RESUMO
BACKGROUND: Genetic polymorphisms of Toll-like receptors play important roles in gastric carcinogenesis. The aim of this study was to determine the role of TLR2-196 to -174 ins/del polymorphism in gastric cancer susceptibility and prognosis. METHODS: This study included 520 people from southern China. Samples were genotyped by the allele-specific polymerase chain reaction, among which 10% were randomly selected for sequencing. The serological method was used to determine Helicobacter pylori. RESULTS: The TLR2 genotype was not associated with the risk of H. pylori infection. The del/del genotype exhibited significantly higher gastric cancer risk (adjusted OR 2.59, 95% CI 1.33â5.07) than that of the ins/ins genotype. Further stratification analyses demonstrated that the del/del genotype was associated with a risk of intestinal gastric cancer (adjusted OR 2.62, 95% CI 1.34-5.14). In addition, the presence of the del/del genotype and the H. pylori infection conferred a synergistic effect (OR 3.04, 95% CI 1.33â6.98) for the development of gastric cancer. The del/del genotype was not associated with a poor prognosis in gastric cancer patients. CONCLUSION: The del/del genotype is associated with an increased gastric cancer risk in the southern Chinese population. However, TLR2 polymorphism is neither associated with H. pylori infection, nor with a poor prognosis.
Assuntos
Adenocarcinoma/genética , Infecções por Helicobacter/genética , Polimorfismo Genético , Neoplasias Gástricas/genética , Receptor 2 Toll-Like/genética , Adenocarcinoma/microbiologia , Adenocarcinoma/mortalidade , Idoso , Povo Asiático/genética , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Infecções por Helicobacter/complicações , Helicobacter pylori/patogenicidade , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Prognóstico , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/mortalidadeRESUMO
Macrophages play a critical role in the initiation and progression of various solid tumors. However, their prognostic significance in pancreatic ductal adenocarcinoma (PDAC) is poorly understood. This study investigated the distribution patterns of macrophages in PDAC and possible association with the overall survival (OS). We found significant differences in macrophage density (identified by CD68 and CD163 immunopositivity; p < 0.001 for both) between primary cancer and paired adjacent normal tissues. Most macrophages in cancerous pancreatic tissues were located in the stroma rather than the islets (p = 0.032 and p < 0.001). We also demonstrated that a high total macrophage density (characterized by CD68 immunopositivity) correlated with an absence of jaundice before surgery (p = 0.03) and that a high density of M2 macrophages (characterized by CD163 immunopositivity) in the stroma strongly correlated with the tumors located in the tail and body of the pancreas (p = 0.04). In addition, OS was shorter in patients with high-density M2 macrophage infiltration than in those with low-density M2 macrophage infiltration (p = 0.012). Moreover, multivariate analysis revealed that dense M2 macrophage infiltration into the stroma was an independent prognostic factor for PDAC patients (p = 0.02).
Assuntos
Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Biomarcadores Tumorais/análise , Carcinoma Ductal Pancreático/patologia , Macrófagos/patologia , Neoplasias Pancreáticas/patologia , Receptores de Superfície Celular/metabolismo , Células Estromais/patologia , Carcinoma Ductal Pancreático/metabolismo , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Macrófagos/metabolismo , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Pancreáticas/metabolismo , Fenótipo , Prognóstico , Células Estromais/metabolismo , Taxa de Sobrevida , Análise Serial de Tecidos , Células Tumorais CultivadasRESUMO
OBJECTIVE: To determine a risk scoring system for predicting advanced colorectal neoplasia (ACN) within subcentimetric polyps in a large Asian population. METHODS: A retrospective study was conducted in Hong Kong SAR, China involving participants who underwent colonoscopy between 2008 and 2015. A random sample of 20 072 subjects were included as the derivation cohort to assess ACN-associated independent factors using logistic regression modeling. Another 8603 subjects formed a validation cohort. A risk scoring system was developed and its performance was assessed using the area under the receiver operating characteristic curve (AUROC). RESULTS: The risk scores were assigned based on the following criteria: (a) patients who were admitted from inpatient colonoscopy (2.2) or not (1); (b) with three or more chronic diseases (hypertension, diabetes mellitus, hyperlipidemia, heart disease, or cancer) (1.7) or not (1); (c) anemia (1.3) or without anemia (1); (d) receiving aspirin (0.5) or not (1); (e) receiving other nonsteroidal anti-inflammatory drugs (0.3) or not (1); (f) male (1.2) or female gender (1); (g) age <55 (1), 55-64 (1.4), 65-69 (2), 70 years or above (2.2). ACN was more common in those with scores of 2.192 or higher, and they were classified as high risk (HR). The prevalence of ACN in the validation cohort was 13.28% and 3.56% in the HR and low-risk groups, respectively. In both the derivation and validation cohorts, AUROC of the risk-scoring model was 0.7138. CONCLUSION: Physicians are recommended to utilize this validated score for risk-stratification of patients having subcentimetric polyps.
RESUMO
Emerging evidence revealed the critical role of systematic inflammation in pancreatic ductal adenocarcinoma (PDAC). In the present study, we reviewed the records of 279 patients with advanced PDAC. Among them, 147 cases were used as the training cohort and another 132 as the validation cohort. In the training cohort, distant metastasis, carbohydrate antigen 19-9 (CA19-9), Glasgow prognostic score (GPS), neutrophil-to-lymphocyte ratio (NLR), and lymphocyte-to-monocyte ratio (LMR) were independent prognostic factors in Cox regression. A nomogram based on these factors was generated to predict median survival time and survival probabilities at 6, 12, and 18 months. The nomogram showed a better discriminatory ability than the American Joint Committee on Cancer (AJCC) TNM staging (C-index: 0.727 vs. 0.610). In the validation cohort, a nomogram composed of the same variables also showed a high discriminatory ability (C-index: 0.784). In the low-risk group with a nomogram total point (NTP) value of more than 175, patients receiving combination therapy showed better prognosis than those receiving monotherapy (P=0.015). In conclusion, the nomogram based on inflammatory biomarkers can serve as useful prognostic tool for advanced PDAC. In addition, patients with high NTP can greater benefit from combination chemotherapy than monotherapy.
RESUMO
Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with few therapeutic options. Recently, insight into cancer biology suggested abnormal lipid metabolism to be a risk factor for human malignancies. As a key enzyme implicated in lipid metabolism, PLD1 was elevated in various human cancer associating with malignant phenotypes. However, little was known about its expression and function in PDAC. We showed that PLD1 was elevated in both the cell lines and clinical samples of PDAC, and it positively correlated with vascular invasion (p = 0.041) and responsible for a poor prognosis (p = 0.009). Meanwhile, we also found Sp1 to be elevated in the disease, correlating with vascular invasion (p = 0.007). Moreover, the correlation assay suggested that PLD1 positively correlated with Sp1 in the clinical sample (r = 0.390; p < 0.001) and the cell lines. Finally, we showed that co-high expression of both the factors confers the poorest prognosis for the patients, and that their simultaneous high expression might be an independent prognostic factor (p = 0.001; HR = 3.427; 95% CI 1.629-7.211).