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1.
Zhonghua Wei Chang Wai Ke Za Zhi ; 23(1): 65-70, 2020 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-31958933

RESUMO

Objective: To study the relationship of liver function index alanine aminotransferase and aspartate aminotransferase ratio (LSR) with clinicopathological factors in patients with gastric cancer and its clinical significance in predicting the survival of patients. Methods: A retrospective case-control study was used. Retrospective analysis was conducted on 891 patients with advanced gastric cancer who underwent gastric cancer surgery at the Gastrointestinal Surgery Department of Harbin Medical University Cancer Hospital from January 2007 to December 2010, having complete postoperative clinicopathological and follow-up data. Case inclusion criteria: (1) preoperative definite diagnosis of gastric cancer, residual gastric cancer and other gastric tumors were excluded; (2) no neoadjuvant therapy before surgery; (3) no other serious diseases such as acute coronary heart disease, cirrhosis, chronic renal failure, etc.; (4) radical gastrectomy was performed, palliative treatment or open laparotomy cases were excluded; (5) complete postoperative pathological data, complete follow-up information; (6) cause of death was associated with gastric cancer. Blood examination was performed during hospitalization. The best cut-off points of LSR, hemoglobin, lymph node metastasis rate, maximum diameter of tumors, alkaline phosphatase, glutamyl transpeptidase, total bilirubin and lactate dehydrogenase were obtained by using receiver operating characteristic curve(ROC). Patients were divided into two groups according to best LSR cut-off points. The relationship between LSR and clinicopathological factors was analyzed, and the overall survival rate of different LSR groups was compared. Relevant clinical factors and LSR were included in the univariate and multivariate survival analysis using the Cox method. Results: The best cut-off point of LSR in ROC curve was 1.43, and 682 cases in LSR<1.43 group, 209 cases in LSR≥1.43 group. The best cut-off points of hemoglobin, lymph node metastasis rate, maximum diameter of tumors, alkaline phosphatase, glutamyl transpeptidase, total bilirubin and lactate dehydrogenase were 130.2 g/L, 18.0%, 4.75 cm, 68.1 U/L, 16.55 U/L, 5.58 µmol/L and 135.8 U/L, respectively. Between patients with LSR<1.43 and LSR≥1.43, age (χ(2)=4.412, P=0.036), depth of tumor invasion (χ(2)=64.306, P<0.001), histological type (χ(2)=8.026, P=0.005), alkaline phosphatase (χ(2)=8.217, P=0.004), glutamyl transpeptidase (χ(2)=33.207, P<0.001), total bilirubin (χ(2)=14.012, P<0.001) and lactate dehydrogenase (χ(2)=63.630, P<0.001) were significantly different. The 1-, 3- and 5-year survival rates of LSR<1.43 group and LSR≥1.43 group were 70.8%, 31.3%, 25.0% and 64.9%, 24.4%, 11.3% respectively, whose difference was significant (χ(2)=10.140, P=0.001). Univariate analysis showed that age, hemoglobin, TNM stage, depth of invasion, lymph node metastasis rate, lymph node metastasis, histological type, maximum diameter of tumors, glutamyl transferase, total bilirubin and LSR were associated with overall survival of gastric cancer (all P<0.05). Multivariate analysis showed that tumor TNM stage (HR=1.605, 95%CI: 1.332 to 1.936, P<0.001), tumor invasion depth (HR=1.299, 95%CI: 1.168 to 1.445, P<0.001), lymph node metastasis rate (HR=2.400, 95%CI:1.873 to 3.076, P<0.001), lymph node metastasis (HR=1.263, 95%CI: 1.106 to 1.478, P=0.007), maximum tumor diameter (HR=1.375, 95%CI: 1.134 to 1.669, P=0.001), and LSR (HR=1.427, 95%CI: 1.190 to 1.711, P<0.001) were independent risk factors for the prognosis of patients with gastric cancer. Conclusions: LSR is an independent risk factor for the prognosis of gastric cancer patients, and the detection is simple and easy. It is a potential marker for the prognosis of gastric cancer. Therefore, in the preoperative comprehensive management stage, it should be possible to restore and improve the liver function in order to obtain a better prognosis of gastric cancer and prolong the survival time of patients.


Assuntos
Alanina Transaminase/sangue , Neoplasias Gástricas/sangue , Neoplasias Gástricas/cirurgia , Transaminases/sangue , Gastrectomia/mortalidade , Humanos , Hepatopatias/sangue , Hepatopatias/mortalidade , Testes de Função Hepática , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Período Pré-Operatório , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Neoplasias Gástricas/mortalidade , Análise de Sobrevida
2.
Anticancer Res ; 40(1): 239-244, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892572

