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1.
J Cancer Res Clin Oncol ; 145(9): 2285-2292, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31372722

RESUMO

BACKGROUND: The cell adhesion molecule close homologue of L1 (CHL1) is a potential tumour suppressor and was recently detected in non-small cell lung cancer (NSCLC) specimens. The expression pattern, prognostic, and functional role of CHL1 in NSCLCs is unknown. METHODS: We evaluated the protein expression of CHL1 by immunohistochemistry in 2161 NSCLC patients based on a tissue microarray. The results were correlated with clinical, histopathological, and patient survival data (Chi square test, t test, and log-rank test, respectively). A multivariate analysis (Cox regression) was performed to validate its impact on patients' survival. RESULTS: CHL1 was expressed in NSCLC patients and was significantly overexpressed in lung adenocarcinomas and squamous cell carcinomas compared to neuroendocrine and large cell carcinomas of the lung (p < 0.001). CHL1 expression was associated with the T stage in adenocarcinomas (p = 0.011) and with metastatic lymph node status and UICC stage in squamous cell carcinomas (p = 0.034 and p = 0.035, respectively). Increased CHL1 expression was associated with improved survival in univariate (p = 0.031) and multivariate analyses (odds ratio 0.797, 95% confidence interval 0.677-0.939, p = 0.007). CONCLUSION: The prognostic significance of CHL1 makes it a potential prognostic and therapeutic target and underlines its role as a tumour suppressor. Further validation studies and functional analyses are needed to investigate its potential role in tumourigenesis and dissemination.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Moléculas de Adesão Celular/metabolismo , Neoplasias Pulmonares/mortalidade , Adenocarcinoma/diagnóstico , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Idoso , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Análise de Sobrevida , Análise Serial de Tecidos
2.
J Cancer Res Clin Oncol ; 145(9): 2251-2259, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31385026

RESUMO

PURPOSE: Fibroblast Growth Factor Receptor 4 (FGFR4) was proposed to hold prognostic significance in high-grade serous ovarian carcinoma (HGSOC). However, information on this deriving from large, representative patient panels is still missing, though such data would be indispensable to validate suitability of FGFR4 as prognostic marker or even pharmacological target. METHODS: 1063 ovarian cancer cases were included in this study. Immunohistochemistry (IHC) was performed using two different anti-FGFR4 specific antibodies (HPA027273, sc-124) on an automated staining system. IHC data of both FGFR4 antibodies were available from 995 cases. FGFR4 immunostaining was correlated to prognostic factors including survival using uni- and multivariate proportional hazard models. RESULTS: FGFR4 was positively associated with advanced FIGO stage, high grade and presence of residual disease. When progression free (PFS) of FGFR4 negative vs. positive patients was compared, patients scored as FGFR4 positive had significantly shortened PFS as compared to those that stained negative. All associations of FGFR4 and shortened PFS were lost during multivariate testing. No significant associations were found in terms of OS. CONCLUSIONS: We were not able to confirm FGFR4 as an independent negative prognosticator as described before. However, FGFR4 was highly prevalent in those cases harboring residual disease after debulking surgery. Since especially patients that could only be debulked sub-optimally may benefit from targeted adjuvant treatment, tyrosine kinase inhibitors targeting FGFRs might turn out to be an interesting future treatment option.


Assuntos
Cistadenocarcinoma Seroso/diagnóstico , Cistadenocarcinoma Seroso/cirurgia , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/cirurgia , Receptor Tipo 4 de Fator de Crescimento de Fibroblastos/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Cistadenocarcinoma Seroso/metabolismo , Cistadenocarcinoma Seroso/patologia , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Neoplasia Residual , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Período Pós-Operatório , Prognóstico , Estudos Retrospectivos , Análise Serial de Tecidos , Resultado do Tratamento
3.
Medicine (Baltimore) ; 98(33): e16711, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415363

RESUMO

BACKGROUND: Multiple myeloma (MM) is a clonal plasma cell malignancy associated with hypercalcemia, bone lesions, and renal failure. The prognostic significance of the mutation of miRNAs, one kind of small noncoding RNA molecules that can modulate gene expression, should be confirmed in non-Hodgkin lymphomas (NHL). This study aimed to identify the prognostic value of miRNAs in patients with MM. METHODS: A meta-analysis was performed to estimate the pooled hazard ratios and their corresponding 95% confidence intervals for the associations between levels of miRNA expression (predictive factors) and outcomes in patients with MM. We systematically searched the PubMed, Web of Science, and China National Knowledge Infrastructure databases (final search conducted January 1, 2018) to identify eligible studies. Eligible studies were included by certain inclusion and exclusion criteria, whose quality was assessed by Newcastle-Ottawa Scale. RESULTS: After performing the literature search and review, 10 relevant studies, including 1214 cases, were identified. The results of our meta-analysis revealed that upregulated miR-92a level and downregulated miR-16, miR-25, miR-744, miR-15a, let-7e, and miR-19b expression were associated with poor prognosis in MM. CONCLUSIONS: This study identified miRNAs could serve as potential prognostic biomarkers in MM. Given the limited research available, the clinical application of these findings has yet to be verified.


