Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 34.154
Filtrar
1.
Nat Commun ; 11(1): 4995, 2020 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-33020491

RESUMO

Endometrioid ovarian carcinoma (EnOC) demonstrates substantial clinical and molecular heterogeneity. Here, we report whole exome sequencing of 112 EnOC cases following rigorous pathological assessment. We detect a high frequency of mutation in CTNNB1 (43%), PIK3CA (43%), ARID1A (36%), PTEN (29%), KRAS (26%), TP53 (26%) and SOX8 (19%), a recurrently-mutated gene previously unreported in EnOC. POLE and mismatch repair protein-encoding genes were mutated at lower frequency (6%, 18%) with significant co-occurrence. A molecular taxonomy is constructed, identifying clinically distinct EnOC subtypes: cases with TP53 mutation demonstrate greater genomic complexity, are commonly FIGO stage III/IV at diagnosis (48%), are frequently incompletely debulked (44%) and demonstrate inferior survival; conversely, cases with CTNNB1 mutation, which is mutually exclusive with TP53 mutation, demonstrate low genomic complexity and excellent clinical outcome, and are predominantly stage I/II at diagnosis (89%) and completely resected (87%). Moreover, we identify the WNT, MAPK/RAS and PI3K pathways as good candidate targets for molecular therapeutics in EnOC.


Assuntos
Carcinoma Endometrioide/genética , Neoplasias Ovarianas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Endometrioide/metabolismo , Carcinoma Endometrioide/mortalidade , Carcinoma Endometrioide/patologia , Variações do Número de Cópias de DNA , Feminino , Humanos , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Mutação , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Prognóstico , Transdução de Sinais , Sequenciamento Completo do Exoma
2.
Medicine (Baltimore) ; 99(40): e21503, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019382

RESUMO

Hepatitis B virus (HBV) infection is a leading cause of hepatocellular carcinoma (HCC), but HBV-HCC related prognosis signature remains rarely investigated. This study was to identify an integrated long non-coding RNAs-messenger RNAs (lncRNA-mRNA) signature for prediction of overall survival (OS) and explore their underlying functions.One RNA-sequencing dataset (training set, n = 95) and one microarray dataset E-TABM-36 (validation set, n = 44) were collected. Least absolute shrinkage and selection operator analysis was performed to identify an lncRNA-mRNA prognosis signature. The OS difference of patients in the high-risk and low-risk risk groups was evaluated by Kaplan-Meier curve. Area under the receiver operating characteristic curve (AUC), Harrell concordance index (C-index) calculation, and multivariate analyses with clinical characteristics were used to determine the prognostic ability. Furthermore, a coexpression network was constructed to interpret the functions.Nine signature genes (3 lncRNAs and 6 mRNAs) were selected to generate the risk score model. Patients belonging to the high-risk group showed a significantly shorter survival than those of the low-risk group. The prediction accuracy of the risk score for 5-year OS was 0.936 and 0.905 for the training set and validation set, respectively. Also, this risk score was independent of various clinical variables for the prognosis prediction. Incorporation of the risk score remarkably increased the predictive power of the routine clinical prognostic factors (vascular invasion status, tumor recurrence status) (AUC = 0.942 vs 0.628; C-index = 0.7997 vs 0.6908). Furthermore, LncRNA insulin-like growth factor 2 antisense RNA (IGF2-AS) and long intergenic non-protein coding RNA 342 (LINC00342) were predicted to exert tumor suppression effects by regulating homeobox D1 (HOXD1) and secreted frizzled related protein 5 (SFRP5), respectively; while lncRNA rhophilin Rho GTPase binding protein 1 antisense RNA 1 (RHPN1-AS1) may possess carcinogenic potential by promoting the transcription of chromobox 2 (CBX2), cell division cycle 20 (CDC20), matrix metallopeptidase 12 (MMP12), stratifin (SFN), tripartite motif containing 16 (TRIM16), and uroplakin 3A (UPK3A). These mRNAs may be associated with cell proliferation or apoptosis related pathways.This study may provide a novel, effective prognostic biomarker, and some therapeutic targets for HBV-HCC patients.


