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1.
Mol Carcinog ; 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38860607

ABSTRACT

BACKGROUND: Pyroptosis has been implicated in the advancement of various cancers. Triggering pyroptosis within tumors amplifies the immune response, thereby fostering an antitumor immune environment. Nonetheless, few published studies have evaluated associations between functional variants in the pyroptosis-related genes and clinical outcomes of patients with non-oropharyngeal head and neck squamous cell carcinoma (NON-ORO HNSCC). METHODS: We conducted an association study of 985 NON-ORO HNSCC patients who were randomly divided into two groups: the discovery group of 492 patients and the replication group of 493 patients. We used Cox proportional hazards regression analysis to examine associations between genetic variants of the pyroptosis-related genes and survival of patients with NON-ORO HNSCC. Bayesian false discovery probability (BFDP) was used for multiple testing correction. Functional annotation was applied to the identified survival-associated genetic variants. RESULTS: There are 8254 single-nucleotide polymorphisms (SNPs) located in 82 pyroptosis-related genes, of which 202 SNPs passed multiple testing correction with BFDP < 0.8 in the discovery and six SNPs retained statistically significant in the replication. In subsequent stepwise multivariable Cox regression analysis, two independent SNPs (CHMP4A rs1997996 G > A and PANX1 rs56175344 C > G) remained significant with an adjusted hazard ratios (HR) of 1.31 (95% confidence interval [CI] = 1.09-1.57, p = 0.004) and 0.65 (95% CI = 0.51-0.83, p = 0.0005) for overall survival (OS), respectively. Further analysis of the combined genotypes revealed progressively worse OS associated with the number of unfavorable genotypes (ptrend < 0.0001 and 0.021 for OS and disease-specific survival, respectively). Moreover, both PANX1 rs56175344G and CHMP4A rs1997996A alleles were correlated with reduced mRNA expression levels. CONCLUSIONS: Genetic variants in the pyroptosis pathway genes may predict the survival of NON-ORO HNSCC patients, likely by reducing the gene expression, but our findings need to be replicated by larger studies.

2.
J Oncol ; 2020: 7042025, 2020.
Article in English | MEDLINE | ID: mdl-33014054

ABSTRACT

IL24 mRNA is known to have an apoptotic effect on cancer cells but not on noncancer cells. However, the expression level of the IL24 mRNA in head and neck squamous cell carcinoma (HNSCC) and its subgroups is rarely studied. In this study, the clinical implication of IL24 mRNA was evaluated in the common subgroups of HNSCC, including oral squamous cell carcinoma (OSCC), nasopharyngeal carcinoma (NPC), and laryngeal squamous cell carcinoma (LSCC) for analysis. Substantial IL24 mRNA expression data were calculated from several databases, such as the Gene Expression Omnibus (GEO), ArrayExpress, Sequence Read Archive (SRA), ONCOMINE, and The Cancer Genome Atlas (TCGA) databases. We ultimately collected a total of 41 microarrays and RNA-seq including 1,564 HNSCC and 603 noncancer tissue samples. IL24 mRNA was highly expressed in OSCC, LSCC, and NPC as shown by the separated standard mean difference (SMD), as well as HNSCC as a whole part (SMD = 1.47, 95% confdence interval (CI) = 1.24-1.70, P < 0.0001). In all subgroups, the IL24 mRNA upregulation had the ability to distinguish cancer from noncancer tissue with area under the curves (AUCs) of the summary receiver operating characteristic (sROC) higher than 0.85. In conclusion, IL24 mRNA may be used as a potential marker for cancer screening, and its clinical diagnostic value needs to be further studied. It also provides a new idea for the treatment of the IL24 gene in HNSCC and its subgroups in the future.

3.
World J Surg Oncol ; 18(1): 240, 2020 Sep 05.
Article in English | MEDLINE | ID: mdl-32891152

ABSTRACT

BACKGROUND: Thyroid cancer (TC) is the most common endocrine malignancy; basigin (also known as BSG) plays a crucial role in tumor cell invasion, metastasis, and angiogenesis. This study was designed to identify the change of BSG expression in TC and its possible potential mechanism. METHODS: The BSG expression levels in TC were demonstrated using data collected from in-house immunohistochemical (IHC), RNA-sequencing (RNA-seq), microarrays, and literatures. Integrated analysis was performed to determined BSG expression levels in TC comprehensively. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed with the integration of BSG co-expressed genes and differentially expressed genes (DEGs) in TC tissues to explore the potential mechanisms of BSG in TC. RESULTS: The protein expression level of BSG was significantly higher in TC cases based on the IHC experiments. In addition, the combined SMD for BSG expression was 0.39 (p < 0.0001), the diagnostic odds ratio was 3.69, and the AUC of the sROC curve was 0.6986 using 1182 TC cases and 437 non-cancerous cases from 17 independent datasets. Furthermore, BSG co-expressed genes tended to be enriched in gene terms of the extracellular matrix (ECM), cell adhesion, and cell-cell interactions. The expression levels of nine hub BSG co-expressed genes were markedly upregulated in TC cases. CONCLUSION: BSG expression levels were closely correlated with the progression of TC and may affect the signals of the ECM, cell adhesion, and cell-cell interactions.