Assuntos
MicroRNAs/metabolismo , Mieloma Múltiplo/genética , Biomarcadores Tumorais/metabolismo , Regulação para Baixo , Feminino , Expressão Gênica , Humanos , Masculino , Mutação , Prognóstico , Modelos de Riscos Proporcionais , Regulação para Cima
4.
Gene ; 716: 144025, 2019 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-31394177

RESUMO

BACKGROUND: Existing meta-analysis have shown that the miR-200 family can be taken as a prognostic biomarker for many tumors. However, great heterogeneity was shown in predicting overall survival (OS) and progression-free survival (PFS). Emerging studies indicate that the expression levels of members of the miR-200 family are tissue-specific among various tumor tissues, which may be the main reason of the heterogeneity in predicting survival prognosis of tumor patients with the miR-200 family as biomarkers. By further analysis of heterogeneity of the miR-200 family as a biomarker for predicting survival prognosis of patients with different tumors, we expected to provide an accurate basis for the clinical application of the miR-200 family to predict the prognosis of patients with different tumors. METHODS: Eligible published studies were identified by searching the databases of PubMed, Embase and Web of Science. The clinical data of patients in the studies were pooled, and pooled hazard ratios (HR) with 95% confidence intervals (95% CI) were used to calculate the strength of this association. The expressions of miRNAs were extracted from The Cancer Genome Atlas (TCGA). We presented the expressions of each member in miR-200 family in 15 types of cancer by boxplot, and analyzed the correlation among the members of miR-200 family by Spearman method. Different subgroup analyses were then performed based on the correlation among the members of miR-200 family, and the publication bias was assessed using the funnel plot of the Egger bias indicator test. RESULTS: Of 36 articles, including 15 tumor types and 4644 patients were included to perform meta-analysis. It was found that miR-200 family members can be used as independent protective factors in patients with various tumors but the miR-200 family has a higher heterogeneity in predicting prognosis: OS (HR = 0.82, 95% CI: 0.66-1.03, I2 = 85%, P < 0.01) and PFS (HR = 0.81, 95% CI: 0.57-1.16, I2 = 97%, P < 0.01). The data from TCGA database were used to analyze the expression levels of the miR-200 family and the results showed that the expression of miR-429 in different cancers is very different, and there are significant differences in expression levels compared with other miR-200 family members; the expression levels of miR-200a and miR-200b in various tumor tissues were similar to each other, respectively; miR-200c and miR-141 showed similar expression levels in each of most types of cancer tissues except ovarian cancer (OC). The expression levels of members of the miR-200 family in breast cancer (BRCA), cervical cancer (CESC), colon cancer (COAD), esophageal cancer (ESCA), head and neck cancer (HNSC), lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) are relatively stable, but great variations can be found in the expression levels of miR-200 family members in ovarian cancer (OC), liver cancer (LIHC), renal clear cell carcinoma (KIRC) and renal papillary cell carcinoma (KIRP). Cluster analysis of expression of target genes of miR-200 family in different cancers yielded similar results to the expression level of the miR-200 family. Subgroup analysis of OC, LIHC, GC and LUAD based on expression levels and clustering results reduced or even eliminated the heterogeneity of miR-200 family members in predicting patient outcomes. CONCLUSIONS: Our results convincingly demonstrated that the miR-200 family could serve as a prognostic biomarker for cancers mentioned above and has potential value in clinical practice. MiR-200 family as prognostic biomarkers needs to be performed according to different tumor tissues and correlation between members in miR-200 family.