Assuntos
Carcinoma Hepatocelular/genética , Hepatite B/genética , Neoplasias Hepáticas/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Idoso , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/virologia , Estudos de Casos e Controles , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Medição de Risco
3.
Medicine (Baltimore) ; 99(40): e22203, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019395

RESUMO

Breast cancer (BC) is a disease of high mortality rate because of high malignant, while early diagnosis and personal management may make a better prognosis possible. This study aimed to establish and validate lncRNAs signatures to improve the prognostic prediction for BC.RNA sequencing data along with the corresponding clinical information of patients with BC were gained from The Cancer Genome Atlas (TCGA). Prognostic differentially expressed lncRNAs were obtained using differentially expressed lncRNAs analysis (P value <.01 and |fold change| > 2) and univariate cox regression (P value <.05). By applying least absolute shrinkage and selection operation (LASSO) Cox regression analysis along with 10-fold cross-validation, 2 lncRNA-based signatures were constructed in the training, test and whole set.A 14-lncRNAs signature and a 10-lncRNAs signature were built for overall survival (OS) and relapse-free survival (RFS) respectively in the 3 sets. BC patients were divided into high-risk groups and low-risk groups depended on median risk score value. Significant differences were found for OS and RFS between 2 groups in the 3 sets. The time-dependent receiver operating characteristic (ROC) curves analysis demonstrated that our lncRNAs signatures had better predictive capacities of survival and recurrence for BC patients as well as enhancing the predictive ability of the tumor node metastasis (TNM) stage system.These results indicate that the 2 lncRNAs signatures with the potential to be biomarkers to predict the prognosis of BC for OS and RFS.


Assuntos
Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , RNA Longo não Codificante/genética , Adulto , Idoso , Biomarcadores Tumorais/genética , Neoplasias da Mama/mortalidade , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Curva ROC
4.
Medicine (Baltimore) ; 99(35): e21895, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871920

RESUMO

MicroRNAs (miRNAs) refers to a small, short non-coding RNA of endogenous class. They have shown to have an increasingly altered expression in many types of cancer, including colorectal cancer (CRC).In the present study, miRNA TaqManMGB and qRT-PCR was used to quantify the expression and clinical significance of 3 mature human miRNA in 82 pairs of colorectal adenocarcinoma tissues and normal adjacent tissue samples (NATS) collected from patients of the south-east part of Romania. Differences between CRC and NATS were analyzed using Wilcoxon test, while correlations between miRNAs expression levels and clinicopathological features were examined using non-parametric tests. In addition, the ability of selected miRNAs to function as biomarkers and, as potential indicators in CRC prognosis was also examined.When the miRNA expression was compared in CRC related NATS, miR-143, and miR-145 were significantly underexpressed (4.99 ±â€Š-1.02 vs -5.66 ±â€Š-1.66, P < .001; -4.85 ±â€Š-0.59 vs -9.27 ±â€Š-1.51, P < .001, respectively), while the pattern of miR-92a was significantly overexpressed (-5.55 ±â€Š-2.83 vs -4.92 ±â€Š-2.44, P < .001). Moreover, the expression levels of selected miRNAs were identified to be correlated with gradual increases in fold change expression with the depth of tumor invasion, lymph node invasion, and maximal increases with distant metastasis. Furthermore, the receiver operating characteristic analysis demonstrated that potential diagnostic of miR-143, miR-145, and miR-92a in discriminating CRC from NATS, with the area under the curve of 0.74, 0.85, and 0.84 respectively. The Kaplan-Meier and the log-rank test showed that a high level of miR-92a and low levels of miR-143 and miR-145 predicted poor survival rate in our cohorts.In conclusion, we can summarize that miR-145 and miR-143 are decreased, while miR-92 is increased in CRC compared to NATS, and associated with different stages of CRC pathogenesis. Thus, the expression of selected miRNAs can represent potential diagnostic and prognostic tools in patients with CRC from Romania.


Assuntos
Adenocarcinoma/diagnóstico , Biomarcadores Tumorais/genética , Neoplasias Colorretais/diagnóstico , MicroRNAs/genética , Adenocarcinoma/genética , Adenocarcinoma/patologia , Idoso , Área Sob a Curva , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Romênia , Transcriptoma
5.
Medicine (Baltimore) ; 99(33): e21483, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32871993