Subject(s)
Basigin , Thyroid Neoplasms , Gene Expression Regulation, Neoplastic , Gene Ontology , Humans , Prognosis , Thyroid Neoplasms/genetics
4.
Cancer Biomark ; 29(1): 111-124, 2020.
Article in English | MEDLINE | ID: mdl-32623386

ABSTRACT

Interleukin 24 (IL24) has been documented to be highly expressed in several cancers, but its role in laryngeal squamous cell carcinoma (LSCC) remains unclarified. In this study, to reveal the function and its clinical significance of IL24 in LSCC, multiple detecting methods were used comprehensively. IL24 protein expression was remarkably higher in LSCC (n= 49) than non-cancerous laryngeal controls (n= 26) as detected by in-house immunohistochemistry. Meanwhile, the IL24 mRNA expression was also evaluated based on high throughput data from Gene Expression Omnibus, The Cancer Genome Atlas, ArrayExpress and Oncomine databases. Consistently with the protein level, IL24 mRNA expression level was also predominantly upregulated in LSCC (n= 172) compared to non-cancerous laryngeal tissues (n= 81) with the standard mean difference (SMD) being 1.25 and the area under the curve (AUC) of the summary receiver operating characteristic (sROC) being 0.89 (95% CI = 0.86-0.92). Furthermore, the related genes of IL24 and the differentially expressed genes (DEGs) of LSCC were intersected and sent for Gene ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and the protein-protein interaction (PPI) analyses. In the GO annotation, the top terms of biological process (BP), cellular component (CC) and molecular function (MF) were extracellular matrix organization, extracellular matrix, cytokine activity, respectively. The top pathway of KEGG was ECM-receptor interaction. The PPI networks indicated the top hub genes of IL24-related genes in LSCC were SERPINE1, TGFB1, MMP1, MMP3, CSF2, and ITGA5. In conclusion, upregulating expression of IL24 may enhance the occurrence of LSCC, which owns prospect diagnostic ability and therapeutic significance in LSCC.


Subject(s)
Biomarkers, Tumor/genetics , Carcinoma, Squamous Cell/genetics , Interleukins/genetics , Squamous Cell Carcinoma of Head and Neck/genetics , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/pathology , Computational Biology , Female , Gene Expression Regulation, Neoplastic/genetics , Gene Regulatory Networks/genetics , Granulocyte-Macrophage Colony-Stimulating Factor/genetics , Humans , Integrins/genetics , Male , Matrix Metalloproteinase 1/genetics , Matrix Metalloproteinase 3/genetics , MicroRNAs , Middle Aged , Plasminogen Activator Inhibitor 1/genetics , Protein Interaction Maps/genetics , Signal Transduction/genetics , Squamous Cell Carcinoma of Head and Neck/diagnosis , Squamous Cell Carcinoma of Head and Neck/pathology , Squamous Cell Carcinoma of Head and Neck/therapy , Transforming Growth Factor beta1/genetics
5.
Med Sci Monit ; 26: e922854, 2020 Jun 12.
Article in English | MEDLINE | ID: mdl-32529991