RESUMO

BACKGROUND: In previous studies, we demonstrated the significant role of microRNA-449a (miR-449a) in colorectal cancer with in vivo and clinical samples. The importance of miR-449a in gastric cancer is still to be elucidated. This study examined the impact of miR-449a expression in tumor tissue and serum and investigated its potential as a prognostic marker in gastric cancer. MATERIALS AND METHODS: Sixty-six patients with gastric cancer who underwent surgery were included in the study. miR-449a expression in tumor tissue and serum were investigated by real-time polymerase chain reaction analysis. The association of miR-449a expression with clinicopathological factors and patient prognosis were also investigated. RESULTS: miR-449a expression was lower in tumor tissue than non-tumor tissue. miR-449a in tumor tissue negatively correlated with the malignancy of tumor and clinical stage. Increased carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels were seen at significantly higher frequencies in patients with low miR-449a expression. Patients with low miR-449a expression had poorer cancer-specific survival compared to those with high miR-449a expression. The univariate analysis showed that lymphovascular invasion, increased CEA and CA19-9 and a low expression of miR-449a were associated with a poorer 5-year cancer-specific survival. miR-449a expression level in serum correlated to that in tumor tissue and was also associated with tumor malignancy. CONCLUSION: The miR-449a level in tumor tissue might be useful as a prognostic indicator for patients with gastric cancer and miR-449a in serum appears to reflect its expression in tumor tissue.


Assuntos
Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Neoplasias Gástricas/genética , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Masculino , MicroRNAs/sangue , MicroRNAs/metabolismo , Prognóstico , Neoplasias Gástricas/sangue
3.
Anticancer Res ; 39(11): 6125-6133, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704840

RESUMO

AIM: The aim of the study was to identify novel biomarkers that are vital for improving management of patients with gastric cancer (GC). MATERIALS AND METHODS: An RNA-sequencing analysis was conducted using gastric tissue from patients with metastatic GC. In vitro cell functions were evaluated by siRNA-mediated knockdown assays. A total of 230 pairs of gastric tissue were subjected to expression analysis of mRNA and protein in situ. The serum levels of the candidate biomarker were determined by ELISA. RESULTS: MELTF was identified as a candidate biomarker. Inhibition of MELTF expression suppressed the invasion ability of GC cells. Increased tissue MELTF mRNA expression was associated with shorter survival. Furthermore, staining intensity of tissue MELTF protein was linked to recurrence rates. Serum MELTF levels gradually were increased from healthy controls to advanced GC. Patients with high serum MELTF levels had poor prognosis. CONCLUSION: Both tissue and serum MELTF levels may serve as biomarkers of GC progression.


Assuntos
Adenocarcinoma/patologia , Biomarcadores Tumorais/metabolismo , Glicoproteínas de Membrana/metabolismo , Recidiva Local de Neoplasia/patologia , Neoplasias Gástricas/patologia , Adenocarcinoma/sangue , Adenocarcinoma/metabolismo , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , Proliferação de Células , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Glicoproteínas de Membrana/sangue , Glicoproteínas de Membrana/genética , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Neoplasias Gástricas/sangue , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/cirurgia , Células Tumorais Cultivadas
4.
Medicine (Baltimore) ; 98(46): e17954, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31725654

RESUMO

BACKGROUND: Published studies have investigated the prognostic roles of estrogen receptor alpha (ERα) and estrogen receptor beta (ERß) in gastroesophageal cancer patients with the controversial results. The aim of the study was to systematically evaluate the impacts of ERα and ERß on the overall survival (OS) in patients. METHOD: Relevant eligible studies were extracted from PubMed, Embase, Web of Science, CNKI and Wanfang databases (from the start date to November 2018) following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. HR (hazard ratio) with 95% confidence intervals (CIs) were used to assess the prognostic values of ERα and ERß for OS in patients. RESULTS: High ERα expression was associated with poor OS (HR = 1.58, 95% CI = 1.29-1.94, P < .001) and ERß with better OS (HR = 0.56, 95% CI = 0.37-0.83, P = .004) in gastroesophageal cancer. Furthermore, unfavorable OS was found in Chinese gastroesophageal patients with higher ERα expression (HR = 1.57, 95% CI = 1.25-1.96, P < .001) and better OS with higher ERß expression (HR = 0.51, 95% CI = 0.31-0.83, P < .01) in our subgroup analysis. Meanwhile, worse OS was found in esophageal squamous cell carcinoma (ESCC) patients with high ERα expression (HR = 1.74, 95% CI = 1.33-2.26, P < .001), and favorable OS in ESCC with ERß overexpression (HR = 0.40, 95% CI = 0.31-0.52, P < .001). Besides, high ERα expression was associated with lower tumor differentiation in ESCC (OR = 1.64; 95% CI = 1.02-2.64, P = .04) and ERß was linked with better tumor differentiation in gastric adenocarcinoma (GCA) (OR = 0.49; 95% CI = 0.26-0.94, P = .03). CONCLUSIONS: ERα and ERß might serve as potential prognostic biomarkers for gastroesophageal cancer patients. ERα overexpression predicted poor OS and lower tumor differentiation, and ERß suggested favorable OS and better tumor differentiation. Further related studies should be performed to test these results.