RESUMO

BACKGROUD: More and more studies are investigating the influence of the expression of MicroRNA-21 (miRNA-21) on prognosis and clinical significance in patients with lung cancer, but the results are contradictory and uncertain. A meta-analysis was conducted with controversial data to accurately assess the issue. METHODS: A detailed search of relevant research in Wanfang, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure (CNKI), the Chongqing VIP Chinese Science and Technology Periodical Database, PubMed, Embase, Web of Science and other databases. Two reviewers independently conducted data extraction and literature quality evaluation. Odd ratio and its 95% confidence intervals were used to evaluate the relationship between miRNA-21 and clinicopathological characteristics of lung cancer patients. Hazard ratios and its 95% confidence intervals To assess the prognostic effect of miRNA-21 on overall survival and disease-free survival. Meta analysis was performed using RevMan 5.3 and Stata 14.0 software. RESULTS: This study will provide a high-quality evidence-based medical evidence of the correlations between miRNA-21 expression and overall survival, disease-free survival and clinicopathological features. CONCLUSION: The study will provide updated evidence to evaluate whether the expression of miRNA-21 is in association with poor prognosis in patients with lung cancer. ETHICS AND DISSEMINATION: The private information from individuals will not publish. This systematic review also will not involve endangering participant rights. Ethical approval is not available. The results may be published in a peer- reviewed journal or disseminated in relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/X3MD6.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Pulmonares/genética , MicroRNAs , Projetos de Pesquisa , Humanos , Metanálise como Assunto , Prognóstico , Revisões Sistemáticas como Assunto
6.
Anticancer Res ; 40(10): 5411-5416, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988861

RESUMO

BACKGROUND: Patients with inflammatory bowel disease have markedly increased risk for developing colitis-associated colorectal adenocarcinoma (CAC). There is no established prognostic biomarker for CAC. MATERIALS AND METHODS: A retrospective study was performed on a cohort of 57 CACs. Expression of caudal type homeobox transcription factor 2 (CDX2) and YES-associated protein 1 (YAP1) expression was correlated with clinicodemographic and histopathological features. RESULTS: Neither YAP1 nor CDX2 expression alone was significantly associated with tumor invasion beyond the muscularis propria or lymph node status. However, a subgroup of CAC with double negativity for expression of YAP1 and CDX2 was more frequently found in younger patients, and more frequently associated with higher pathological tumor stage and nodal metastasis. Furthermore, a positive correlation between CDX2 and YAP1 expression was identified in CAC and sporadic colorectal adenocarcinoma. CONCLUSION: Our study demonstrates that double negativity for expression of YAP1 and CDX2 defines a subgroup of CAC with early onset and aggressive clinical features.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Fator de Transcrição CDX2/genética , Colite/genética , Neoplasias Colorretais/genética , Fatores de Transcrição/genética , Adenocarcinoma/complicações , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adulto , Biomarcadores Tumorais/genética , Colite/complicações , Colite/patologia , Neoplasias Colorretais/complicações , Neoplasias Colorretais/patologia , Feminino , Humanos , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico
7.
Nat Commun ; 11(1): 4660, 2020 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-32938908

RESUMO

Intratumor spatial heterogeneity facilitates therapeutic resistance in glioblastoma (GBM). Nonetheless, understanding of GBM heterogeneity is largely limited to the surgically resectable tumor core lesion while the seeds for recurrence reside in the unresectable tumor edge. In this study, stratification of GBM to core and edge demonstrates clinically relevant surgical sequelae. We establish regionally derived models of GBM edge and core that retain their spatial identity in a cell autonomous manner. Upon xenotransplantation, edge-derived cells show a higher capacity for infiltrative growth, while core cells demonstrate core lesions with greater therapy resistance. Investigation of intercellular signaling between these two tumor populations uncovers the paracrine crosstalk from tumor core that promotes malignancy and therapy resistance of edge cells. These phenotypic alterations are initiated by HDAC1 in GBM core cells which subsequently affect edge cells by secreting the soluble form of CD109 protein. Our data reveal the role of intracellular communication between regionally different populations of GBM cells in tumor recurrence.