ABSTRACT

BACKGROUND Oral squamous cell carcinoma (OSCC) is the sixth most prevalent cancer worldwide, with low 5-year survival rate. To identify novel prognostic markers for OSCC and determine the immune and stromal landscape of OSCC, a risk signature for OSCC patients was constructed in this study. MATERIAL AND METHODS Immune and stromal scores for OSCC samples from the Genomic Data Commons Data Portal were computed to delineate the tumor microenvironment landscape of oral cancer based on the Estimation of STromal and Immune cells in MAlignant Tumours using Expression data algorithm. An immune score-based risk signature was constructed by combining random forest and support vector machine methods. Correlation analysis of risk signature gene expression and immune cell infiltration was conducted, and the distinguishing power of individual signature genes was evaluated by analyzing receiver operating characteristics (ROC) curves. Differentially enriched pathways between high and low risk groups were investigated via gene set variation analysis. ROC curves were plotted for signature genes to examine their ability to distinguish the recurrence and survival status of OSCC patients from GSE84846. RESULTS An immune score-related risk signature composed of ARMH1, F2RL2, AC004687.1, COL6A5, AC008750.1, RAB19, CRLF2, GRIP2, and FAM162B performed well in the prognostic stratification of OSCC patients and could effectively distinguish their survival status. Lists of pathways, including cytokine-cytokine receptor interaction and cell adhesion molecules displayed remarkable differential enrichment between high and low risk OSCC patients. CONCLUSIONS An immune score-based risk signature constructed presently may be useful to decide appropriate treatment options for individual OSCC patients.


Subject(s)
Mouth Neoplasms/genetics , Mouth Neoplasms/immunology , Squamous Cell Carcinoma of Head and Neck/genetics , Squamous Cell Carcinoma of Head and Neck/immunology , Cytokines/genetics , Cytokines/immunology , Databases, Genetic , Female , Gene Expression Profiling , Humans , Immune System/cytology , Immune System/immunology , Lymphocytes, Tumor-Infiltrating , Male , Multivariate Analysis , Prognosis , Proportional Hazards Models , Protein Interaction Maps , RNA, Messenger , RNA-Seq , ROC Curve , Receptors, Cytokine/genetics , Receptors, Cytokine/immunology , Risk Assessment , Support Vector Machine , Transcriptome , Tumor Microenvironment/genetics , Tumor Microenvironment/immunology
6.
Comput Biol Chem ; 86: 107258, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32304977

ABSTRACT

BACKGROUND: Thyroid carcinoma (THCA) is one of the most frequent endocrine cancers and has increasing morbidity. Annexin A2 (ANXA2) has been found to be highly expressed in various cancers; however, its expression level and potential mechanism in THCA remain unknown. This study investigated the clinicopathological value and primary molecular machinery of ANXA2 in THCA. MATERIAL AND METHODS: Public RNA-sequencing and microarray data were obtained and analyzed with ANXA2 expression in THCA and corresponding non-cancerous thyroid tissue. A Pearson correlation coefficient calculation was used for the acquisition of ANXA2 coexpressed genes, while edgR, limma, and Robust Rank Aggregation were employed for differentially expressed gene (DEG) in THCA. The probable mechanism of ANXA2 in THCA was predicted by gene ontology and pathway enrichment. A dual-luciferase reporter assay was employed to confirm the targeting relationships between ANXA2 and its predicted microRNA (miRNA). RESULTS: Expression of ANXA2 was significantly upregulated in THCA tissues with a summarized standardized mean difference of 1.09 (P < 0.0001) based on 992 THCA cases and 589 cases of normal thyroid tissue. Expression of ANXA2 was related to pathologic stage. Subsequently, 1442 genes were obtained when overlapping 4542 ANXA2 coexpressed genes with 2248 DEGs in THCA; these genes were mostly enriched in pathways of extracellular matrix-receptor interaction, cell adhesion molecules, and complement and coagulation cascades. MiR-23b-3p was confirmed to target ANXA2 by dual-luciferase reporter assay. CONCLUSIONS: Upregulated expression of ANXA2 may promote the malignant biological behavior of THCA by affecting the involving pathways or being targeted by miR-23b-3p.


Subject(s)
Annexin A2/genetics , Thyroid Neoplasms/genetics , Gene Ontology , Humans , MicroRNAs , Sequence Analysis, RNA , Thyroid Gland/metabolism , Thyroid Gland/pathology , Thyroid Neoplasms/pathology , Up-Regulation
7.
J Cell Physiol ; 235(3): 2403-2413, 2020 03.
Article in English | MEDLINE | ID: mdl-31556116

