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J Transl Med ; 18(1): 40, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32000807


BACKGROUND: Hepatocellular carcinoma (HCC) is the most common type of liver tumour, and is closely related to liver cirrhosis. Previous studies have focussed on the pathogenesis of liver cirrhosis developing into HCC, but the molecular mechanism remains unclear. The aims of the present study were to identify key genes related to the transformation of cirrhosis into HCC, and explore the associated molecular mechanisms. METHODS: GSE89377, GSE17548, GSE63898 and GSE54236 mRNA microarray datasets from Gene Expression Omnibus (GEO) were analysed to obtain differentially expressed genes (DEGs) between HCC and liver cirrhosis tissues, and network analysis of protein-protein interactions (PPIs) was carried out. String and Cytoscape were used to analyse modules and identify hub genes, Kaplan-Meier Plotter and Oncomine databases were used to explore relationships between hub genes and disease occurrence, development and prognosis of HCC, and the molecular mechanism of the main hub gene was probed using Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis. RESULTS: In total, 58 DEGs were obtained, of which 12 and 46 were up- and down-regulated, respectively. Three hub genes (CDKN3, CYP2C9 and LCAT) were identified and associated prognostic information was obtained. CDKN3 may be correlated with the occurrence, invasion, and recurrence of HCC. Genes closely related to changes in the CDKN3 hub gene were screened, and Kyoto Encyclopedia of Genes and Genomes (KEGGs) pathway analysis identified numerous cell cycle-related genes. CONCLUSION: CDKN3 may affect the transformation of liver cirrhosis into HCC, and represents a new candidate molecular marker of the occurrence and progression of HCC.

Future Oncol ; 14(20): 2005-2011, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29513033


AIM: To explore the association between the determinant factors including HLA-DQB1*03, DRB1-*07, -*13 and high-risk HPV infection, the cervical squamous cell carcinoma (CSCC) pathogenesis among Chinese Uighur and Han population. MATERIALS & METHODS: HLA alleles were genotyped by PCR sequence-specific primers. RESULTS: HPV16 infection rate was significantly higher among the Uighurs and Hans with CSCC as compared with healthy controls, respectively. HLA-DQB1*03 significantly increased among Uighurs with CSCC, while HLA-DRB1*07 significantly increased among Hans with CSCC. Similar tendencies were observed for DQB1*03 with HPV16-positive Uighurs CSCC and DRB1*07 with HPV16-positive Hans CSCC. CONCLUSION: This study suggests that HLA-DQB1*03 and DRB1*07 alleles may influence the immune response to HPV16 infection and increase the risk of CSCC among the Uighurs and Hans in China.

Alelos , Grupos Étnicos/genética , Predisposição Genética para Doença , Cadeias beta de HLA-DQ/genética , Neoplasias do Colo do Útero/genética , Adulto , Idoso , China/epidemiologia , Feminino , Papillomavirus Humano 16 , Humanos , Pessoa de Meia-Idade , Razão de Chances , Infecções por Papillomavirus/virologia , Medição de Risco , Análise de Sequência de DNA , Neoplasias do Colo do Útero/virologia , Adulto Jovem
Oncotarget ; 8(13): 21526-21538, 2017 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-28423526


M2 macrophages was domesticated by tumor microenvironment to produce some angiogenic molecules and protease, facilitating angiogenesis and matrix breakdown, promoting tumor invasive and metastasis. However, The function of M2 macrophages to progression of eophageal carcinoma, especially Kazakh esophageal carcinoma is still dimness. This study aims to investigate M2 macrophages correlated with matrix metalloproteinase-9 (MMP9) and microvessel density, and the role in the progression of Kazakh esophageal squamous cell carcinoma. CD163 and CD34 as the marker of M2 macrophages and endothelial cells, were used to identify the M2 macrophages density and microvessel density, respectively. Immunohistochemistry staining was evaluated the expression of MMP9. The number of infiltrated CD163-positive M2 macrophages in tumor islets and stroma was significantly higher than in cancer adjacent normal tissues. The increased of M2 macrophages and microvessel density were significantly correlated with more malignant phenotypes including lymph node metastasis and clinical stage progression. Meanwhile, the expression of MMP9 showed much higher level in esophageal squamous cell carcinoma than that in cancer adjacent normal tissues, and high expression of MMP9 in Kazakh esophageal squamous cell carcinoma was significantly associated with age, depth of tumor invasion, lymph node metastasis, and tumor clinical stage. The quantity of M2 macrophages in tumor stroma was positively associated with microvessel density and the expression of MMP9, and as an independent poorly prognostic factor for overall survival time of Kazakh esophageal squamous cell carcinoma. These findings suggest the increased number of M2 macrophages correlated with high expression of MMP9 and high microvessel density may contribute to the tumor aggressiveness and angiogenesis, promoting the progression of Kazakh esophageal squamous cell carcinoma.

Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/patologia , Macrófagos/imunologia , Neovascularização Patológica/patologia , Microambiente Tumoral/imunologia , Adulto , Idoso , Antígenos CD/imunologia , Antígenos de Diferenciação Mielomonocítica/imunologia , Grupo com Ancestrais do Continente Asiático , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/mortalidade , Neoplasias Esofágicas/imunologia , Neoplasias Esofágicas/mortalidade , Carcinoma de Células Escamosas do Esôfago , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Ativação de Macrófagos/imunologia , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Receptores de Superfície Celular/imunologia
APMIS ; 121(10): 908-18, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23659763


Three recent large-scale genome-wide association studies (GWAS) in Chinese Han populations have identified an esophageal squamous cell carcinoma (ESCC) susceptibility locus within phospholipase C epsilon 1 (PLCE1) gene, which encodes a phospholipase involved in intracellular signaling. The expressed PLCE1 in ESCC, however, are inconsistent. This study examined PLCE1 expression by immunohistochemistry (IHC) from 110 ethnic Kazakh ESCC patients and 50 from adjacent normal esophageal tissues (NETs). The expressed PLCE1 was localized in cytoplasm, especially in the peripheral layers of cancer cell nests, which was significantly higher in tumors than in NETs (p < 0.001). Increased expression of PLCE1 was correlated with advanced tumor-node-metastasis (TNM) stages (p = 0.015) and lymph node metastasis (p = 0.003) in patients with ESCC. Of the 110 patients, we examined 50 paired ESCC tissues and corresponding NETs by quantitative RT-PCR (polymerase chain reaction) and the mean mRNA level of PLCE1 in ESCC was 1.85-fold higher compared with those in corresponding NETs (p = 0.0012). Meanwhile, 4 of 5 ESCC cell lines also showed elevated expression of PLCE1 mRNA. Furthermore, elevated expression of PLCE1 mRNA in Kazakh ESCC was associated with its immunoreactivity (ρ = 0.297, p = 0.040), lymph node metastasis (p < 0.001), and advanced TNM stages of ESCC (p = 0.013). To our knowledge, this study demonstrates for the first time that PLCE1 overexpression correlates with lymph node metastasis and advanced TNM stages of Kazakh ESCC, implicating a role of PLCE1 in cancer metastasis and aggressiveness in ethnic Kazakh patients with ESCC. Furthermore, the current findings may warrant investigations into whether inhibiting PLCE1 could be a strategy for targeted anticancer therapy particularly for Kazakh ESCC.

Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Fosfoinositídeo Fosfolipase C/genética , Carcinoma de Células Escamosas/etnologia , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , China/epidemiologia , Neoplasias Esofágicas/etnologia , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago , Esôfago , Feminino , Expressão Gênica , Estudo de Associação Genômica Ampla , Humanos , Cazaquistão/etnologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 24(3): 341-4, 2007 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-17557253


OBJECTIVE: To analyze the mutations of BRCA1 in breast cancer patients of Uigur women in Xinjiang. METHODS: By using single strand conformation polymorphism (SSCP) and DNA sequencing, BRCA1 mutations were detected in 70 Uigur women breast cancer cases and 32 cases of benign breast diseases and non-tumor tissue next to carcinoma. RESULTS: (1) 12 new loci of BRCA1 gene mutation were detected firstly in 70 Uigur women breast cancer patients. (2)The frequency of BRCA1 mutation in 70 Uigur women breast cancer cases was 12.86% (9/70). The frequency of BRCA1 mutation in Uigur women early onset breast cancer was 31.82% (7/22), which was significantly higher than that in late onset group (2/48, 4.16%) (chi(2) =10.295, P<0.01). (3) There were BRCA1 gene polymorphisms in 9 of 70 Uigur women breast cancer patients. The loci of polymorphisms in 8 of 9 cases were 3232A>G. (4)In the research group two cases of bilateral breast cancer were found with BRCA1 gene mutation. CONCLUSION: The mutation of BRCA1 gene may be related to Uigur women breast cancer and bilateral breast cancer.

Grupo com Ancestrais do Continente Asiático/genética , Neoplasias da Mama/genética , Grupos Étnicos/genética , Genes BRCA1 , Mutação , Adulto , Idoso , China , Feminino , Humanos , Íntrons/genética , Pessoa de Meia-Idade , Polimorfismo Conformacional de Fita Simples