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1.
Artigo em Inglês | MEDLINE | ID: mdl-38956906

RESUMO

BACKGROUND: Sodium voltage-gated channel beta subunit 4 (SCN4B) plays a suppressive role in various tumors. However, the role of SCN4B in non-small cell lung cancer (NSCLC) is not yet clear. This study aims to investigate the expression of SCN4B in NSCLC patients and its correlation with prognosis. METHODS: Firstly, the expression of SCN4B in non-small cell lung cancer (NSCLC) was analyzed using The Cancer Genome Atlas (TCGA) database. Then, differential expression genes (DEGs) were identified using R software. Next, DEG enrichment pathways were analyzed using the R package clusterProfiler. Protein-protein interaction networks were revealed through STRING analysis. A heatmap showed significant differential expression of SCN4B. Further analysis included examining SCN4B expression in a pan-cancer context and its correlation with 24 types of immune cells in NSCLC. Subsequently, quantitative real-time polymerase chain reaction (qRT-PCR), Western Blot, immunohistochemistry, and clinical data were used to validate SCN4B expression and prognostic value in NSCLC patients. RESULTS: SCN4B mRNA expression in non-small cell lung cancer tissues was significantly lower than in adjacent normal tissues (p < 0.001). Clinical correlation analysis confirmed its association with clinical pathology. Gene set enrichment analysis (GSEA) and tumor immune-related analyses indicated that SCN4B is involved in NSCLC-related Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and participates in immune infiltration. qRT-PCR, Western Blot, and immunohistochemistry also confirmed that SCN4B is downregulated in NSCLC patients and is associated with poor prognosis. CONCLUSION: SCN4B is downregulated in tumor tissues of NSCLC patients and is associated with a poor prognosis.

2.
Mol Biotechnol ; 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38676754

RESUMO

Maternal embryonic leucine zipper kinase (MELK) is an oncogene in many tumors, although its contribution to lung adenocarcinoma (LUAD) is unclear. We examined MELK expression in patient LUAD tissue and matched healthy lung tissues. We investigated the connection between MELK expression and tumor differentiation, lymph node metastasis, and patient survival. We downregulated MELK expression using small-hairpin RNA to assess its impact on LUAD cell proliferation, clonogenicity, and invasion. We also investigated the molecular mechanism underlying these effects. MELK expression was significantly heightened in LUAD tissue as opposed to the matching healthy lung tissues. LUAD patients who had MELK overexpression had a worse prognosis. Suppression of MELK hinders proliferation, clonogenicity, and invasion of LUAD cells. The MELK suppression led to the arrest of the cell cycle's G1/S phase by reducing the cyclin E1 and cyclin D expression. Our outcomes manifest that MELK can function as a beneficial prognostic indication and a new therapy target for LUAD. MELK has an essential function in progressing LUAD, manifesting potential as a viable target for therapeutic intervention in this disease management.

3.
Mediators Inflamm ; 2023: 2763168, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37197572

RESUMO

WD-repeat protein 72(WDR72; OMIM∗613214), a scaffolding protein lacking intrinsic enzymatic activity, produces numerous ß-propeller blade formations, serves as a binding platform to assemble protein complexes and is critical for cell growth, differentiation, adhesion, and migration. Despite evidence supporting a basic role of WDR72 in the tumorigenesis of particular cancers, the value of WDR72 in non-small-cell lung cancer (NSCLC), the tumor with the highest mortality rate globally, is undocumented. We investigated the prognostic value of WDR72 in NSCLC and studied its potential immune function and its correlation with ferroptosis. According to The Cancer Genome Atlas, Cancer Cell Line Encyclopedia, Genotype-Tissue Expression, and Gene Set Cancer Analysis, we used multiple bioinformatic strategies to investigate the possible oncogenic role of WDR72, analyze WDR72 and prognosis, and immune cell infiltration in different tumors correlation. WDR72 exhibited a high expression in NSCLC and a positive association with prognosis. WDR72 expression was related to immune cell infiltration and tumor immune microenvironment in NSCLC. Finally, we validated WDR72 in human NSCLC; it has a predictive value in NSCLC related to its function in tumor progression and immunity. The significance of our study is that WDR72 can be used as a potential indicator of lung cancer prognosis. Helping physicians more accurately predict patient survival and risk of disease progression.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Prognóstico , Proteínas/metabolismo , Biomarcadores , Microambiente Tumoral
4.
Front Oncol ; 13: 1015358, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37035142

