Socio-demographic characteristics are related to the advanced clinical stage of oral cancer

Genetic and acquired factors are thought to be interrelated and imperative to estimate the risk and prognosis of oral squamous cell carcinoma (OSCC). HOX transcript antisense intergenic RNA ( HOTAIR) plays crucial roles in gene regulation and is regulated in a variety of cancers. Polymorphisms in HOTAIR have been recently linked to the predisposition to diverse malignancies. In the present study, we aimed to evaluate the influences of HOTAIR gene polymorphisms, combined with environmental triggers, on the susceptibility to oral tumorigenesis. Four single-nucleotide polymorphisms of the HOTAIR gene— rs920778, rs1899663, rs4759314, and rs12427129—were tested in 1,200 control participants and 907 patients with OSCC. We detected a significant association of rs1899663 with the risk of OSCC (adjusted odds ratio, 2.227; 95% confidence interval [95% CI], 1.197 to 4.146; P = 0.012) after adjustment for 3 potential confounders: smoking, betel quid chewing, and alcohol consumption. In further analyses where habitual exposure to each of 3 environmental factors was excluded, we found that, in addition to rs1899663, non–betel quid users who carried the polymorphic allele of rs920778 were more prone to develop OSCC than were those homozygous for wild-type allele (TC: odds ratio [OR], 1.472; 95% CI, 1.069 to 2.029; P = 0.018; TC+CC: OR, 1.448; 95% CI, 1.060 to 1.977; P = 0.020). Moreover, in exploring the relationship between HOTAIR gene polymorphisms and the clinical status of only patients with OSCC who were non–betel quid chewers (excluding the advanced clinical stage), we found that rs920778 and rs4759314 were correlated with the development of large-size tumors (OR, 1.891; 95% CI, 1.027 to 3.484; P = 0.04) and increased lymph node metastasis (OR, 4.140; 95% CI, 1.785 to 9.602; P = 0.001), respectively. Further functional assessments link rs920778 to the regulation of HOTAIR expression and epigenetic status. Our results reveal an interactive effect of HOTAIR gene polymorphisms and betel quid chewing on the development and progression of oral cancer.

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Glycoprotein B7-H3 overexpression and aberrant glycosylation in oral cancer and immune response

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1516991112 ◽

2015 ◽

Vol 112 (42) ◽

pp. 13057-13062 ◽

Cited By ~ 39

Author(s):

Jung-Tsu Chen ◽

Chein-Hung Chen ◽

Ko-Li Ku ◽

Michael Hsiao ◽

Chun-Pin Chiang ◽

...

Keyword(s):

Oral Cancer ◽

Cancer Cells ◽

Immune Cells ◽

Clinical Stage ◽

Intercellular Adhesion Molecule ◽

Tumor Cell Proliferation ◽

Advanced Clinical Stage ◽

Normal Cells ◽

Incidence And Mortality ◽

Oral Cancer Cells

The incidence and mortality rate of oral cancer continue to rise, partly due to the lack of effective early diagnosis and increasing environmental exposure to cancer-causing agents. To identify new markers for oral cancer, we used a sialylation probe to investigate the glycoproteins differentially expressed on oral cancer cells. Of the glycoproteins identified, B7 Homolog 3 (B7-H3) was significantly overexpressed in oral squamous cell carcinoma (OSCC), and its overexpression correlated with larger tumor size, advanced clinical stage, and low survival rate in OSCC patients. In addition, knockdown of B7-H3 suppressed tumor cell proliferation, and restoration of B7-H3 expression enhanced tumor growth. It was also found that the N-glycans of B7-H3 from Ca9-22 oral cancer cells contain the terminal α-galactose and are more diverse with higher fucosylation and better interaction with DC-SIGN [DC-specific intercellular adhesion molecule-3 (ICAM-3)–grabbing nonintegrin] and Langerin on immune cells than that from normal cells, suggesting that the glycans on B7-H3 may also play an important role in the disease.

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IGF2BP2 Polymorphisms Are Associated with Clinical Characteristics and Development of Oral Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms21165662 ◽

2020 ◽

Vol 21 (16) ◽

pp. 5662

Author(s):

Chia-Hsuan Chou ◽

Chien-Yuan Chang ◽

Hsueh-Ju Lu ◽

Min-Chien Hsin ◽

Mu-Kuan Chen ◽

...