Assuntos
MicroRNAs/metabolismo , Neoplasias/mortalidade , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Mineração de Dados , Humanos , Neoplasias/genética , Neoplasias/metabolismo , Prognóstico , Análise de Sobrevida
5.
Biol Res ; 52(1): 42, 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31399040

RESUMO

BACKGROUND: Prognosis remains one of most crucial determinants of gastric cancer (GC) treatment, but current methods do not predict prognosis accurately. Identification of additional biomarkers is urgently required to identify patients at risk of poor prognoses. METHODS: Tissue microarrays were used to measure expression of nine GC-associated proteins in GC tissue and normal gastric tissue samples. Hierarchical cluster analysis of microarray data and feature selection for factors associated with survival were performed. Based on these data, prognostic scoring models were established to predict clinical outcomes. Finally, ingenuity pathway analysis (IPA) was used to identify a biological GC network. RESULTS: Eight proteins were upregulated in GC tissues versus normal gastric tissues. Hierarchical cluster analysis and feature selection showed that overall survival was worse in cyclin dependent kinase (CDK)2, Akt1, X-linked inhibitor of apoptosis protein (XIAP), Notch4, and phosphorylated (p)-protein kinase C (PKC) α/ß2 immunopositive patients than in patients that were immunonegative for these proteins. Risk score models based on these five proteins and clinicopathological characteristics were established to determine prognoses of GC patients. These proteins were found to be involved in cancer related-signaling pathways and upstream regulators were identified. CONCLUSION: This study identified proteins that can be used as clinical biomarkers and established a risk score model based on these proteins and clinicopathological characteristics to assess GC prognosis.


Assuntos
Biomarcadores Tumorais/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias Gástricas/mortalidade , Idoso , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Análise de Sobrevida , Análise Serial de Tecidos
7.
Urol Clin North Am ; 46(3): 353-362, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31277730

RESUMO

Experience demonstrates multiple paths to cure for patients with clinical stage I testicular cancer. Because all options should provide a long-term disease-free rate near 100%, overall survival is no longer relevant in decision making, allowing practitioners to factor in quality of life, toxicity, cost, and impact on compliance. Surveillance for clinical stage I seminoma and clinical stage I nonseminoma has become the preferred option. The contrarian view is that a risk-adapted approach should persist, with surveillance for low-risk individuals and active therapy high-risk individuals. However, results obtained in unselected patients provide a strong argument against the need for such an approach.


Assuntos
Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Embrionárias de Células Germinativas/terapia , Neoplasias Testiculares/patologia , Neoplasias Testiculares/terapia , Biomarcadores Tumorais/metabolismo , Intervalo Livre de Doença , Custos de Cuidados de Saúde , Humanos , Masculino , Estadiamento de Neoplasias , Qualidade de Vida
8.
Tumour Biol ; 41(7): 1010428319860728, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31264534

RESUMO

Colon cancer represents one of the most common cancers in the world. Despite improved treatment, mortality remains high. In order to improve the assessment of prognosis for colon cancer patients, identifying new prognostic markers remains necessary. We analyzed preoperative serum samples from 148 colon cancer patients surgically treated at Helsinki University Hospital from 1998 through 2002 using a multiplex proximity extension assay (Oncology II panel, Olink Bioscience, Uppsala, Sweden), a panel constituting 92 immunological and oncological markers. We performed univariate and multivariate analyses on these patients and calculated the disease-specific survival among patients using the log-rank test for Kaplan-Meier estimates. In the univariate survival analysis of 92 biomarkers, 26 resulted in p < 0.1. Among these, eight biomarkers emerged as statistically significant (p < 0.05). Patients with low levels of kallikrein 13 had a poor prognosis. Moreover, patients with high levels of amphiregulin, carcinoembryonic antigen-related adhesion molecule 5, interleukin 6, mucin 16, syndecan 1, transforming growth factor alpha, and vimentin also had a poor prognosis. In the multivariate analysis, kallikrein 13 and mucin 16 emerged as independent prognostic markers. The role of kallikrein 13, a member of the serine protease kallikrein biomarker family, in tumorigenesis remains unclear. Mucin 16 is also known as carbohydrate antigen 125, a well-known ovarian cancer biomarker. Patients with low levels of kallikrein 13 (hazard ratio: 0.36; 95% confidence interval: 0.14-0.92; p = 0.033) and high levels of mucin 16 (hazard ratio: 3.15; 95% confidence interval: 1.68-5.93; p < 0.005) had a poor prognosis. Mucin 16 and kallikrein 13 represent independent prognostic markers for colon cancer. Furthermore, the clinical utility of mucin 16 and kallikrein 13 serum tests warrants additional investigation.