RESUMO

Background: It has been established that the scavenger receptor class A member 5 (SCARA5) functions as a tumor suppressor gene in various cancer types. To our knowledge, no comprehensive study has hitherto investigated the expression and function of SCARA5 in melanoma. This study aimed to determine the association between SCARA5 and melanoma. Methods: Analysis of SCARA5 mRNA expression was performed using The Cancer Genome Atlas (TCGA) data sets. To evaluate the clinical significance of SCARA5, the clinical data of 93 patients with melanoma were collected. The role of SCARA5 expression in prognosis was also analyzed. In this study, survival was evaluated by Kaplan-Meier analysis and compared using the log-rank test. Univariate and multivariate Cox proportional hazard regression analyses were used to identify independent predictors. The Kyoto Encyclopedia of Genes and Genomes, Gene Ontology, and gene set enrichment analysis (GSEA) were used to perform gene set functional annotations. Protein-protein interaction (PPI) networks were constructed to illustrate gene-gene interactions. The Tumor IMmune Estimation Resource (TIMER) database was used to explore the association between SCARA5 and immune infiltration levels. Results: The results showed that the SCARA5 mRNA expression in melanoma was significantly lower than in adjacent normal skin tissue (p < 0.001). Moreover, decreased expression of SCARA5 in melanoma correlated with the tumor, node, and metastasis (TNM) stage and recurrence (p < 0.05). The overall survival (OS) was significantly higher in melanoma with high SCARA5 expression compared with low SCARA5 expression (p < 0.001). During univariate analysis, SCARA5 expression, tumor (T) stage, node (N) stage, metastasis (M) stage, and recurrence correlated with OS (p < 0.05). Further multivariate Cox regression analysis showed that SCARA5 expression (p = 0.012) could be an independent prognostic factor for OS in cutaneous malignant melanoma. GSEA analysis showed that SCARA5 was significantly enriched in various pathways, such as response to developmental biology and response to antimicrobial peptides. Correlation analysis showed a positive correlation with CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells (p < 0.05), and a negative correlation with tumor purity (p < 0.05). Conclusion: SCARA5 has significant potential as a prognostic biomarker and as a promising therapeutic target in melanoma. Furthermore, SCARA5 expression in melanoma is related to the level of immune infiltration.

5.
Front Neurol ; 13: 959531, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36158955

RESUMO

Vulnerable carotid plaque is closely related to the occurrence of Ischemic stroke. Therefore, accurate and rapid identification of the nature of carotid plaques is essential. AS is a chronic immune inflammatory process. Systemic immune-inflammation index (SII) is a novel index of immune inflammation obtained from routine whole blood cell count analysis, which comprehensively reflects the state of inflammation and immune balance in the body. This study sought to explore the relationship between SII level and carotid plaque vulnerability, plaque composition characteristics, and acute ischemic stroke (AIS) severity. A total of 131 patients diagnosed with AIS presenting with a carotid atherosclerotic plaque were enrolled in this study. Using carotid ultrasound (CDU) to assess the carotid-responsible plaque properties, we divided the patients into stable plaques group and vulnerable plaques group, and analyzed the correlation between SII levels and plaque vulnerability. And we further analyzed to evaluate the correlation between high SII levels and plaque characteristics and AIS severity. In addition, Cohen's Kappa statistics was used to detect the consistency of Carotid ultrasound (US) and cervical High-resolution magnetic resonance imaging (HRMRI) in evaluating plaque vulnerability. The findings showed that the vulnerable group had higher levels of SII compared with the stable group. The high SII group had more vulnerable plaques and a high frequency of plaque fibrous cap rupture compared with the low SII group. Logistic analysis showed that a high SII level was an independent risk factor for vulnerable plaques (odds ratio [OR] = 2.242) and plaque fibrous cap rupture (OR=3.462). The results also showed a high consistency between Carotid US and HRMRI methods in the assessment of plaque vulnerability [Cohen's kappa value was 0.89 (95% CI = 0.78-0.97)] and the level of SII was positively associated with NIHSS score (r = 0.473, P < 0.001). Our study suggests that elevated levels of SII may have adverse effects on the vulnerability of carotid plaques, especially in stroke patients with vulnerable plaques with ruptured fibrous caps, which may aggravate the severity of AIS.