Assuntos
Antígenos CD/metabolismo , Neoplasias Encefálicas/patologia , Glioblastoma/patologia , Histona Desacetilase 1/metabolismo , Proteínas de Neoplasias/metabolismo , Animais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/mortalidade , Feminino , Proteínas Ligadas por GPI/metabolismo , Regulação Neoplásica da Expressão Gênica , Glioblastoma/genética , Glioblastoma/metabolismo , Glioblastoma/mortalidade , Histona Desacetilase 1/antagonistas & inibidores , Histona Desacetilase 1/genética , Histona Desacetilase 2/genética , Histona Desacetilase 2/metabolismo , Humanos , Camundongos SCID , Fenilbutiratos/farmacologia , Transdução de Sinais , Microambiente Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Zhonghua Bing Li Xue Za Zhi ; 49(10): 1036-1040, 2020 Oct 08.
Artigo em Chinês | MEDLINE | ID: mdl-32992419

RESUMO

Objective: To investigate the expression status and diagnostic value of SRY related high mobility group box 11 (SOX-11) and transcription factor E-3 (TFE3) in solid pseudopapillary tumors of pancreas (SPTPs). Methods: Thirty-eight cases of SPTPs, 36 cases of well-differentiated pancreatic neuroendocrine tumors (PanNETs) and six cases of pancreatic acinar cell carcinomas (PACCs) were collected at the Affiliated Drum Tower Hospital of Nanjing University Medical School from 2012 to 2019. The expression of SOX-11, TFE3 and ß-catenin was detected by immunohistochemistry, and the TFE3 gene status was detected by FISH in 18 cases of SPTPs. Results: Among the 38 SPTP patients, 29 were female and 9 were male, with a mean age of 50 years; among 36 PanNET patients, 32 were female and 4 were male, with a mean age of 39 years; for the six PACC patients, four were male and two were female, with a mean age of 60 years. ß-catenin was positive in all 38 SPTPs, but was negative in all 36 PanNETs and 5/6 PACCs. SOX-11 was positive in 35/38 (92.1%) of SPTPs, but was negative in all 36 PanNETs and 6 PACCs. TFE3 was positive in 36/38 (94.7%) of SPTPs, but was negative in all 36 PanNETs and 6 PACCs. Among these three tumors, the specificity and sensitivity of ß-catenin were 97.6% and 100.0%, the specificity and sensitivity of SOX-11 were 92.1% and 100.0%, the specificity and sensitivity of TFE3 were 94.7% and 100.0%, respectively. There was a significant difference of the expression status of all three markers in SPTPs compared with PanNETs and PACCs (P<0.01). The results of SOX-11 and TFE3 immunostaining showed high consistency (Kappa>0.6). No gene rearrangement (0/18) of TFE3 was found in SPTPs. Conclusion: SOX-11 and TFE3 are highly expressed in SPTPs, and their specificity in the differential diagnosis of SPTPs is better than that of ß-catenin.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Acinares , Adulto , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Pâncreas , Fatores de Transcrição SOXC/metabolismo
9.
Anticancer Res ; 40(10): 5925-5932, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988924

RESUMO

BACKGROUND/AIM: Paired box 8 (PAX8) is an organ-specific marker discriminating Müllerian and breast carcinomas. Recent studies have described PAX8 expression in a small subset of breast carcinomas, which may cause a diagnostic pitfall in the determination of cancer origin. The aim of this study was to investigate characteristics of PAX8-expressing metastatic breast carcinomas (MBCs) to help elucidate the primary site of occurrence. PATIENTS AND METHODS: Using immunohistochemistry, we examined PAX8 status in 80 MBCs and 52 matched primary breast carcinomas (PBCs). RESULTS: A total of 20% of MBCs displayed PAX8 expression and the concordance rate of PAX8 expression between MBCs and PBCs was 92.3%. In MBCs, PAX8 expression was significantly associated with high-grade features (p=0.042), estrogen and progesterone receptor negativities (p=0.005 and p=0.017, respectively). CONCLUSION: PAX8 may be identified in MBCs with high-grade and non-luminal molecular subtypes. Careful assessment is needed when designating a primary site relying principally on PAX8 positivity.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Imuno-Histoquímica , Fator de Transcrição PAX8/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Pessoa de Meia-Idade
10.
Medicine (Baltimore) ; 99(38): e22261, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957376