Assuntos
Neoplasias Esofágicas/mortalidade , Receptor alfa de Estrogênio/biossíntese , Receptor beta de Estrogênio/biossíntese , Neoplasias Gástricas/mortalidade , Biomarcadores Tumorais , China/epidemiologia , Neoplasias Esofágicas/sangue , Neoplasias Esofágicas/patologia , Receptor alfa de Estrogênio/sangue , Receptor beta de Estrogênio/sangue , Humanos , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias Gástricas/sangue , Neoplasias Gástricas/patologia , Análise de Sobrevida
5.
Medicine (Baltimore) ; 98(43): e17432, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31651846

RESUMO

BACKGROUND: Several studies have explored the prognostic value of stanniocalcin 2 (STC2) in various cancers, but obtained inconsistent results. Therefore, this meta-analysis was performed to determine the prognostic and clinicopathologic significance of STC2 in various cancers. METHODS: Eligible studies were identified by searching the online databases PubMed, Embase, Web of Science, and the China National Knowledge Infrastructure up to March 2019. Hazard ratios (HRs) with 95% confidence intervals (CIs) and were calculated to clarify the correlation between STC2 expression and prognosis of different cancers. Odds ratios (ORs) with 95% CI were selected to appraise the correlation between STC2 with clinicopathologic characteristics of patients with cancer. RESULTS: A total of 16 eligible studies with 4074 patients with cancer were included in our meta-analysis. The results showed that high STC2 expression can predict poor overall survival (OS) for cancer (HR = 1.48, 95% CI: 1.15-1.90, P = .002). Subgroup analysis found that high STC2 expression was associated with worse OS in Asian (HR = 1.85, 95% CI: 1.35-2.55), the reported directly from articles group (HR = 1.39, 95% CI: 1.05-1.84), survival curves group (HR = 1.93, 95% CI: 1.36-2.74), and gastric cancer (HR = 1.43, 95% CI: 1.04-1.95). Furthermore, high STC2 expression was significantly related to advanced T stage (OR = 1.83, 95% CI: 1.17-2.86, P = .008), lymph node metastasis (OR = 2.29, 95% CI: 1.51-3.45, P < .001), lymphatic invasion (OR = 2.15, 95% CI: 1.53-3.02, P < .001), venous invasion (OR = 1.97, 95% CI: 1.30-2.99, P = .001), and more advanced clinical stage (OR = 2.36, 95% CI: 1.74-3.19, P < .001) CONCLUSION:: Elevated expression of STC2 suggested a poor prognosis in patients with cancer and may serve as a new tumor marker to monitor cancer development and progression.


Assuntos
Glicoproteínas/sangue , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Neoplasias/sangue , Neoplasias/mortalidade , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Biomarcadores Tumorais/sangue , Feminino , Humanos , Metástase Linfática/genética , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Estadiamento de Neoplasias , Neoplasias/patologia , Razão de Chances , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias Gástricas/sangue , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia
6.
Anticancer Res ; 39(9): 5195-5201, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519633

RESUMO

BACKGROUND/AIM: Cancer immune therapy by immune checkpoint inhibitors (ICIs) is a promising therapeutic strategy for various cancer types. Among ICIs, anti-programmed cell death protein-1 (PD1) and anti-programmed death-ligand 1 (PD-L1) antibodies have shown a remarkable clinical benefit. The present study aimed to address the functional and clinical significance of serum levels of soluble PD-L1 (sPD-L1) in patients. MATERIALS AND METHODS: A total of 21 patients, 11 with NSCLC, nine with gastric cancer and one with bladder cancer, who underwent anti-PD-1 therapy were evaluated for sPD-L1 concentration by ELISA analyses at diagnosis and after treatment. RESULTS: Pretreatment levels of sPD-L1 in patients who received ICIs were not remarkably correlated with the overall survival of these patients (r=0.3394, p=0.1323). Reduction of plasma sPD-L1 level was significantly correlated with tumor regression in patients administered four cycles of treatment (p<0.05). CONCLUSION: sPD-L1 might be derived and secreted from tumors and might be useful to identify primary responders to ICIs at a relatively early treatment timepoint.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Antígeno B7-H1/sangue , Biomarcadores Tumorais , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/patologia , Neoplasias Gástricas/sangue , Neoplasias Gástricas/patologia , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/farmacologia , Antígeno B7-H1/antagonistas & inibidores , Progressão da Doença , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico , Resultado do Tratamento
7.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 48(3): 326-333, 2019 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-31496166

RESUMO

Early diagnosis is the key to improve the prognosis of gastric cancer. How to screen out high-risk subjects of gastric cancer in population is a hot spot. Serum-based early detection of gastric cancer is suitable for high-risk population screening, which is more convenient and safer. This article reviews the diagnostic value of serum biomarkers for gastric cancer, including serum DNA methylation, various RNAs, pepsinogen, gastrin, osteopontin, MG7-Ag and CA724. Until now, there is still lack of ideal biomarkers for gastric cancer, and searching for specific RNAs may be promising for early diagnosis and screening of gastric cancer.


Assuntos
Biomarcadores Tumorais , Detecção Precoce de Câncer , Neoplasias Gástricas , Biomarcadores Tumorais/sangue , Detecção Precoce de Câncer/tendências , Humanos , Sensibilidade e Especificidade , Neoplasias Gástricas/sangue , Neoplasias Gástricas/diagnóstico
8.
Nat Med ; 25(9): 1428-1441, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31501614

RESUMO

Psychological distress has long been suspected to influence cancer incidence and mortality. It remains largely unknown whether and how stress affects the efficacy of anticancer therapies. We observed that social defeat caused anxiety-like behaviors in mice and dampened therapeutic responses against carcinogen-induced neoplasias and transplantable tumors. Stress elevated plasma corticosterone and upregulated the expression of glucocorticoid-inducible factor Tsc22d3, which blocked type I interferon (IFN) responses in dendritic cell (DC) and IFN-γ+ T cell activation. Similarly, close correlations were discovered among plasma cortisol levels, TSC22D3 expression in circulating leukocytes and negative mood in patients with cancer. In murine models, exogenous glucocorticoid injection, or enforced expression of Tsc22d3 in DC was sufficient to abolish therapeutic control of tumors. Administration of a glucocorticoid receptor antagonist or DC-specific Tsc22d3 deletion reversed the negative impact of stress or glucocorticoid supplementation on therapeutic outcomes. Altogether, these results indicate that stress-induced glucocorticoid surge and Tsc22d3 upregulation can subvert therapy-induced anticancer immunosurveillance.