6.
J Immunol Res ; 2022: 1161931, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35600043

RESUMO

Background: Globally, non-small-cell lung cancer (NSCLC) is one of the most prevalent tumors. Various studies have investigated its etiology, but the molecular mechanism of NSCLC has not been elucidated. Methods: The GSE19804, GSE118370, GSE19188, GSE27262, and GSE33532 microarray datasets were obtained from the Gene Expression Omnibus (GEO) database for the identification of genes involved in NSCLC development as well as progression. Then, the identified differentially expressed genes (DEGs) were subjected to functional enrichment analyses. The protein-protein interaction (PPI) network was built after which module analysis was conducted via the Search Tool for Retrieval of Interacting Genes/Proteins (STRING) and Cytoscape. There were 562 DEGs: 98 downregulated genes and 464 upregulated. These DEGs were established to be enriched in p53 signaling pathway, transendothelial leukocyte migration, cell adhesion molecules, contractions of vascular smooth muscles, coagulation and complement cascades, and axon guidance. Assessment of tumor immunity was performed to determine the roles of hub genes. Results: There were 562 dysregulated genes, while 12 genes were hub genes. NUF2 was established to be a candidate immunotherapeutic target with potential clinical implications. The 12 hub genes were highly enriched in the p53 signaling pathway, the cell cycle, progesterone-associated oocyte maturation, cellular senescence, and oocyte meiosis. Survival analysis showed that NUF2 is associated with NSCLC occurrence, invasion, and recurrence. Conclusion: The NUF2 gene discovered in this study helps us clarify the pathomechanisms of NSCLC occurrence as well as progression and provides a potential diagnostic and therapeutic target for NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Proteínas de Ciclo Celular , Neoplasias Pulmonares , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Proteínas de Ciclo Celular/genética , Biologia Computacional , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Prognóstico , Proteína Supressora de Tumor p53/genética
7.
Oncotarget ; 8(55): 94481-94492, 2017 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-29212243

RESUMO

Rab27a, a member of the Rab protein family, can regulate the tumor microenvironment and promote the development of the tumor. Elevated expression of Rab27a is closely connected with many human cancers containing non-small cell lung cancer (NSCLC). But the role of Rab27a in non-small cell lung cancer and its possible mechanism is particularly unclear. In this research, we explored the effect of silencing Rab27a in vitro and in vivo, furnishing evidence that Rab27a could be a potential therapeutic target in NSCLC. Compared with corresponding control cells, silencing Rab27a had decreased ability of cell proliferation, migration and invasion in vitro and slower growth of xenograft tumors in mice. The expressions of apoptosis-associated proteins were induced with a reduction of anti-apoptotic protein in the NSCLC cells down-regulated Rab27a. Furthermore, Rab27a was associated with resistance to conventional chemotherapeutic agents. Our findings suggested that Rab27a might play a critical role in increasing chemosensitivity in NSCLC.