RESUMO

Pancreatic cancer (PC) is one of the major causes of cancer mortality in developed countries. Therefore, there is an urgent need to derive biomarkers for early diagnosis of PC patients at high risk.This study was designed to identify a panel of miRNAs that might serve as biomarkers for the early diagnosis of PC.The data containing both PC and control samples were extracted from the Gene Expression Omnibus (GEO) database. EdgeR was applied to identify the differentially expressed miRNAs and genes between PC patients and healthy controls. Then a miRNA-mRNA network was constructed based on the differentially expressed miRNAs and genes. The miRNAs-based biomarker for PC was finally constructed by random forest. Finally, AUC was used to evaluate the performance of miRNAs to classify PC and control samples.A total of 33 differentially expressed miRNAs, 753 differentially expressed genes, and 8 miRNAs (hsa-mir-139, hsa-mir-31, hsa-mir-196b, hsa-mir-221, hsa-mir-203b, hsa-mir-215, hsa-mir-144, and hsa-mir-4433b) that play important roles in PC were identified. The target genes of these miRNAs were found to be mainly enriched in negative regulation of acute inflammatory response cell-substrate responses, and o-glycan processing pathways. The constructed biomarkers based on these 8 miRNAs could distinguish samples coming from PC and healthy controls.We identified a panel of eight-miRNAs that would serve as early diagnostic biomarkers for PC patients.


Assuntos
Biomarcadores Tumorais/genética , Detecção Precoce de Câncer , MicroRNAs/genética , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Perfilação da Expressão Gênica , Humanos , Prognóstico , RNA Mensageiro/genética
11.
Anticancer Res ; 40(10): 5509-5516, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988874

RESUMO

BACKGROUND/AIM: Extracellular vesicles (EVs) can mediate drug resistance within the tumor microenvironment by delivering bioactive molecules, including proteins. Here, we performed a comparative proteomic analysis of EVs secreted by A549 lung cancer cells and their cisplatin-resistant counterparts in order to identify proteins involved in drug resistance. MATERIALS AND METHODS: Cells were co-cultivated using a transwell system to evaluate EV exchange. EVs were isolated by ultracentrifugation and analyzed using microscopy and nanoparticle tracking. EV proteome was analyzed by mass spectrometry. RESULTS: EV-mediated communication was observed between co-cultured A549 and A549/CDDP cells. EVs isolated from both cells were mainly exosome-like structures. Extracellular matrix components, cell adhesion proteins, complement factors, histones, proteasome subunits and membrane transporters were found enriched in the EVs released by cisplatin-resistant cells. CONCLUSION: Proteins identified in this work may have a relevant role in modulating the chemosensitivity of the recipient cells and could represent useful biomarkers to monitor cisplatin response in lung cancer.


Assuntos
Biomarcadores Tumorais/genética , Cisplatino/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Proteoma/genética , Células A549 , Cisplatino/efeitos adversos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Exossomos/efeitos dos fármacos , Exossomos/genética , Vesículas Extracelulares/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Espectrometria de Massas , Proteômica/métodos , Microambiente Tumoral/efeitos dos fármacos
12.
Anticancer Res ; 40(10): 5557-5566, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988879

RESUMO

BACKGROUND/AIM: E- and P-cadherin (E-cadh, P-cadh) control tumor cell invasion, metastatic or stemness potential and chemotherapy resistance. The study aimed to assess E- and P-cadherin expression in breast cancer molecular subtypes. MATERIALS AND METHODS: Immunohistochemistry for E-cadh and P-cadh was performed for 97 breast cancer cases. Membrane (M), cytoplasmic (C) or mixed (MC) patterns of E-cadh and P-cadh were considered in our evaluation. RESULTS: E-cadh and P-cadh C pattern was significantly correlated in the HER2 subtype (p=0.031). P-cadh M pattern was highly specific for the HER2 subtype (p=0.002). Only P-cadh C characterized the triple negative breast cancer subtype (p=0.015). For Luminal B/HER2 cases, P-cadh M pattern was strongly coexpressed with the E-cadh MC pattern (p=0.012). Progesterone receptor (PR) expression influenced E-cadh M pattern in the Luminal B/HER2 subtype (p=0.042). CONCLUSION: E- and P-cadherins define distinct subgroups within breast cancer molecular subtypes. Our findings support the inclusion of E- and P-cadherin into breast cancer molecular classification.


