellular Response ◽  
Enrichment Analysis ◽  
Lysine Acetylation ◽  
Label Free ◽  
Normal Tissues

Abstract Background Lysine acetylation (Kac) favors gene transcription and activates various genes involved in the regulation of oncogenesis, whereas the acetylation profiling of oral squamous cell carcinoma (OSCC) is unknown. We performed lysine acetylation analyses to achieve a comprehensive profile and revealed the specific pathogenesis in patients with OSCC. Methods Liquid chromatography − tandem mass spectrometry (LC-MS/MS) was utilized to investigate lysine acetylation features of tumor tissues and adjacent normal tissues from 9 patients with OCSS. Results Among the upregulated different acetylation proteins (DAPs), the biological process of GO analysis was closely related to cellular response to regulation of apoptotic process, and regulation of programmed cell death. KEGG enrichment analysis was associated with HIF-1 signaling pathway, ferroptosis, and JAK-STAT signaling pathway. In PPI network, seven differently Kac proteins (SRSF1, HNPNPM, PRPF8, DHX9, DHX15, RBMX, SNRPG) in MCODE1 and the top 30 hub gene involved in mRNA splicing process and spliceosome pathway. Six differently Kac modified proteins of RPS15A, RPL11, RPS11, RPS3, RPL24, RPL19 in MCODE1 was enriched in ribosome pathway, particular lower expression of RPS3, RPL24 and RPL19 were related to the overall survival of OSCC. Conclusion This study contributes a foundation for understanding the functions of Kac modification in OSCC and investigates lysine acetylation on proteins involved in ribosome pathway, particularly the ones that acted as hub genes and related to the OSCC survival, which may be a potential therapeutic direction of OSCC in the future.

scholarly journals CD38 Multi-Functionality in Oral Squamous Cell Carcinoma: Prognostic Implications, Immune Balance, and Immune Checkpoint

2021 ◽  
Vol 11 ◽  
Author(s):  
Zhuang Ding ◽  
Yijia He ◽  
Yong Fu ◽  
Nisha Zhu ◽  
Mengxiang Zhao ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Tumor Cells ◽  
Squamous Cell ◽  
Immune Checkpoint ◽  
Disease Free Survival ◽  
Immune Microenvironment ◽  
Immune Checkpoint Molecules ◽  
Immune Balance

BackgroundCD38 belongs to the ribosyl cyclase family and is expressed on various hematological cells and involved in immunosuppression and tumor promotion. Although targeting CD38 antibodies has been approved for treatment of multiple myeloma, the function of CD38 in solid tumor, oral squamous cell carcinoma (OSCC) etc., has not been investigated.MethodsThis retrospective study included 92 OSCC samples and analyzed the spatial distribution of CD38 by immunohistochemistry (IHC). The values of diagnosis and prognosis of CD38 were evaluated. Additionally, 53 OSCC preoperative peripheral blood samples were used to be analyzed by flow cytometry. Tumor Immune Estimation Resource (TIMER) and cBioPortal databases were used to study CD38 level in various tumors and its correlation with tumor immune microenvironment in head and neck squamous cell carcinoma (HNSCC).ResultsCD38 ubiquitously presented in tumor cells (TCs), fibroblast-like cells (FLCs), and tumor-infiltrating lymphocytes (TILs). Patients with highly expressed CD38 in TCs (CD38TCs) had higher TNM stage and risk of lymph node metastasis. Upregulation of CD38 in FLCs (CD38FLCs) was significantly associated with poor WPOI. Escalated CD38 in TILs (CD38TILs) led to higher Ki-67 level of tumor cells. Moreover, patients with enhanced CD38TCs were susceptible to postoperative metastasis occurrence, and those with highly expressed CD38TILs independently predicted shorter overall and disease-free survival. Strikingly, patients with highly expressed CD38TILs, but not CD38TCs and CD38FLCs, had significantly lower CD3+CD4+ T cells and higher ratio of CD3−CD16+CD56+NK cells. The imbalance of immune system is attributed to dysregulated immune checkpoint molecules (VISTA, PD-1, LAG-3, CTLA-4, TIGIT, GITR) as well as particular immune cell subsets, which were positively correlated with CD38 expression in HNSCC.ConclusionCD38 is a poor prognostic biomarker for OSCC patients and plays a vital role in governing immune microenvironment and circulating lymphocyte homeostasis. Co-expression between CD38 and immune checkpoint molecules provides new insight into immune checkpoint therapy.

scholarly journals Association of SP1 rs1353058818 and STAT3 rs1053004 gene polymorphisms with human tongue squamous cell carcinoma

2019 ◽  
Vol 39 (7) ◽  
Author(s):  
Heqing Lai ◽  
Guochao Xu ◽  
Haifeng Meng ◽  
Haiying Zhu
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Gene Polymorphisms ◽  
Protective Factor ◽  
Tongue Squamous Cell Carcinoma ◽  
Normal Tissues ◽  
Human Tongue ◽  
Tumor Tissues ◽  
High Risk Factor

Abstract Objective: To study the association between SP1 rs1353058818 and STAT3 rs1053004 gene polymorphisms and risk of human tongue squamous cell carcinoma (TSCC). Methods: Sanger sequencing was used to determine the genotypes of SP1 rs1353058818 and STAT3 rs1053004 loci in 240 TSCC patients and 240 controls. Levels of hsa-miR-149-5p and hsa-miR-21-5p and expression levels of SP1 and STAT3 proteins in tumor tissues and adjacent normal tissues of TSCC patients were ascertained. Results: Carrying the SP1 rs1353058818 locus deletion allele was a high risk factor for TSCC (OR = 2.997, 95% CI: 1.389–6.466, P = 0.003). The STAT3 rs1053004 locus A allele was a protective factor for TSCC (OR = 0.604, 95% CI: 0.460-0.793, P < 0.001). There was a negative correlation between SP1 mRNA and hsa-miR-149-5p in tumor and adjacent normal tissues (r = −0.81, −0.77). The expression of SP1 protein in tumor tissues of the SP1 rs1353058818 locus DD genotype was significantly higher than in tissues of the ID type, and in tissues of type II it was the lowest. STAT3 mRNA was positively correlated with hsa-miR-21-5p in tumor and adjacent normal tissues (r = 0.75, 0.78). The expression level of STAT3 protein in tumor tissues of patients with STAT3 rs1053004 locus GG genotype was significantly higher than in patients with type GA, and it was the lowest in patients with type AA. Conclusion: Polymorphisms in the SP1 rs1353058818 and STAT3 rs1053004 loci are associated with the risk of human TSCC.

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