Assuntos
Antígeno Ca-125/metabolismo , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Calicreínas/metabolismo , Proteínas de Membrana/metabolismo , Idoso , Biomarcadores Tumorais/metabolismo , Feminino , Humanos , Imunoensaio/métodos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Análise de Sobrevida
9.
Medicine (Baltimore) ; 98(26): e15872, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261495

RESUMO

Human epidermal growth factor receptor 2-positive (HER2+) breast cancer accounts for ∼20% of invasive breast cancers and is associated with poor prognostics. The recent outcome of HER2+ breast cancer treatment has been vastly improved owing to the application of antibody-targeted therapies. Trastuzumab (Herceptin) is a monoclonal antibody designed to target HER2+ breast cancer cells. In addition to improved survival in the adjuvant treatment of HER2+ breast cancer, trastuzumab treatment has also been associated with cardiotoxicity side effect. However, the molecular mechanisms of trastuzumab action and trastuzumab-mediated cardiotoxicity are still not fully understood. Previous research utilized bulk transcriptomics analysis to study the underlining mechanisms, which relied on averaging molecular signals from bulk tumor samples and might have overlooked key expression features within breast cancer tumor. In contrast to previous research, we compared the single cancer cell level transcriptome profile between trastuzumab-treated and nontreated patients to reveal a more in-depth transcriptome profile. A total of 461 significantly differential expressed genes were identified, including previously defined and novel gene expression signatures. In addition, we found that trastuzumab-enhanced MGP gene expression could be used as prognostics marker for longer patient survival in breast invasive carcinoma patients, and validated our finding using TCGA (The Cancer Genome Atlas) breast cancer dataset. Moreover, our study revealed a 48-gene expression signature that is associated with cell death of cardiomyocytes, which could be used as early biomarkers for trastuzumab-mediated cardiotoxicity. This work is the first study to look at single cell level transcriptome profile of trastuzumab-treated patients, providing a new understanding of the molecular mechanism(s) of trastuzumab action and trastuzumab-induced cardiotoxicity side effects.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Receptor ErbB-2/metabolismo , Transcriptoma/efeitos dos fármacos , Trastuzumab/uso terapêutico , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/epidemiologia , Proteínas de Ligação ao Cálcio/metabolismo , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/epidemiologia , Carcinoma Ductal de Mama/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Feminino , Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Projetos Piloto , Prognóstico , RNA Mensageiro/metabolismo , Análise de Sequência de RNA , Análise de Célula Única , Análise de Sobrevida
10.
Medicine (Baltimore) ; 98(26): e15954, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261501

RESUMO

Early diagnosis of pancreatic cancer (PC) is based on endoscopic ultrasound (EUS). However, EUS is invasive and requires a high level of technical skill. Recently, liquid biopsies have achieved the same sensitivity and specificity for the diagnosis of numerous pathologies, including cancer. Insulin-promoting factor 1 (PDX1) and Msh-homeobox 2 (MSX2), 2 homeotic genes, have been confirmed to be related to pancreatic oncogenesis.The aim of this study is to establish the diagnostic utility of circulating serum levels of MSX2 and PDX1 expression in patients with PC.A prospective study was conducted from January 2014 to February 2017. Patients with a suspected diagnosis of PC who underwent fine needle aspiration biopsy guided by EUS (EUS-FNA) were included in the study, in addition to non-PC control subjects. Both tissue and blood serum samples were submitted to histopathological analysis and measurement of PDX1 and MSX2 gene expression by means of qRT-PCR.Patients were divided into non-PC, malignant pathology (MP), or benign pathology (BP) groups. Significant differences in both MSX2 [2.05 (1.66-4.60) vs 0.83 (0.49-1.60), P = .006] and PDX1 [2.59 (1.28-10.12) vs 1.02 (0.81-1.17), P = .036] gene expression were found in blood samples of PC compared with non-PC subjects. We also observed a significant increase in MSX2 transcripts in tissue biopsy samples of patients diagnosed with MP compared with those with BP [1.98 (1.44-4.61) and 0.66 (0.45-1.54), respectively, P = .012]. The ROC curves indicate a sensitivity and specificity of 80% for PDX1 and 86% for MSX2.Gene expression of MSX2 in tissue samples obtained by EUS-FNA and serum expression of MSX2 and PDX1 were higher in patients with PC.


Assuntos
Proteínas de Homeodomínio/metabolismo , Neoplasias Pancreáticas/metabolismo , Transativadores/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Biópsia por Agulha Fina , Estudos de Casos e Controles , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Feminino , Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Pâncreas/metabolismo , Pâncreas/patologia , Neoplasias Pancreáticas/patologia , Estudos Prospectivos , Sensibilidade e Especificidade
11.
Medicine (Baltimore) ; 98(26): e16084, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261522