Keyword(s):

Oral Cancer ◽

Clinical Characteristics ◽

Clinical Stage ◽

The Cancer Genome Atlas ◽

Nucleotide Polymorphisms ◽

Advanced Clinical Stage ◽

Increased Risk ◽

Cancer Genome Atlas ◽

Male Patients ◽

Mrna Binding

Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) is associated with insulin resistance, lipid metabolism, and tumorigenesis. However, the association between the IGF2BP2 polymorphism and oral cancer risk remains unclear. We recruited 1349 male patients with oral cancer and 1198 cancer-free controls. Three single nucleotide polymorphisms IGF2BP2 rs11705701, rs4402960, and rs1470579 were assessed using real-time polymerase chain reaction. The results indicate that the male patients with oral cancer and with the rs11705701 GA+AA, rs4402960 GT+TT, and rs1470579 AC+CC genotypes had increased risk of advanced clinical stage, larger tumor, and progression of lymph node metastasis compared with those with wild-type IGF2BP2. Moreover, according to The Cancer Genome Atlas dataset, high expression of the IGF2BP2 gene is associated with poor survival in patients with head and neck squamous cell carcinoma. In conclusion, our results suggest that IGF2BP2 polymorphisms are associated with less favorable oral cancer clinical characteristics.

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Basal and Luminal Molecular Subtypes in Naturally-Occurring Canine Urothelial Carcinoma are Associated with Tumor Immune Signatures and Dog Breed

Bladder Cancer ◽

10.3233/blc-201523 ◽

2021 ◽

pp. 1-17

Author(s):

Breann C. Sommer ◽

Deepika Dhawan ◽

Audrey Ruple ◽

José A. Ramos-Vara ◽

Noah M. Hahn ◽

...

Keyword(s):

Urothelial Carcinoma ◽

Cancer Progression ◽

Molecular Subtypes ◽

Molecular Subtype ◽

Clinical Stage ◽

Tumor Characteristics ◽

Rna Seq ◽

Advanced Clinical Stage ◽

Naturally Occurring ◽

Immune Signatures

BACKGROUND: Improved therapies are needed for patients with invasive urothelial carcinoma (InvUC). Tailoring treatment to molecular subtypes holds promise, but requires further study, including studies in pre-clinical animal models. Naturally-occurring canine InvUC harbors luminal and basal subtypes, mimicking those observed in humans, and could offer a relevant model for the disease in people. OBJECTIVE: To further validate the canine InvUC model, clinical and tumor characteristics associated with luminal and basal subtypes in dogs were determined, with comparison to findings from humans. METHODS: RNA sequencing (RNA-seq) analyses were performed on 56 canine InvUC tissues and bladder mucosa from four normal dogs. Data were aligned to CanFam 3.1, and differentially expressed genes identified. Data were interrogated with panels of genes defining luminal and basal subtypes, immune signatures, and other tumor features. Subject and tumor characteristics, and outcome data were obtained from medical records. RESULTS: Twenty-nine tumors were classified as luminal and 27 tumors as basal subtype. Basal tumors were strongly associated with immune infiltration (OR 52.22, 95%CI 4.68–582.38, P = 0.001) and cancer progression signatures in RNA-seq analyses, more advanced clinical stage, and earlier onset of distant metastases in exploratory analyses (P = 0.0113). Luminal tumors were strongly associated with breeds at high risk for InvUC (OR 0.06, 95%CI 0.01 –0.37, P = 0.002), non-immune infiltrative signatures, and less advanced clinical stage. CONCLUSIONS: Dogs with InvUC could provide a valuable model for testing new treatment strategies in the context of molecular subtype and immune status, and the search for germline variants impacting InvUC onset and subtype.

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APLN: A potential novel biomarker for cervical cancer

Science Progress ◽

10.1177/00368504211011341 ◽

2021 ◽

Vol 104 (2) ◽

pp. 003685042110113

Author(s):

Yusha Chen ◽

Xiaoqian Lin ◽

Jinwen Zheng ◽

Jiancui Chen ◽

Huifeng Xue ◽

...

Keyword(s):

Cervical Cancer ◽

Cox Regression ◽

Clinical Stage ◽

Mapk Signaling ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

High Expression ◽

Receptor Interaction ◽

Primary Therapy ◽

Advanced Clinical Stage

Apelin (APLN) is recently demonstrated a direct association with many malignant diseases. However, its effects on cervical cancer remain unclear. This study therefore aims to evaluate the association between APLN expression and cervical cancer using publicly available data from The Cancer Genome Atlas (TCGA). The Pearson χ2 test and Fish exact test, as well as logistic regression, were used to evaluate the relationship between clinicopathological factors in cervical cancer and the expression of APLN. Additionally, the Cox regression and Kaplan-Meier methods were conducted to analyze the Overall Survival (OS) of cervical cancer patients in TCGA. Finally, gene set enrichment analysis (GSEA) was performed to establish its biological functions. High expression of APLN in cervical cancer was significantly associated with a more advanced clinical stage (OR = 1.91 (1.21–3.05) for Stage II, Stage III, and Stage IV vs Stage I, p = 0.006). Additionally, it was associated with poor outcome after primary therapy (OR = 2.14 (1.03–4.59) for Progressive Disease (PD), Stable Disease (SD), and Partial Response (PR) vs Complete Remission (CR), p = 0.045) and high histologic grade (OR = 1.67 (1.03–2.72) for G3 and G4 vs G1 and G2, p = 0.037). Moreover, multivariate analysis showed that high expression of APLN was associated with a shorter OS. GSEA demonstrated that six KEGG pathways, including PPAR signaling, ECM-receptor interaction, focal adhesion, MAPK signaling, TGF-beta signaling, and Gap junction pathways were differentially enriched in the high expression APLN phenotype. The recent study suggests that APLN plays an important role in the progression of cervical cancer and might be a promising prognostic biomarker of the disease.