Assuntos
Antígenos CD/genética , Biomarcadores Tumorais/genética , Caderinas/genética , Neoplasias de Mama Triplo Negativas/genética , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Células-Tronco Neoplásicas/metabolismo , Receptor ErbB-2/genética , Receptores Estrogênicos/genética , Receptores de Progesterona/genética , Neoplasias de Mama Triplo Negativas/classificação , Neoplasias de Mama Triplo Negativas/patologia
13.
Anticancer Res ; 40(10): 5567-5575, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988880

RESUMO

BACKGROUND/AIM: Stage-specific embryonic antigen-4 (SSEA-4) expression is associated with malignant aggressiveness and is useful as a marker for identifying cancer stem cells. Our aim was to assess the relationship between hormonal therapy and SSEA-4 expression in prostate cancer (PC). MATERIALS AND METHODS: SSEA-4 expression in paired specimens from PC patients who underwent neoadjuvant hormonal therapy (NHT) and radical prostatectomy (60 pre-NHT specimens and 60 post-NHT specimens) was evaluated using immunohistochemistry. Proliferation index (PI) and apoptotic index (AI) were also evaluated. RESULTS: Post-NHT tissues had significantly elevated SSEA-4 expression whereas anti-tumor effects of NHT were inversely correlated with SSEA-4 expression level. SSEA-4 expression in post-NHT tissues was significantly associated with biochemical recurrence-free survival. SSEA-4 expression in the post-NHT tissues was positively associated with PI and negatively done with AI. CONCLUSION: SSEA-4 is a potential therapeutic target for limiting the malignant potential in hormone-naïve PC when considering the use of NHT.


Assuntos
Antineoplásicos Hormonais/administração & dosagem , Biomarcadores Tumorais/genética , Neoplasias da Próstata/tratamento farmacológico , Antígenos Embrionários Estágio-Específicos/genética , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Próstata/patologia , Prostatectomia , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia
14.
Anticancer Res ; 40(10): 5593-5600, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988883

RESUMO

BACKGROUND: Despite improved treatment for gastric cancer (GC), the prognosis of advanced disease remains poor. Further investigation of the oncogenic sequence for GC is needed. MATERIALS AND METHODS: The expression of TYRO3 protein tyrosine kinase in five GC cell lines was confirmed using western blotting. TYRO3 knockdown in GC cells, and bromodeoxyuridine and Transwell assays were used to examine the functions of TYRO3 in tumor proliferation and invasion. Finally, TYRO3 expression in 138 patients who underwent curative gastric resection for advanced GC (Union for International Cancer Control stage II/III) was tested by immunohistochemistry, and the association between prognosis and TYRO3 expression was analyzed. RESULTS: TYRO3 was detected at various levels in all the tested GC cell lines. Deleting TYRO3 significantly suppressed proliferation and invasion. Immunohistochemistry revealed TYRO3 expression was an independent prognostic factor for overall survival in patients with GC. CONCLUSION: TYRO3 appears to mediate tumor progression and predict prognosis of patients with GC.


Assuntos
Biomarcadores Tumorais/genética , Prognóstico , Receptores Proteína Tirosina Quinases/genética , Neoplasias Gástricas/genética , Idoso , Carcinogênese/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Proteínas Proto-Oncogênicas c-akt/genética , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia
15.
Anticancer Res ; 40(10): 5601-5609, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988884

RESUMO

BACKGROUND/AIM: Since pathways involving LRRC17 are related to the survival of patients with various cancers, we analyzed LRRC17 as a prognostic gene in serous ovarian cancer. MATERIALS AND METHODS: Data were collected from Gene Expression Omnibus (GSE9891, GSE13876, and GSE26712) and The Cancer Genome Atlas (TCGA). We performed survival analyses using C statistics, area under the curve, survival plot with optimal cutoff level, and cox proportional regression. Zebrafish embryos were used as an in vivo model. RESULTS: The prognosis of patients with high LRRC17 expression was poorer than that of patients with low LRRC17 expression. Multivariate regression analysis showed that LRRC17 expression, age, and stage were independently related with survival. Knockdown of lrrc17 reduced survival rate and delayed development in zebrafish embryos. We also found that lrrc17 is important for cell viability by protecting from p53-dependent apoptosis. CONCLUSION: LRRC17 could be a prognostic gene in ovarian cancer as it regulates cancer cell viability through the p53 pathway.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Ovarianas/genética , Proteínas/genética , Proteína Supressora de Tumor p53/genética , Idoso , Apoptose/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Técnicas de Silenciamento de Genes , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Prognóstico
16.
Anticancer Res ; 40(10): 5659-5666, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988890