RESUMO

Heme oxygenase-1 (HO-1) is an important catalytic enzyme in heme degradation, which increases during stressful conditions. It plays a major role in antioxidative and antiapoptotic processes and is associated with tumor growth and metastasis.This study aimed to evaluate the degree of HO-1 expressions in hepatocellular carcinoma (HCC) surgical specimens and the correlation between HO-1 expression and patient prognosis. Formalin-fixed, paraffin-embedded HCC tissue samples (n = 96) were included in the analysis, and the expression of HO-1 was evaluated by immunohistochemical staining. We reviewed clinical features of patients and evaluated the prognostic role of HO-1 in patient survival and recurrence.Positive HO-1 expression was identified in 43 cases (44.8%) and was frequently found in patients with advanced histology (Edmondson-Steiner [E-S] grade 2, 3, 4), α-fetoprotein (AFP) level of more than 200 IU/mL, and the presence of microvascular and capsular invasion (P < .05). In the univariate analysis, the overall survival (OS) and disease-free survival (DFS) of patients with HO-1-positive HCC were not statistically different from those with HO-1-negative HCC. Moreover, HO-1 expression was not associated with patient survival and recurrence based on the multivariate analysis. In the subgroup analysis of patients without preoperative transarterial chemoembolization (TACE) (n = 61), HO-1 was not also associated with tumor recurrence (P = .681).The clinical implication of HO-1 activity is controversial in various malignancies. However, HO-1 expression did not seem to influence the prognosis of HCC patients.


Assuntos
Carcinoma Hepatocelular/enzimologia , Heme Oxigenase-1/metabolismo , Neoplasias Hepáticas/enzimologia , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Feminino , Expressão Gênica , Humanos , Imuno-Histoquímica , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva , Estudos Retrospectivos , Análise de Sobrevida
12.
Medicine (Baltimore) ; 98(26): e16131, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261535

RESUMO

BACKGROUND: The FOS gene is located on human chromosome 14q21-31 and encodes the nuclear oncoprotein c-Fos. This study analyzed the correlation between the FOS noncoding region rs7101 and rs1063169 polymorphisms and colorectal cancer susceptibility and prognosis. METHODS: We analyzed the FOS genotypes in 432 colorectal cancer patients and 315 healthy subjects by PCR/Sanger sequencing. Survival was analyzed by Kaplan-Meier and Cox regression analysis. Western blot was used to detect the expression of c-Fos protein in cancer tissues and adjacent tissues in colorectal cancer patients with different genotypes. RESULTS: The presence of a T allele at rs7101 and a T allele at rs1063169 in FOS carried a higher risk of colorectal cancer [adjusted odds ratio (OR) = 1.237, 95% confidence interval (95% CI) = 1.131-1.346, P ≤ .001 and adjusted OR = 1.218, 95% CI = 1.111-1.327, P ≤ .001, respectively]. c-Fos protein levels were significantly higher in variant cancer tissues than in normal mucosa tissues (P < .05), and c-Fos proteins levels were also higher in homozygous variant cancer tissues than in heterozygous variant cancer tissues. The 3-year survival rate of patients with wild-type FOS was higher than that of patients with variant FOS (P < .05). CONCLUSION: The rs7101 and rs1063169 polymorphisms in the noncoding region of FOS are associated with the risk of developing colorectal cancer and the progression of colorectal cancer, which may be because the mutation enhances the expression of c-Fos protein to promote the incidence and development of colorectal cancer.


Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Progressão da Doença , Feminino , Seguimentos , Expressão Gênica , Interação Gene-Ambiente , Estudos de Associação Genética , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Análise de Sobrevida
13.
Medicine (Baltimore) ; 98(26): e16190, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261557

RESUMO

Biomarkers that predict tumor response before surgical treatment are necessary to help select patients for preoperative chemoradiotherapy for rectal cancer. However, no definite predictive biomarker has been established. This study explored programmed death-ligand 1 (PD-L1), epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), p-signal transducer and activator of transcription 3 (p-STAT3), and death-domain associated protein as predictive biomarkers with regard to preoperative chemoradiotherapy in rectal cancer.Formalin-fixed paraffin-embedded cancer tissues from pretreatment biopsies from 31 patients who underwent preoperative chemoradiotherapy were studied. The biomarkers were evaluated by immunohistochemistry.PD-L1 positivity was found in 22.6% of 31 patients and complete response (CR) showed 33.3% and non-CR showed 18.2%. EGFR positivity was found in 71.0% of 31 patients and CR showed 88.9% and non-CR showed 73.6%. VEGF positivity was found in 83.9% of 31 patients and CR showed 88.9% and non-CR showed 81.8%. p-STAT3 positivity was found in 80.6% of 31 patients and CR showed 88.9% and non-CR showed 77.3%. On multiple logistic regression analysis, only VEGF expression was found to be a significant predictive factor for CR (P = .001). VEGF expression in pretreatment biopsies might be a predictive marker for CR after preoperative chemoradiation in rectal cancer.Although there is a restriction of small sample size, our finding suggested that this study can be foundation for a larger further study for biomarkers which can predict neoadjuvant therapy response of specimens obtained for diagnosis before surgery.