Assuntos
Imunidade Celular , Neoplasias/imunologia , Estresse Psicológico/imunologia , Fatores de Transcrição/genética , Animais , Ansiedade/sangue , Ansiedade/induzido quimicamente , Ansiedade/imunologia , Ansiedade/psicologia , Comportamento Animal/fisiologia , Carcinógenos/toxicidade , Neoplasias Colorretais/sangue , Neoplasias Colorretais/genética , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/psicologia , Corticosterona/sangue , Células Dendríticas/transplante , Regulação Neoplásica da Expressão Gênica , Glucocorticoides/farmacologia , Humanos , Hidrocortisona/sangue , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/psicologia , Ativação Linfocitária/genética , Camundongos , Monitorização Imunológica/métodos , Neoplasias/induzido quimicamente , Neoplasias/genética , Neoplasias/psicologia , Receptores de Glucocorticoides/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Neoplasias Gástricas/sangue , Neoplasias Gástricas/genética , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/psicologia , Estresse Psicológico/induzido quimicamente , Estresse Psicológico/genética , Estresse Psicológico/terapia , Fatores de Transcrição/imunologia
9.
Clin Lab ; 65(12)2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31414587

RESUMO

BACKGROUND: Screening and timely treatment of precancerous gastric cancer diseases or of gastric cancer in the early stages has important significance in reducing the incidence and mortality of gastric cancer. Gastroscopy and histopathological biopsy are still the gold standards for the diagnosis of gastric diseases. But the application of astroscopy for the screening and diagnosis of gastric diseases is limited. In recent years, serum pepsinogen (PG), gastrin, and Helicobacter pylori (H. pylori) IgG antibodies have become indicators for "serological biopsy" of the gastric mucosa. METHODS: From January 2016 to January 2018, a total of 2,394 patients with digestive tract symptoms underwent gastroscopy. According to the endoscopic examination and pathological diagnosis, there were four case groups: 1,376 cases of chronic non-atrophic gastritis, 708 cases of chronic atrophic gastritis, 265 cases of gastric ulcer, and 45 cases of gastric cancer. Serological gastric biopsies were performed and analyzed. RESULTS: The serum levels of PGI in the chronic atrophic gastritis group was significantly lower than that in the chronic non-atrophic gastritis group, gastric ulcer group, and gastric cancer group (p < 0.05). The serum levels of PGII and G-17 in the gastric cancer group were significantly higher than those in the chronic non-atrophic Gastritis group, chronic atrophic gastritis group, and gastric ulcer group (p < 0.05). The PGR in the gastric cancer group was significantly lower than that in the chronic non-atrophic gastritis group, chronic atrophic Gastritis group, and gastric ulcer group (p < 0.05). The H. pylori positive rates in the chronic atrophic gastritis group and gastric cancer group were higher than those in the chronic non-atrophic gastritis group and gastric ulcer Group (p < 0.05). CONCLUSIONS: Serological gastric biopsy is closely correlated to gastric mucosal disease and can be used as a Screening tool in gastric disease.


Assuntos
Anticorpos Antibacterianos/sangue , Biomarcadores/sangue , Mucosa Gástrica/metabolismo , Gastrinas/sangue , Pepsinogênio A/sangue , Neoplasias Gástricas/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antibacterianos/imunologia , Biópsia , Feminino , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Infecções por Helicobacter/sangue , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/microbiologia , Helicobacter pylori/imunologia , Helicobacter pylori/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Neoplasias Gástricas/patologia , Adulto Jovem
10.
BMC Surg ; 19(1): 114, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31429742

RESUMO

BACKGROUND: In gastrectomy, postoperative elevation of C-reactive protein (CRP) is thought to be useful for predicting complications. Laparoscopic gastrectomy (LG) is less invasive than laparotomy and the elevation of CRP is also mild. Postoperative complications such as anastomotic leakage not only increase the severity of the condition, but also carry a poor prognosis when treatment is delayed. Early treatment is therefore necessary. METHOD: This retrospective study examined the relationship between occurrence of complications and the ratio of CRP levels on postoperative days 1 and 3 (CRP ratio) for 449 gastric cancer patients who underwent LG in the Department of Gastrointestinal Surgery at Osaka City University Hospital between 2006 and 2016. RESULTS: We observed that factors associated with postoperative complications were preoperative renal failure and CRP ratio. No significant associations with surgical procedure, operation time, bleeding volume, age, obesity, measured CRP concentration, or white blood cell count were evident. The optimal cut-off for CRP ratio to predict postoperative complications from the receiver operating characteristic curve was 2.13. CONCLUSION: Our results suggested that the risk of severe postoperative complications after LG could be predicted using the CRP ratio.