ABSTRACT

Papillary thyroid carcinoma (PTC) is recognized as one of the most prevalent types of thyroid cancer with poor prognosis. Long noncoding RNA (lncRNA) has undergone an intensive study for their involvement in tumor treatment. This study intends to unravel the association of lncRNA SLC26A4-AS1 with PTC. Initially, PTC-related expression profiling data (GSE33630) was utilized to screen differentially expressed lncRNAs in PTC and the underlying mechanisms involved with the mitogen-activated protein kinase (MAPK) pathway. Moreover, PTC tumor tissues and paracancerous tissues were arranged to determine expressions of TP53, SLC26A4-AS1, and genes related to epithelial-mesenchymal transition (EMT) and the MAPK pathway. Furthermore, SLC26A4-AS1 was overexpressed or underexpressed and JNK was underexpressed through cell transfection to examine the effect of SLC26A4-AS1 on PTC via MAPK pathway. Besides, tumor formation in nude mice was used to verify the fore experiment. LncRNA SLC26A4-AS1 regulating TP53 had the potential to participate in PTC by regulating the MAPK pathway. SLC26A4-AS1 was expressed poorly in PTC. Notably, SLC26A4-AS1 elevated E-cadherin expression while it reduced that of ERK and Vimentin. In addition, the overexpression of SLC26A4-AS1 inactivated the MAPK pathway by promoting TP53 and decreased cell migration, proliferation, and invasion. In addition to all these effects, the overexpression of SLC26A4-AS1 promoted apoptosis of TPC-1 cells. Additionally, the overexpression of lncRNA SLC26A4-AS1 reduced xenograft tumor volume in nude mice. Furthermore, the effect of SLC26A4-AS1 overexpression was found to be promoted after the MAPK pathway inactivation. Taken together, the overexpression of lncRNA SLC26A4-AS1 coffered anti-oncogenic effects on PTC through the inactivation of the MAPK pathway.


Subject(s)
Cell Proliferation/genetics , RNA, Long Noncoding/genetics , Sulfate Transporters/genetics , Thyroid Cancer, Papillary/genetics , Animals , Apoptosis/genetics , Cadherins/genetics , Cell Movement/genetics , Epithelial-Mesenchymal Transition/genetics , Gene Expression Regulation, Neoplastic/genetics , Heterografts , Humans , MAP Kinase Signaling System/genetics , Mice , Thyroid Cancer, Papillary/pathology
8.
J Cell Physiol ; 235(3): 2492-2505, 2020 03.
Article in English | MEDLINE | ID: mdl-31565805

ABSTRACT

Although papillary thyroid carcinoma (PTC) has a favorable prognosis after surgical or medical treatment, its survival rate is still very low. Therefore, finding more reliable therapy methods to limit PTC is a necessity. Compelling evidence has implicated the role of microRNAs (miRNAs or miRs) in PTC. This study aims at investigating the possible effect of microRNA-599 (miR-599) on proliferation, apoptosis, and epithelial-mesenchymal transition (EMT) of PTC cells by targeting Hey2 gene. Differentially expressed genes/miRNAs associated with PTC were screened based on microarray analysis. Then, the expression of the candidate gene, as well as, the regulatory miRNA were detected in PTC cells, the related signaling pathway was verified. Afterward, the relationship between the miR and the candidate gene was verified by dual-luciferase reporter gene assay. Subsequently, the effects of overexpressed miR and silenced candidate gene on cell proliferation, cell apoptosis, EMT, migration, and invasion were detected. In PTC tissues and cells, miR-599 was downregulated while Hey2 expressed highly. Hey2 is a target gene of miR-559. In addition, the expression of Bax and E-cadherin was elevated while that of Hey2, Notch1, Delta-like1, Hes1, N1ICD, Jagged1, Snail, Slug, N-cadherin and Vimentin, and Bcl-2 was reduced in cells treated with upregulated miR-599 or downregulated Hey2. Moreover, miR-599 overexpression or Hey2 silencing inhibited cell proliferation, migration, invasion, along with EMT but promoted apoptosis. This study verified that miR-599 promotes apoptosis and represses proliferation, EMT of PTC cells through inactivating the Notch signaling pathway by downregulating Hey2, which has great clinical significance for PTC treatment.


Subject(s)
Basic Helix-Loop-Helix Transcription Factors/genetics , Cell Proliferation/genetics , MicroRNAs/genetics , Repressor Proteins/genetics , Thyroid Cancer, Papillary/genetics , Adult , Apoptosis/genetics , Cell Line, Tumor , Cell Movement/genetics , Epithelial-Mesenchymal Transition/genetics , Female , Gene Expression Regulation, Neoplastic/genetics , Humans , Male , Middle Aged , Receptors, Notch/genetics , Signal Transduction/genetics , Survival Rate , Thyroid Cancer, Papillary/pathology
9.
Gene ; 704: 142-148, 2019 Jul 01.
Article in English | MEDLINE | ID: mdl-30965127