Assuntos
Neoplasias Retais/metabolismo , Neoplasias Retais/terapia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Quimiorradioterapia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Período Pré-Operatório , Prognóstico , Neoplasias Retais/patologia , Estudos Retrospectivos
14.
Medicine (Baltimore) ; 98(26): e16207, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261569

RESUMO

The cell-surface glycoprotein, mesothelin, is normally present on mesothelial cells. Overexpression of mesothelin has been reported in many tumors and is correlated with poor outcome. We investigated the clinicopathologic significance of mesothelin expression in colorectal adenocarcinoma with microsatellites instability (MSI) status.Mesothelin expression was evaluated immunohistochemically in tissue microarray blocks from 390 colorectal adenocarcinoma samples. Mesothelin expression was interpreted according to the intensity and extent. A score of 2 was considered high expression. We analyzed the correlation between mesothelin expression and clinicopathologic characteristics.High mesothelin expression was observed in 177 (45.4%) out of 390 colorectal adenocarcinoma samples and was significantly associated with high histologic grade (P = .037), lymphatic invasion (P = .028), lymph node metastasis (P = .028), and high AJCC stage (P = .026). Kaplan-Meier survival curves revealed no significant difference between patients with high mesothelin expression and patients with low mesothelin expression in both recurrence-free survival (RFS) and cancer-specific survival (P = .609 and P = .167, respectively). In subgroup survival analyses, high mesothelin expression was associated with poor RFS in the MSI-High group of colorectal adenocarcinoma (P = .004).High mesothelin expression was significantly associated with aggressive phenotypes and poor patient outcome in MSI-High colorectal adenocarcinoma.


Assuntos
Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Proteínas Ligadas por GPI/metabolismo , Instabilidade de Microssatélites , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Fenótipo , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Análise Serial de Tecidos
15.
Acta Gastroenterol Belg ; 82(2): 291-299, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31314191

RESUMO

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers worldwide. A non-invasive test, with high sensitivity and specificity is essential for early detection, improved outcome and avoidance of unnecessary invasive tests. This study aims to evaluate the accuracy of the faecal immunochemical testing for haemoglobin (FIT) in the detection of CRC, both in symptomatic and screening population and to summarise the available evidence to date. METHODS: Search strategy was initially developed in MEDLINE and adapted for use in other databases. Studies were included if they had fulfilled the criteria. QUADAS-2 tool was used for quality assessment and data analysis performed using STATA 15 software. RESULTS: A total of 17 out of 92 articles were included in the final analysis. Within the symptomatic group (n= 6755), the overall pooled sensitivity and specificity of FIT to detect CRC was 0.90 (95% CI 0.87-0.92) and 0.87 (95% CI 0.83-0.90) respectively. In the screening population (n=24197), the pooled sensitivity and specificity of FIT to detect CRC was 0.69 (95% CI 0.54-0.81) and 0.94 (95% CI 0.94-0.95) respectively. Most analytics were comparable with cut off less than 20µg/g feces providing optimal sensitivity and specificity for symptomatic and screening populations respectively. CONCLUSION: For the detection of CRC within the screening population, FIT has high specificity and sensitivity. In the symptomatic group, FIT's high sensitivity (90%) supports its role as a triage test to guide the selection of patients who require urgent lower gastrointestinal tract evaluation.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/diagnóstico , Fezes/química , Hemoglobinas/metabolismo , Sangue Oculto , Detecção Precoce de Câncer/métodos , Hemoglobinas/análise , Humanos , Imunoquímica , Programas de Rastreamento/métodos
16.
J Cancer Res Clin Oncol ; 145(9): 2227-2240, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31317325