Assuntos
Proteína C-Reativa/metabolismo , Gastrectomia/efeitos adversos , Laparoscopia/efeitos adversos , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Feminino , Gastrectomia/métodos , Humanos , Laparoscopia/métodos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Curva ROC , Insuficiência Renal/complicações , Estudos Retrospectivos , Neoplasias Gástricas/sangue , Neoplasias Gástricas/complicações
11.
Yonsei Med J ; 60(8): 713-719, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31347325

RESUMO

PURPOSE: We aimed to evaluate the clinical significance of a disintegrin and metalloproteinase 8 (ADAM 8) as a potential blood biomarker for gastric cancer (GC). MATERIALS AND METHODS: Blood ADAM 8 was measured by ELISA. Cytokines/chemokines [interleukin-23 (IL-23), stromal cell-derived factor 1α/CXC chemokine ligand 12 (SDF-1α/CXCL12), interleukin-8 (IL-8), and soluble CD40 ligand (sCD40L)] were measured by chemiluminescent immunoassay. They were compared among five groups; normal/gastritis, high-risk, early GC (EGC), advanced GC (AGC) without distant metastasis, and AGC with distant metastasis by one-way analysis of variance in both training (n=80) and validation dataset (n=241). Clinicopathological features of GC and GC-associated cytokines were evaluated for their correlations with blood ADAM 8. To evaluate the diagnostic accuracy to predict GC, receiver operating characteristic (ROC) curve and logistic regression were used. RESULTS: Blood ADAM 8 significantly increased along GC carcinogenesis in both training (ANOVA, p<0.001) and validation dataset (p<0.001). It was significantly higher in EGC compared to high-risk (post-hoc Bonferroni, p=0.041) and normal (p<0.001). It was also higher in AGC compared with high-risk (p<0.001) and normal (p<0.001) groups. However, no significant difference was found between cancer groups. Blood ADAM 8 was correlated with N-stage (Spearman's correlation, γs=0.320, p=0.011), but not with T-stage or M-stage. Pearson's correlations showed blood ADAM 8 was closely correlated with pre-inflammatory cytokines, IL-23 (p=0.036) and SDF-1α/CXCL12 (p=0.037); however, it was not correlated with pro-angiogenic cytokine IL-8 (p=0.313), and sCD40L (p=0.702). ROC curve and logistic regression demonstrated that blood ADAM 8 showed higher diagnostic accuracy (sensitivity, 73.7%; specificity, 86.2%) than CEA (sensitivity, 23.1%; specificity, 91.4%). Combination of ADAM 8 and CEA further increased the diagnostic accuracy to predict GC (sensitivity, 81.8%; specificity, 84.0%). CONCLUSION: Blood ADAM 8 is a promising biomarker for early detection of GC.


Assuntos
Proteínas ADAM/sangue , Biomarcadores Tumorais/sangue , Detecção Precoce de Câncer , Proteínas de Membrana/sangue , Neoplasias Gástricas/sangue , Neoplasias Gástricas/diagnóstico , Área Sob a Curva , Antígeno Carcinoembrionário/sangue , Citocinas/sangue , Feminino , Humanos , Modelos Logísticos , Masculino , Estadiamento de Neoplasias , Curva ROC , Reprodutibilidade dos Testes , Neoplasias Gástricas/patologia
12.
Yonsei Med J ; 60(8): 720-726, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31347326

RESUMO

PURPOSE: The purpose of this study was to explore the potential early diagnostic value of serum microRNA-381(miRNA-381) in patients with gastric cancer (GC). MATERIALS AND METHODS: Patients with advanced gastric cancer (AGC) and early gastric cancer (EGC), as well as healthy individuals, were enrolled in this study. Expression of miRNA-381 in serum was detected using real-time quantitative PCR. Electrochemiluminescence analysis was used to investigate the expression of classic tumor markers, including carbohydrate antigen (CA) 199, CA724, and carcinoembryonic antigen. Finally, receiver operating characteristic curve and Kaplan-Meier analysis were used to determine the value of miRNA-381 in clinical diagnosis of GC. RESULTS: miRNA-381 was differentially expressed among the study groups. AUC analysis showed that the sensitivity and specificity of serum miRNA-381 in the diagnosis of GC were superior to those of other tumor markers. Furthermore, low levels of miRNA-381 expression were positively correlated with lymph node metastasis and AGC. Finally, Kaplan-Meier survival analysis showed that down-regulation of miRNA-381 was associated with lymph node metastasis and the development of GC. CONCLUSION: miRNA381, which was down-regulated in GC, might be a novel early diagnosis marker for patients with GC.