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Expression of protease-activated receptor-2 (PAR-2) is related to advanced clinical stage and adverse prognosis in ovarian clear cell carcinoma

Human Pathology ◽

10.1016/j.humpath.2017.04.008 ◽

2017 ◽

Vol 64 ◽

pp. 156-163 ◽

Cited By ~ 8

Author(s):

Murasaki Aman ◽

Yoshihiro Ohishi ◽

Hiroko Imamura ◽

Tomoko Shinozaki ◽

Nobuko Yasutake ◽

...

Keyword(s):

Cell Carcinoma ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Clinical Stage ◽

Ovarian Clear Cell Carcinoma ◽

Advanced Clinical Stage ◽

Protease Activated Receptor 2

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Perioperative mortality of head and neck cancers

BMC Cancer ◽

10.1186/s12885-021-07998-z ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Yannan Wang ◽

Mengxue Wang ◽

Yan Tang ◽

Bincan Sun ◽

Kai Wang ◽

...

Keyword(s):

Head And Neck Cancer ◽

Head And Neck ◽

Neck Cancer ◽

Cardiopulmonary Arrest ◽

Clinical Stage ◽

Maxillofacial Surgery ◽

Head And Neck Cancers ◽

Oral And Maxillofacial Surgery ◽

Perioperative Mortality ◽

Advanced Clinical Stage

Abstract Background Head and neck cancers are aggressive cancers, most clinical studies focused on the prognosis of patients with head and neck cancer. However, perioperative mortality was rarely mentioned. Methods A retrospective analysis was performed using all head and neck cancer patients admitting in the Department of Oral and Maxillofacial Surgery of the Second Xiangya Hospital, Central South University from January 2010 to December 2019. The analysis of overall survival and progression-free survival were performed using the Kaplan–Meier method, and cross tabulation with chi-squared testing was applied to analyze the difference in parameters between groups. Results From January 2010 to December 2019, a total of 6576 patients with head and neck cancers were admitted to our department and 7 died in the hospital, all of whom were middle-aged and elderly patients including 6 males and 1 female. The perioperative mortality rate (POMR) was about 1‰. The causes of death included acute heart failure, rupture of large blood vessels in the neck, hypoxic ischemic encephalopathy due to asphyxia, respiratory failure and cardiopulmonary arrest. Conclusion Preoperative radiotherapy, previous chemotherapy, hypertension, diabetes, advanced clinical stage and postoperative infection are risk factors for perioperative mortality of head and neck cancer.

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MicroRNA-3666 inhibits lung cancer cell proliferation, migration, and invasiveness by targeting BPTF

Biochemistry and Cell Biology ◽

10.1139/bcb-2018-0301 ◽

2019 ◽

Vol 97 (4) ◽

pp. 415-422 ◽

Cited By ~ 3

Author(s):

Linqing Pan ◽

Zhipeng Tang ◽

Lina Pan ◽

Ranran Tang

Keyword(s):