RESUMO

PURPOSE: Enhancer of zeste homolog 2 (EZH2) is associated with epigenetic gene silencing and aggressiveness in many tumor types. However, the prognostic impact of high EZH2 expression is controversially discussed for colorectal cancer. For this reason, we immunohistochemically analyzed EZH2 expression in 105 specimens from colon cancer patients separately for tumor center and invasion front. METHODS: All sections from tissue microarrays were evaluated manually and digitally using Definiens Tissue Studio software (TSS). To mirror-image the EZH2 status at the tumor invasion front, we treated HCT116 colon cancer cells with the EZH2 inhibitor 3-Deazaneplanocin A (DZNep) and studied the growth of in ovo xenografts in the chorioallantoic membrane (CAM) assay. RESULTS: We showed a significant decrease in EZH2 expression and the repressive H3K27me3 code at the tumor invasion front as supported by the TSS-constructed heatmaps. Loss of EZH2 at tumor invasion front, but not in tumor center was correlated with unfavorable prognosis and more advanced tumor stages. The observed cell cycle arrest in vitro and in vivo was associated with higher tumor aggressiveness. Xenografts formed by DZNep-treated HCT116 cells showed loosely packed tumor masses, infiltrative growth into the CAM, and high vessel density. CONCLUSION: The differences in EZH2 expression between tumor center and invasion front as well as different scoring and cutoff values can most likely explain controversial literature data concerning the prognostic value of EZH2. Epigenetic therapies using EZH2 inhibitors have to be carefully evaluated for each specific tumor type, since alterations in cell differentiation might lead to unfavorable results.


Assuntos
Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Margens de Excisão , Adenocarcinoma/diagnóstico , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Biomarcadores Tumorais/metabolismo , Embrião de Galinha , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/cirurgia , Regulação para Baixo , Feminino , Células HCT116 , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Estudos Retrospectivos , Análise Serial de Tecidos
17.
Medicine (Baltimore) ; 98(27): e16087, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31277104

RESUMO

Plasmacytoma variant translocation 1 (PVT1) is highly expressed in a variety of cancer tissues and is related to the clinicopathological features and prognosis. However, the prognostic value of PVT1 is still controversial. Therefore, this systematic evaluation and meta-analysis were performed to evaluate the relationship between PVT1 expression and clinicopathological features.PubMed, EMBASE, Web of science, and Cochrane library databases were searched for literature collection according to inclusion criteria and exclusion criteria. The pooled hazard ratios (HRs) or odds ratios (ORs) were used to evaluate the association between PVT1 expression and overall survival, tumor size, tumor-node-metastasis (TNM) stage, lymph node metastasis, and distant metastasis.A total of 39 articles including 3974 patients were included in the study. The results showed that the expression of PVT1 was closely related to the overall survival rate of cancers (HR = 1.64, 95% confidence interval [CI]: 1.50-1.78, P < .000001). Subgroup analysis showed that the high expression of PVT1 was closely related to the low overall survival rate of patients with clear cell renal cell carcinoma, breast cancer, cervical cancer, colon cancer, epithelial ovarian cancer, gastric cancer, lung cancer, and osteosarcoma. In addition, the high expression of PVT1 was positively correlated with tumor size (OR = 1.50, 95% CI: 1.14-1.96, P = .004), TNM stage (OR = 3.39, 95% CI: 2.73-4.20, P < .00001), lymph node metastasis (OR = 2.60, 95% CI: 1.76-3.84, P < .00001), and distant metastasis (OR = 2.94, 95% CI: 1.90-4.56, P < .00001).PVT1 could serve as a marker for the size, TNM stage, metastasis, and prognosis of different type of cancers.


Assuntos
Metástase Neoplásica/genética , Neoplasias/genética , Plasmocitoma/genética , RNA Longo não Codificante/metabolismo , Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Estadiamento de Neoplasias , Neoplasias/mortalidade , Estudos Observacionais como Assunto , Análise de Sobrevida
18.
Gene ; 712: 143961, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31279709

RESUMO

Since international federation of gynecology and obstetrics (FIGO) staging is mainly based on clinical assessment, an integrated approach for mining RNA based biomarkers for understanding the molecular deregulation of signaling pathways and RNAs in cervical cancer was proposed in this study. Publicly available data were mined for identifying significant RNAs after patient staging. Significant miRNA families were identified from mRNA-miRNA and lncRNA-miRNA interaction network analyses followed by stage specific mRNA-miRNA-lncRNA association network generation. Integrated bioinformatic analyses of selected mRNAs and lncRNAs were performed. Results suggest that HBA1, HBA2, HBB, SLC2A1, CXCL10 (stage I), PKIA (stage III) and S100A7 (stage IV) were important. miRNA family enrichment of interacting miRNA partners of selected RNAs indicated the enrichment of let-7 family. Assembly of collagen fibrils and other multimeric structures_Homosapiens_R-HSA-2022090 in pathway analysis and progesterone_CTD_00006624 in DSigDB analysis were the most significant and SLC2A1, hsa-miR-188-3p, hsa-miR-378a-3p and hsa-miR-150-5p were selected as survival markers.