Assuntos
Biomarcadores Tumorais/sangue , Detecção Precoce de Câncer , MicroRNAs/sangue , Neoplasias Gástricas/sangue , Neoplasias Gástricas/diagnóstico , Área Sob a Curva , Antígeno Carcinoembrionário/sangue , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Curva ROC , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia
13.
Talanta ; 204: 826-832, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31357371

RESUMO

The importance of blood serum testing in most medical diagnosis has led researchers to seek for a reliable analysis method. Raman spectroscopy is a potential tool for probing serum components due to its real-time and non-destructive measurements without need to any additional reagents. So, Raman spectroscopy for the analysis and discrimination of human serum of healthy and gastric cancer subjects is investigated in this work. In order to find the correlation between Raman spectra and enzymatic test results of glucose, cholesterol, HDL, LDL and triglycerides of serum samples, the partial least squares regression (PLSR) method is utilized. Moreover, the Raman spectroscopy is used to distinguish between serum samples of healthy people and gastric cancer patients using partial least square discriminant analysis (PLS-DA) method. Correlation results reveal that for all serum components, the correlation coefficients between Raman spectra and all enzymatic test results are above 94% significantly. Discrimination results of healthy subjects and gastric cancer patients show that 87.5 ±â€¯2.5% of healthy and gastric cancer subjects are diagnosed properly. Our preliminary results can confirm the Raman method in analysis of serum and also as a diagnostic tool in screening of gastric cancer.


Assuntos
Soro/química , Neoplasias Gástricas/diagnóstico , Adulto , Análise Química do Sangue/métodos , Glicemia/análise , Colesterol/sangue , Análise Discriminante , Feminino , Humanos , Lipoproteínas HDL/sangue , Lipoproteínas LDL/sangue , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Análise Espectral Raman/métodos , Neoplasias Gástricas/sangue , Triglicerídeos/sangue
14.
EBioMedicine ; 44: 322-333, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31151932

RESUMO

BACKGROUND: Gastric cancer (GC) is the third leading cause of cancer death. Early detection is a key factor to reduce its mortality. METHODS: We retrospectively collected pre- and postoperative serum samples as well as tumour tissues and adjacent normal tissues from 100 GC patients. Serum samples from non-cancerous patients were served as controls (n = 50). A high-throughput protein detection technology, multiplex proximity extension assays (PEA), was applied to measure levels of over 300 proteins. Alteration of each protein was analysed by univariate analysis. Elastic-net logistic regression was performed to select serum proteins into the diagnostic model. FINDINGS: We identified 19 serum proteins (CEACAM5, CA9, MSLN, CCL20, SCF, TGF-alpha, MMP-1, MMP-10, IGF-1, CDCP1, PPIA, DDAH-1, HMOX-1, FLI1, IL-7, ZBTB-17, APBB1IP, KAZALD-1, and ADAMTS-15) that together distinguish GC cases from controls with a diagnostic sensitivity of 93%, specificity of 100%, and area under receiver operating characteristic curve (AUC) of 0·99 (95% CI: 0·98-1). Moreover, the 19-serum protein signature provided an increased diagnostic capacity in patients at TNM I-II stage (sensitivity 89%, specificity 100%, AUC 0·99) and in patients with high microsatellite instability (MSI) (91%, 98%, and 0·99) compared to individual proteins. These promising results will inspire a large-scale independent cohort study to be pursued for validating the proposed protein signature. INTERPRETATION: Based on targeted proteomics and elastic-net logistic regression, we identified a 19-serum protein signature which could contribute to clinical GC diagnosis, especially for patients at early stage and those with high MSI. FUND: This study was supported by a European H2020-Marie Sklodowska-Curie Innovative Training Networks grant (316,929, GastricGlycoExplorer). Funder had no influence on trial design, data evaluation, and interpretation.


Assuntos
Biomarcadores Tumorais , Proteínas Sanguíneas , Proteoma , Proteômica , Neoplasias Gástricas/sangue , Neoplasias Gástricas/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biologia Computacional/métodos , Detecção Precoce de Câncer , Feminino , Humanos , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Proteômica/métodos , Curva ROC , Neoplasias Gástricas/genética , Neoplasias Gástricas/cirurgia
15.
J Clin Pathol ; 72(12): 825-829, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31235543

RESUMO

AIMS: Aim was to assess the feasibility of serum markers to identify individuals at risk for gastro-oesophageal adenocarcinoma to reduce the number of individuals requiring invasive assessment by endoscopy. METHODS: Blood samples from 56 patients with Barrett's oesophagus and 202 non-Barrett controls who previously took part in a trial assessing the accuracy of the Cytosponge for Barrett's oesophagus were assessed for serum pepsinogen (PG) 1 and 2, gastrin-17, trefoil factor 3 (TFF3) and Helicobacter pylori infection. RESULTS: PG1 was pathological (<50 ng/mL) in 26 patients (10.1%), none of whom had Barrett's oesophagus (p<0.001). Smoking and drinking had no influence on these results. Pathological PG1 was associated with stomach pain (p=0.029), disruption of sleep (p=0.027) and disruption of diet by symptoms (p=0.019). Serum TFF3 was not associated with any clinical parameter. CONCLUSIONS: Assessment of serum PG1 could be combined with a test for Barrett's oesophagus to identify additional patients requiring endoscopy.