ABSTRACT

Thyroid cancer is the most common type of endocrine tumor. The TNM classification remains a standard for treatment determination and predicting prognosis in thyroid cancer. The genes modules associated with the progression of papillary thyroid carcinoma (PTC) were not clear. We applied a weighted gene co-expression network analysis (WGCNA) and differential expression analysis to systematically identified co-expressed gene modules and hub genes associated with PTC progression based on The Cancer Genome Atlas (TCGA) PTC transcriptome sequencing data. An independent validation cohort, GSE27155, was used to evaluate the preservation of gene modules. We identified two co-expressed genes modules associated with progression of PTC. Enrichment analysis indicated that the two modules were enriched in angiogenesis and extracellular matrix organization. DCN, COL1A1, COL1A2, COL5A2 and COL3A1 were hub genes in the co-expressed network. We systematically identified co-expressed gene modules and hub genes associated with PTC progression for the first time, which provided insights into the mechanisms underlying PTC progression and some potential targets for the treatment of PTC.


Subject(s)
Gene Regulatory Networks , Thyroid Cancer, Papillary/genetics , Thyroid Cancer, Papillary/pathology , Thyroid Neoplasms/genetics , Thyroid Neoplasms/pathology , Disease Progression , Female , Gene Expression Profiling/methods , Gene Expression Regulation, Neoplastic , Genetic Predisposition to Disease , High-Throughput Screening Assays , Humans , Male , Neoplasm Staging , Prognosis , Risk Factors , Thyroid Cancer, Papillary/diagnosis , Thyroid Neoplasms/diagnosis
10.
Oncotarget ; 8(46): 81186-81194, 2017 Oct 06.
Article in English | MEDLINE | ID: mdl-29113378

ABSTRACT

D-dimer, one of the canonical markers of hypercoagulability, was reported to be a potential prognostic marker of colorectal cancer. However, an inconsistent conclusion existed in several published studies. Thus, we performed this meta-analysis to provide a comprehensive insight into the prognostic role for pretreatment D-dimer in colorectal cancer. Six databases (English: Pubmed, Embase and Web of Science; Chinese: CNKI, Wangfang and VIP) were utilized for the literature retrieval. Hazard ratio (HR) was pooled by Stata 12.0. A total of fifteen studies (2283 cases) corresponded to this meta-analysis and provided available data to evaluate the prognostic role of D-dimer for colorectal cancer. The pooled HR reached 2.167 (95%. CI (confidence interval): 1.672-2.809, P < 0.001) utilizing random effect model due to obvious heterogeneity among the included studies (I2: 73.3%; P < 0.001). To explore the heterogeneity among the studies, we conducted a sensitivity analysis and found a heterogeneous study. After removing it, the heterogeneity reduced substantially (I2: 0%; P = 0.549) and we obtained a more convincing result by fixed effect model (HR = 2.143, 95% CI = 1.922-2.390, P < 0.001, 14 studies with 2179 cases). In summary, high pretreatment plasma D-dimer predicts poor survival of colorectal cancer based on the current evidence. Further prospective researches are necessary to confirm the role of D-dimer in colorectal cancer.

11.
Asian Pac J Cancer Prev ; 15(11): 4563-6, 2014.
Article in English | MEDLINE | ID: mdl-24969885

ABSTRACT

BACKGROUND: To evaluate relationship between the cyclooxygenase-2 promoter 765G/C polymorphism and digestive cancer risk in China. MATERIALS AND METHODS: A literature search through February 2014 was performed using PubMed, Chinese Biomedical Literature Database (CBM) and China National Knowledge Infrastructure (CNKI) databases, and a meta-analysis was performed with RevMan 5.2 software for odds ratios and 95%CIs. RESULTS: In total, 9 articles with 3,263 cases and 4,858 controls were included in this meta-analysis.The pooled OR (95%CIs) in the co-dominant model (GC vs GG) was 1.56 [1.19, 2.06], and in the dominant model ((CC+GC) vs GG), the pooled OR was 1.59 [1.21, 2.09] in overall cancers. In the subgroup analysis, stratified by cancer type, significant associations were found that the-765C allele had increased pancreatic cancer and gastric risk. No significant liver cancer and colorectal cancer risk of COX-2 -765G/C polymorphism was found. CONCLUSIONS: These findings suggest that COX-2-765*C is related to cancer susceptibility and may increase gastric and pancreatic cancer risk.


Subject(s)
Asian People/genetics , Cyclooxygenase 2/genetics , Digestive System Neoplasms/etiology , Digestive System Neoplasms/genetics , Genetic Predisposition to Disease/genetics , Polymorphism, Genetic/genetics , Promoter Regions, Genetic/genetics , Alleles , Case-Control Studies , Digestive System Neoplasms/pathology , Gastrointestinal Tract/pathology , Humans , Risk , Risk Factors
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