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Caspase-3 expression in tumorigenesis and prognosis of buccal mucosa squamous cell carcinoma.

ABSTRACT: Buccal mucosa squamous cell carcinoma (BMSCC) is the most common oral cancer in Southeast Asia. Caspase-3, a key molecule in regulating apoptosis, promotes the malignancy of various cancers. However, its role in BMSCC is unknown. Herein, we evaluated the association of caspase-3 expression with tumorigenesis and prognosis in BMSCC patients. Immunohistochemical staining indicated that the expression levels of cleaved caspase-3 (p<0.001) and caspase-3 (p<0.001) in 185 BMSCC tissues were significantly higher compared to those in the tumor adjacent normal tissues. Moreover, the high expression of caspase-3 was associated with poor pathological outcomes [advanced pathological stage (p=0.029) and larger tumor size (p=0.002)] and poor disease-free survival in patients receiving postoperative radiotherapy (p=0.030). Moreover, the low co-expression of cleaved caspase-3 and caspase-3 was associated with better disease-specific survival in patients with early pathological stage (I + II, p=0.018) or without lymph node invasion (p=0.043) compared to the positive/high expression of either or both cleaved caspase-3 and caspase-3. Taken together, cleaved caspase-3 and caspase-3 could be biomarkers for tumorigenesis in BMSCC patients. Cleaved caspase-3 and/or caspase-3 might be prognostic biomarkers for certain stages of BMSCC.

SUBMITTER: Huang JS

PROVIDER: S-EPMC5663591 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Caspase-3 expression in tumorigenesis and prognosis of buccal mucosa squamous cell carcinoma.

Huang Jer-Shyung JS Yang Cheng-Mei CM Wang Jyh-Seng JS Liou Huei-Han HH Hsieh I-Chien IC Li Guan-Cheng GC Huang Sin-Jhih SJ Shu Chih-Wen CW Fu Ting-Ying TY Lin Yun-Chung YC Ger Luo-Ping LP Liu Pei-Feng PF

Oncotarget 20170824 48

Buccal mucosa squamous cell carcinoma (BMSCC) is the most common oral cancer in Southeast Asia. Caspase-3, a key molecule in regulating apoptosis, promotes the malignancy of various cancers. However, its role in BMSCC is unknown. Herein, we evaluated the association of caspase-3 expression with tumorigenesis and prognosis in BMSCC patients. Immunohistochemical staining indicated that the expression levels of cleaved caspase-3 (<i>p</i><0.001) and caspase-3 (<i>p</i><0.001) in 185 BMSCC tissues w ...[more]

PMID: 29137419

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Project description:ObjectiveOral tongue squamous cell carcinoma (OTSCC) and buccal squamous cell carcinoma (BSCC) are the first and second leading causes of oral cancer, respectively. OTSCC and BSCC are associated with poor prognosis in patients with oral cancer. Thus, we aimed to indicate signaling pathways, Gene Ontology terms, and prognostic markers mediating the malignant transformation of the normal oral tissue to OTSCC and BSCC.MethodsThe dataset GSE168227 was downloaded and reanalyzed from the GEO database. Orthogonal partial least square (OPLS) analysis identified common differentially expressed miRNAs (DEMs) in OTSCC and BSCC compared to their adjacent normal mucosa. Next, validated targets of DEMs were identified using the TarBase web server. With the use of the STRING database, a protein interaction map (PIM) was created. Using the Cytoscape program, hub genes and clusters within the PIM were shown. Next, gene-set enrichment analysis was carried out using the g:Profiler tool. Using the GEPIA2 web tool, analyses of gene expression and survival analysis were also performed.ResultsTwo DEMs, including has-miR-136 and has-miR-377, were common in OTSCC and BSCC (p value <0.01; |Log2 FC| > 1). A total of 976 targets were indicated for common DEMs. PIM included 96 hubs, and the upregulation of EIF2S1, CAV1, RAN, ANXA5, CYCS, CFL1, MYC, HSP90AA1, PKM, and HSPA5 was significantly associated with a poor prognosis in the head and neck squamous cell carcinoma (HNSCC), while NTRK2, HNRNPH1, DDX17, and WDR82 overexpression was significantly linked to favorable prognosis in the patients with HNSCC. "Clathrin-mediated endocytosis" was considerably dysregulated in OTSCC and BSCC.ConclusionThe present study suggests that has-miR-136 and has-miR-377 are underexpressed in OTSCC and BSCC than in normal oral mucosa. Moreover, EIF2S1, CAV1, RAN, ANXA5, CYCS, CFL1, MYC, HSP90AA1, PKM, HSPA5, NTRK2, HNRNPH1, DDX17, and WDR82 demonstrated prognostic markers in HNSCC. These findings may benefit the prognosis and management of individuals with OTSCC/BSCC. However, additional experimental verification is required.

Dataset Information

Caspase-3 expression in tumorigenesis and prognosis of buccal mucosa squamous cell carcinoma.

Publications

Caspase-3 expression in tumorigenesis and prognosis of buccal mucosa squamous cell carcinoma.

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