Assuntos
Adenocarcinoma/sangue , Esôfago de Barrett/sangue , Biomarcadores Tumorais/sangue , Detecção Precoce de Câncer/métodos , Neoplasias Esofágicas/sangue , Testes Sorológicos , Manejo de Espécimes , Neoplasias Gástricas/sangue , Adenocarcinoma/epidemiologia , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Esôfago de Barrett/epidemiologia , Esôfago de Barrett/patologia , Estudos de Casos e Controles , Detecção Precoce de Câncer/instrumentação , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/patologia , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pepsinogênio A/sangue , Pepsinogênio C/sangue , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Manejo de Espécimes/instrumentação , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/patologia , Fator Trefoil-3/análise , Adulto Jovem
16.
Biomol Concepts ; 10(1): 82-90, 2019 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-31188744

RESUMO

Purpose We aimed to determine optimal cut-off points of plasma levels of ghrelin and serum levels of pepsinogen I, II, and their ratio for screening of gastric cancer (GC). Methods Blood samples were taken from 41 patients with confirmed gastric cancer along with 82 patients without malignancy. Serum levels of pepsinogen I and II, plus plasma levels of acylated ghrelin were measured using commercial ELISA kits. Results The case group had significant lower plasma levels of ghrelin, pepsinogen I, and pepsinogen I/II ratio in comparison to the control group (P<0.001). In the control group, there was significant higher serum pepsinogen I (P=0.028) and pepsinogen II (P=0.003) and lower pepsinogen I/II ratio (P=0.020) in males versus females; significantly higher serum pepsinogen II (P=0.047) and lower pepsinogen I/II ratio (P=0.030) in overweight compared to normal weight patients; and significantly lower pepsinogen I/II ratio (P=0.030) in smokers versus non-smoker. In the case group, there was only significantly lower pepsinogen I (P=0.006) in males versus females, and significantly lower plasma ghrelin (P=0.017) in overweight compared to normal weight patients. The characteristic curve analysis indicated that pepsinogen I at a cut-off of 70.95 µg/L and pepsinogen I/II ratio at cut-off of 2.99, had good sensitivity and specificity. Conclusions Just serums levels of pepsinogen I and the ratio of pepsinogen I/II can be used as biomarker to screen GC.


Assuntos
Biomarcadores Tumorais/sangue , Pepsinogênios/sangue , Neoplasias Gástricas/sangue , Adulto , Idoso , Biomarcadores Tumorais/normas , Estudos de Casos e Controles , Feminino , Grelina/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Pepsinogênios/normas , Sensibilidade e Especificidade
17.
Anticancer Res ; 39(6): 3121-3130, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31177157

RESUMO

BACKGROUND/AIM: The aim of the current study was to investigate the impact of the preoperative red cell distribution width (RDW) value on the overall survival (OS) and cancer-specific survival (CSS) of gastric cancer patients. PATIENTS AND METHODS: A total of 366 gastric cancer patients who underwent curative gastrectomy were retrospectively reviewed. Among them, RDW was evaluated in 165 non-elderly and 201 elderly patients. RESULTS: Multivariate analysis revealed that pathological stage (pStage), RDW, and carcinoembryonic antigen (CEA), were independent prognostic factors of OS, while pStage and RDW were independent prognostic factors of CSS. In non-elderly patients, based on the multivariate analysis, pStage, adjuvant chemotherapy, and RDW were identified as independent prognostic factors of OS. In elderly patients, RDW was identified as independent prognostic factors of OS and CSS. CONCLUSION: Preoperative RDW is a promising independent prognostic factor in gastric cancer.


Assuntos
Adenocarcinoma/sangue , Adenocarcinoma/cirurgia , Índices de Eritrócitos , Eritrócitos , Gastrectomia , Laparoscopia , Neoplasias Gástricas/sangue , Neoplasias Gástricas/cirurgia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Progressão da Doença , Feminino , Gastrectomia/efeitos adversos , Gastrectomia/métodos , Gastrectomia/mortalidade , Humanos , Laparoscopia/efeitos adversos , Laparoscopia/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Intervalo Livre de Progressão , Estudos Retrospectivos , Fatores de Risco , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Fatores de Tempo , Adulto Jovem
18.
World J Gastroenterol ; 25(22): 2763-2775, 2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31235999

RESUMO

BACKGROUND: Gastric cancer (GC) is the fourth most frequent malignancy all over the world. The diagnosis of GC is challenging and the prognosis of GC is very unfavorable. Accumulating evidence reveals that serum long noncoding RNAs (lncRNAs) can function as biomarkers in various types of cancers, including GC. AIM: To explore the level and molecular mechanism of the lncRNA HOXA11-AS in GC and the diagnostic and prognostic significance of serum HOXA11-AS in GC. METHODS: HOXA11-AS levels in GC tissue, cell lines, and serum samples were measured. The correlation between HOXA11-AS expression and clinicopathological characteristics was analyzed. The role of HOXA11-AS in the diagnosis and prognosis of GC was evaluated. Cell function assays were performed for exploration of the roles of HOXA11-AS in GC cells. Moreover, Western blot was performed to explore the target regulated by HOXA11-AS in GC cells. RESULTS: Up-regulation of HOXA11-AS was found in GC tissues, cell lines, and serum samples. In GC patients, decreased serum HOXA11-AS levels were negatively related with tumor size, TNM stage, and lymph node metastasis. The area under the receiver operating characteristic curve of serum HOXA11-AS in the diagnosis of GC was 0.924 (95%CI: 0.881-0.967; sensitivity, 0.787; specificity 0.978). Results of the Kaplan-Meier survival curves suggested the GC patients with a lower HOXA11-AS level having a better overall survival rate. HOXA11-AS promoted GC cell proliferation and invasion. SRSF1 may be the target regulated by HOXA11-AS in GC cells. CONCLUSION: HOXA11-AS promotes GC cell proliferation and invasion via SRSF1 and may function as a promising marker in GC.