Assuntos
Biomarcadores Tumorais/metabolismo , Biologia Computacional/métodos , Mineração de Dados/métodos , RNA Neoplásico/metabolismo , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/metabolismo , Colágeno/química , Metilação de DNA , Progressão da Doença , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , MicroRNAs/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Papillomaviridae/metabolismo , Infecções por Papillomavirus/complicações , Neoplasias do Colo do Útero/virologia
19.
Medicine (Baltimore) ; 98(28): e15336, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31305389

RESUMO

BACKGROUND: Human epididymis protein 4 (HE4) protein has garnered a great degree of interest as a complementary biomarker to carbohydrate antigen 125 (CA125), or even as an independent biomarker for monitoring, diagnosis, and prognostication of ovarian cancer. Its use is currently limited to ovarian cancer. Recent studies have suggested that it could also be used in other types of cancers. METHODS: The Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines was used to design this meta-analysis protocol. The final study will also be conducted under the PRISMA guidelines for systematic reviews and meta-analyses. The core bibliographic database search will be carried out by 2 reviewers working individually, with each conducting an initial screening based on titles and abstracts. The shortlisted articles will be selected for review and statistical analysis based on predefined inclusion and exclusion criteria. Study characteristics, relevant clinicopathological characteristics and statistical data required for meta-analysis (hazard ratios [HRs] and 95% confidence interval [CIs) will be extracted and compiled into a MS Excel datasheet. Meta-analysis will be performed, using a random-effects model, and the results (pooled HR and 95% CI) will be presented in the form of a forest plot. Publication bias will also be assessed by use of Egger bias indicator test and funnel plot symmetry. If data are insufficient, a narrative line of review will be pursued. DISCUSSION: HE4 protein has been shown to have great potential for clinical use as a diagnostic and prognostic marker in epithelial ovarian cancer (EOC). However, HE4 is not only limited to expression in ovarian cancer, but is also overexpressed in lung and endometrial cancers. The effectiveness of HE4 as a biomarker in cancers (other than EOC) has not yet been studied in the form of a comprehensive systematic review and meta-analysis. The results of this study should allow for expanded use of HE4 as a multiutility biomarker in multiple cancer types, thereby, elevating HE4's value as a cancer biomarker. PROSPERO REGISTRATION: CRD42019120326.


Assuntos
Carcinoma/diagnóstico , Carcinoma/metabolismo , Metanálise como Assunto , Proteínas/metabolismo , Revisão Sistemática como Assunto , Biomarcadores Tumorais/metabolismo , Humanos , Prognóstico , Projetos de Pesquisa
20.
Medicine (Baltimore) ; 98(28): e16343, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31305422

RESUMO

To estimate the BRAFV600E mutation frequency in Chinese patients with papillary thyroid carcinoma (PTC), and the diagnostic value of BRAFV600E mutation status in thyroid nodules with indeterminate TBSRTC categories.A total of 4875 consecutive samples for thyroid ultrasound-guided fine-needle aspiration cytology (FNAC) and BRAF mutation analysis were collected from patients at Jiangsu Province Hospital on Integration of Chinese and Western Medicine. Among all the cases, 314 underwent thyroidectomy. According to TBSRTC categories, FNAC was performed for a preoperative diagnosis. ROC of the subject was constructed to evaluate the diagnostic value of these 2 methods and their combination.BRAF mutation in FNAC of thyroid nodules occurred in 2796 samples (57.35%). Of 353 nodule samples from 314 patients with thyroid operation, 333 were pathologically diagnosed as PTC. Of these PTC patients, 292 (87.69%) were found to have BRAF mutation in their preoperative FNAC. In 175 cytologically indeterminate thyroid nodules, BRAF mutation identified 88% of PTC. According to ROC data, BRAF mutation testing had an obviously higher sensitivity (87.69%) and specificity (100.00%) than TBSRTC. Combining BRAF mutation testing and TBSRTC achieved the largest AUC (0.954). For 41 PTC with a negative BRAF mutation in preoperative evaluation, the repeated BRAF mutation testing found out 12 samples with BRAF mutation. The true BRAF mutation rate of Chinese PTC patients was 91.29%.Chinese patients with PTC have a higher frequency of BRAF mutation. The BRAF mutation testing affords a high diagnostic value in thyroid nodules with indeterminate cytology.


Assuntos
Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Câncer Papilífero da Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/metabolismo , Nódulo da Glândula Tireoide/patologia , Adolescente , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Biópsia por Agulha Fina , Criança , China , Análise Mutacional de DNA , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas B-raf/metabolismo , Sensibilidade e Especificidade , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/terapia , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/terapia , Tireoidectomia , Ultrassonografia de Intervenção , Adulto Jovem
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