Lung Cancer ◽

Cell Proliferation ◽

Lung Adenocarcinoma ◽

Signaling Pathways ◽

Histological Grade ◽

Clinical Stage ◽

Luciferase Reporter ◽

Advanced Clinical Stage ◽

Mesenchymal Transition ◽

Adenocarcinoma Cell

A previous study by our group indicted that overexpression of bromodomain PHD-finger transcription factor (BPTF) occurs in lung adenocarcinoma, and is closely associated with advanced clinical stage, higher numbers of metastatic lymph nodes, the occurrence of distant metastasis, low histological grade, and poor prognosis. Down-regulation of BPTF inhibited lung adenocarcinoma cell proliferation and promoted lung adenocarcinoma cell apoptosis. The purpose of this study is to identify valuable microRNAs (miRNAs) that target BPTF to modulate lung adenocarcinoma cell proliferation. In our results, we found that miR-3666 was notably reduced in lung adenocarcinoma tissues and cell lines. Using an miR-3666 mimic, we discovered that cell proliferation, migration, and invasiveness were suppressed by miR-3666 overexpression, but these were all enhanced when the expression of miR-3666 was reduced. Moreover, bioinformatics analysis using the TargetScan database and miRanda software suggested a putative target site in BPTF 3′-UTR. Furthermore, using a luciferase reporter assay, we verified that miR-3666 directly targets the 3′-UTR of BPTF. Using Western blot we discovered that overexpression of miR-3666 negatively regulates the protein expression of BPTF. Finally, we identified that the PI3K–AKT and epilthelial–mesenchymal transition (EMT) signaling pathways were inhibited by miR-3666 overexpression in lung cancer cells. In conclusion, our data indicate that miR-3666 could play an essential role in cell proliferation, migration, and invasiveness by targeting BPTF and partly inhibiting the PI3K–AKT and EMT signaling pathways in human lung cancers.

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Increased STIP1 and Hsp90 Correlate with Progression and Prognosis of Lung Adenocarcinoma

10.21203/rs.3.rs-226260/v1 ◽

2021 ◽

Author(s):

Biaoxue Rong ◽

Youwen Zhang ◽

Junye Wang ◽

Shucheng Ye ◽

Maoqing Guo ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Malignant Tumors ◽

Clinical Stage ◽

A549 Cells ◽

Biological Behavior ◽

Prognostic Indicators ◽

Normal Lung ◽

Clinicopathological Parameters ◽

Strong Positive Correlation ◽

Advanced Clinical Stage

Abstract Background: Stress-inducible phosphoprotein 1 (STIP1) and heat shock protein 90 (Hsp90) have been found to be correlated with malignant tumors. The aim of this investigation was to study the relationship between their expressions and lung adenocarcinoma (LAC). Methods: The expressions of STIP1and Hsp90 in LAC cells and tissues were tested by immunohistochemistry and western blot; the correlation between their expressions and clinicopathological parameters of LAC was analyzed by survival analysisand multiple regression analysis. Results: Expressions of STIP1 and Hsp90 were higher in A549 cells and LAC tissues than that in 16 human bronchial epithelial cells (16HBE cells) (P<0.05) and adjacent normal lung tissues (P < 0.05). The expression of STIP1 and Hsp90 in LAC showed a strong positive correlation (P < 0.05) and significantly correlated with lymph node metastasis (P < 0.05), advanced clinical stage (P < 0.05) and shorter survival (P < 0.05) of LAC. Conclusions: Increased expressions of STIP1 and Hsp90 were closely related to malignant biological behavior of LAC, suggesting that they could be used as potential biomarkers and prognostic indicators for LAC.

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Malignant Extracranial Germ Cell Tumours: A First Report by the South African Children’s Cancer Study Group

10.22541/au.163338814.45716004/v2 ◽

2021 ◽

Author(s):

Marc Hendricks ◽

Annibale Cois ◽

Jennifer Geel ◽

Jan du Plessis ◽

Mairi Bassingthwaighte ◽

...

Keyword(s):

Germ Cell ◽

South African ◽

Economic Status ◽

Clinical Stage ◽

Elevated Serum ◽

Treatment Protocol ◽

Stage Iv ◽

Germ Cell Tumours ◽

Advanced Clinical Stage ◽

Risk Of Death

OBJECTIVE To determine the overall survival (OS) and prognostic factors influencing outcomes in children and adolescents with malignant extracranial germ cell tumours (MEGCTs) in preparation for the development of a harmonised national treatment protocol.METHODS A retrospective folder review was undertaken at nine South African paediatric oncology units to document patient profiles, tumour and treatment-related data and outcomes for all children with biopsy proven MEGCTs from birth up to and including 16 years of age. RESULTS Between 1 January 2000 and 31 December 2015, 218 patients were diagnosed with MEGCTs. Female sex (HR 0.284 p=0.037) and higher socio-economic status (SES) (HR 0.071; p=0.039) were associated with a significantly lower risk of death. Advanced clinical stage at diagnosis significantly affected 5-year OS: stage I -96%; stage II - 94.3%; stage III -75.5%; (p=0.017) and stage IV (60.1%; p<0.001). There was a significant association between earlier stage at presentation and higher SES (p=0.03). Patients with a serum AFP level of more than 33,000 ng/ml at diagnosis had significantly poorer outcomes (p=0.002). The use of chemotherapy significantly improved survival, irrespective of the regimen used (p<0.001). CONCLUSIONS The cohort demonstrated a 5-year OS of 80.3% with an EFS of 75.3%. Stage, the use of chemotherapy and an elevated serum AFP level of more than 33,000ng/ml were independently predictive of outcome. The relationship between SES and outcome is important as the implementation of the new national protocol hopes to standardise care across the socio-economic divide.

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