Assuntos
Biomarcadores Tumorais/metabolismo , Ácidos Nucleicos Livres/metabolismo , RNA Longo não Codificante/metabolismo , Fatores de Processamento de Serina-Arginina/genética , Neoplasias Gástricas/genética , Adulto , Idoso , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Ácidos Nucleicos Livres/sangue , Feminino , Regulação Neoplásica da Expressão Gênica , Voluntários Saudáveis , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Prognóstico , RNA Longo não Codificante/sangue , Estômago/patologia , Neoplasias Gástricas/sangue , Neoplasias Gástricas/mortalidade , Taxa de Sobrevida , Regulação para Cima
19.
World J Surg Oncol ; 17(1): 108, 2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31238937

RESUMO

BACKGROUND: The use of staging laparoscopy (SL) has become widespread in patients with advanced gastric cancer (GC). This study aimed to evaluate the predictive value of the neutrophil/lymphocyte ratio (NLR) for the presence of peritoneal metastasis during staging laparoscopy in patients with advanced GC. METHODS: This retrospective analysis was performed in 35 patients with advanced GC who underwent SL at Kanazawa Medical University Hospital between January 2009 and December 2017. Clinicopathological characteristics were examined and multivariate analyses were performed to identify preoperative laboratory parameters that were independently associated with the presence of peritoneal metastasis or cytological malignancy (P/CY positive) during SL. RESULTS: A P/CY-positive result was confirmed during SL in 16 patients (45.7%). Patients with type 4 or diffuse type 3 tumors showed a significantly higher P/CY-positive rate than those with other tumor types (58.3% vs. 18.2%, P = 0.02). In the univariate analysis for preoperative laboratory parameters, NLR (P < 0.0001) and total protein (P = 0.03) and albumin (P = 0.04) levels were significantly correlated with a P/CY-positive result. On multivariate analysis, NLR was significantly correlated with a P/CY-positive result (P = 0.0002). In patients with type 4 or diffuse type 3 tumors, a high NLR (> 3.5) was associated with a significantly higher P/CY-positive rate than a low NLR (≤ 3.5) (83.3% vs. 33.3%, P = 0.01). Moreover, in patients without type 4 or diffuse type 3 tumors, the P/CY-positive rates were 100% and 0% in patients with NLR > 3.5 and NLR ≤ 3.5, respectively. CONCLUSIONS: The preoperative NLR was a significant independent predictor of the presence of peritoneal metastasis during SL. Regardless of tumor type, patients with a high NLR could be reasonable candidates for SL. On the other hand, non-diffuse type tumor accompanied by a low NLR may not need to undergo SL.


Assuntos
Laparoscopia/métodos , Linfócitos , Neutrófilos , Neoplasias Peritoneais/diagnóstico , Neoplasias Gástricas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Peritoneais/sangue , Neoplasias Peritoneais/secundário , Peritônio/diagnóstico por imagem , Valor Preditivo dos Testes , Período Pré-Operatório , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/sangue
20.
Cancer Sci ; 110(9): 2875-2883, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31254422

RESUMO

Previous studies have shown sex-related differences in the incidence of adverse events following treatment with fluoropyrimidines, however the mechanism of this difference is unknown. We examined sex-related differences in the safety of S-1 plus oxaliplatin (SOX) and S-1 plus cisplatin (CS) in 663 metastatic gastric cancer patients taking part in a phase III study. The incidences of leukopenia (odds ratio [OR] 1.9; P = .015), neutropenia (OR 2.2; P = .002), nausea (OR 2.0; P = .009), and vomiting (OR 2.8; P < .001) were increased in women versus men treated with SOX, while vomiting (OR 2.9; P < .001) and stomatitis (OR 1.8; P = .043) were increased in women versus men treated with CS. In contrast, male patients treated with CS experienced thrombocytopenia more often (OR 0.51; P = .009). The mean relative dose intensity of S-1 in SOX was 75.4% in women and 81.4% in men (P = .032). No difference in efficacy was observed between women and men undergoing either regimen. Sex-related differences in adverse reactions during SOX and CS treatment were confirmed in this phase III study. Further translational research studies are warranted to pursue the cause of this difference.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/efeitos adversos , Oxaliplatina/efeitos adversos , Ácido Oxônico/efeitos adversos , Neoplasias Gástricas/tratamento farmacológico , Tegafur/efeitos adversos , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Cisplatino/administração & dosagem , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Náusea/epidemiologia , Neutropenia/induzido quimicamente , Neutropenia/epidemiologia , Oxaliplatina/administração & dosagem , Ácido Oxônico/administração & dosagem , Fatores Sexuais , Neoplasias Gástricas/sangue , Neoplasias Gástricas/patologia , Estomatite/induzido quimicamente , Estomatite/epidemiologia , Tegafur/administração & dosagem , Trombocitopenia/induzido quimicamente , Trombocitopenia/epidemiologia , Vômito/induzido quimicamente , Vômito/epidemiologia
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