8.
Acta Biochim Biophys Sin (Shanghai) ; 49(8): 680-688, 2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-28575188

RESUMO

OTUB1 (OTU domain-containing ubiquitin aldehyde binding protein 1) is a deubiquitinating enzyme (DUB) that belongs to the ovarian tumor (OTU) domain protease superfamily. Although it has been demonstrated to play important roles in the development of many kinds of cancer, the mechanism of OTUB1 in hepatocellular carcinoma (HCC) is not clear. The aim of this study was to explore the roles of OTUB1 in HCC progression using cell lines and 115 archived HCC samples. In addition, the clinical outcomes were also analyzed with a special focus on OTUB1 expression in HCC samples. In the immunohistochemical study, OTUB1 showed high expression in 60 of the 115 cases (52.2%). The OTUB1 expression level was significantly correlated with many clinicopathological parameters, including TNM stage (P = 0.002), histology stage (P = 0.002), and metastasis/recurrence (P = 0.016). Survival analysis showed that the group with OTUB1 overexpression had significantly shorter overall survival time than the group with OTUB1 downregulation (hazard ratio [HR] = 0.482; confidence interval [CI]: 0.311-0.748; P = 0.001). Multivariate analysis indicated that OTUB1 expression was a significant and independent prognostic parameter (HR = 0.214; CI: 0.126-0.364; P < 0.001) for HCC patients. The ability of HCC cells to undergo proliferation, migration, and invasion was suppressed by disruption of endogenous OTUB1 using short hairpin RNA (shRNA). OTUB1 expression appears to be a new and independent predictor for the prognosis of HCC patients. Overexpression of OTUB1 in HCC could be a novel, effective, and supplementary biomarker for HCC because it plays a vital role in the progression of HCC.


Assuntos
Carcinoma Hepatocelular/metabolismo , Movimento Celular , Cisteína Endopeptidases/biossíntese , Neoplasias Hepáticas/metabolismo , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/cirurgia , Linhagem Celular Tumoral , Cisteína Endopeptidases/genética , Enzimas Desubiquitinantes , Progressão da Doença , Feminino , Células Hep G2 , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Interferência de RNA
9.
J Laparoendosc Adv Surg Tech A ; 27(7): 676-684, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28326886

RESUMO

PURPOSE: To investigate the risk factors for recurrence and treatment strategies after patients with hepatocellular carcinoma (HCC) undergo total laparoscopic hepatectomy (LH). METHODS: The study included 109 patients who underwent LH (laparoscopy resection [LR] group, n = 50) or open hepatectomy [OH] (open resection [OR] group, n = 59) for HCC in our hospital between March 2011 and June 2016. Perioperative outcomes, disease recurrence, survival, and risk factors for recurrence were analyzed. RESULTS: Patient characteristics did not significantly differ between groups. The 1- and 3-year survival rates were 90.7% and 78.1%, respectively, for the LR group and 83.1% and 74.4%, respectively, for the OR group (P = .71). The 1- and 3-year disease-free survival rates were 89.6% and 51.4%, respectively, for the LR group and 84.7% and 59.6%, respectively, for the OR group (P = .935). Tumor size, differentiation, vascular invasion, surgical bleeding, and surgical resection margin were risk factors for tumor recurrence after LH. CONCLUSION: LH for HCC did not increase the risk of recurrence compared with OH. Tumor size, differentiation, vascular invasion, surgical bleeding, and surgical resection margin were risk factors for tumor recurrence. Reducing bleeding during surgery and ensuring sufficient surgical margins were the most important measures to reduce postoperative recurrence of HCC.


Assuntos
Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/mortalidade , Recidiva Local de Neoplasia/mortalidade , Perda Sanguínea Cirúrgica , Carcinoma Hepatocelular/cirurgia , China/epidemiologia , Intervalo Livre de Doença , Feminino , Hepatectomia , Humanos , Laparoscopia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Complicações Pós-Operatórias , Fatores de Risco
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