RESUMO

BACKGROUND/AIM: Long interspersed nuclear element-1 (LINE-1) methylation status is a marker for global DNA methylation. However, the relationship between LINE-1 methylation and the biology of lung adenocarcinoma remains unclear. Here, we aimed to examine the role of LINE-1 in lung cancer. MATERIALS AND METHODS: LINE-1 methylation levels were quantified by bisulfite pyrosequencing of resected tumor specimens from 162 patients with lung adenocarcinoma. The relationships of LINE-1 methylation with clinicopathological factors, gene mutations, and Ki-67 immunoreactivity were investigated. RESULTS: LINE-1 hypomethylation was associated with tumor invasion and advanced stage. TP53 mutations were more frequently detected in the LINE-1 hypomethylation group than in the hypermethylation group. LINE-1 hypomethylation was associated with poor recurrence-free survival, high maximum standardized uptake value in positron-emission tomography, and high Ki-67 expression in tumors. CONCLUSION: LINE-1 hypomethylation was associated with high-grade malignancy and poor prognosis in lung adenocarcinoma, but was not related to driver mutations.


Assuntos
Adenocarcinoma de Pulmão/genética , Biomarcadores Tumorais/genética , Metilação de DNA/genética , Elementos Nucleotídeos Longos e Dispersos/genética , Adenocarcinoma de Pulmão/patologia , Adulto , Idoso , Núcleo Celular/genética , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Antígeno Ki-67/genética , Masculino , Pessoa de Meia-Idade , Mutação/genética , Prognóstico , Proteína Supressora de Tumor p53/genética
17.
Anticancer Res ; 40(10): 5815-5821, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988910

RESUMO

BACKGROUND/AIM: Glioma-associated oncogene 1 (GLI1) is an important transcription factor in the hedgehog signalling pathway and tumour formation. We evaluated the clinical significance of GLI1 expression as a prognostic factor in patients with locally advanced gastric cancer (GC). PATIENTS AND METHODS: GLI1 expression levels were measured by quantitative real-time polymerase chain reaction analysis of cancerous and adjacent normal mucosa specimens obtained from 142 patients with Stage II/III GC administered adjuvant chemotherapy with S-1 after curative resection. The associations of GLI1 expression with clinicopathological features and survival were evaluated. RESULTS: Clinicopathological features and GLI1 expression showed no association. Overall survival was significantly poorer in the high compared to the low GLI1 expression group (p=0.04). Multivariate analysis revealed that GLI1 expression was a significant independent prognostic factor [p=0.019, hazard ratio (HR)=1.94, 95% confidence interval (CI)=1.70-3.38]. CONCLUSION: GLI1 expression may be a useful prognostic marker in patients with locally advanced GC.


Assuntos
Biomarcadores Tumorais/genética , Prognóstico , Neoplasias Gástricas/tratamento farmacológico , Proteína GLI1 em Dedos de Zinco/genética , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Combinação de Medicamentos , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , Estadiamento de Neoplasias , Ácido Oxônico/administração & dosagem , Ácido Oxônico/efeitos adversos , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Tegafur/administração & dosagem , Tegafur/efeitos adversos
18.
Anticancer Res ; 40(10): 5883-5893, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988919

RESUMO

BACKGROUND/AIM: Somatic mutations were investigated in 21 patients with postmenopausal estrogen receptor (ER)-positive and human epidermal growth factor receptor-2 (HER-2)-positive (ER+HER2+) breast cancer (BC) treated with neoadjuvant letrozole and lapatinib, to identify their distinct molecular landscape. PATIENTS AND METHODS: We used tissue samples of 21 patients from phase II Neo ALL-IN cohort, and somatic alterations were examined using targeted exome sequencing performed in Foundation Medicine, Inc. (FMI). RESULTS: TP53 (61.9%) and PIK3CA (57.1%) were the two most frequently mutated genes that were inter-correlated (p=0.026). They were associated with unfavorable clinical outcomes, particularly when accompanying PIK3CA mutations at exon 9 in helical domains. Meanwhile, MLL2 alteration was negatively associated with mutations of TP53 or PIK3CA, and it tended to be present in patients with low KI-67 levels and no initial nodal involvement. Moreover, patients with MLL2 mutations numerically showed more favorable overall response rates (ORR) (80% vs. 56.2%) and better 5-year event-free survival (EFS) rates (100% vs. 87.5%) compared to the wild-type. CONCLUSION: Mutations in TP53 and PIK3CA hotspot at exon 9 may be potential negative predictors of ER+HER2+ BC treated with neoadjuvant letrozole and lapatinib, while MLL2 inactivating mutation might confer therapeutic benefit in these patients.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Classe I de Fosfatidilinositol 3-Quinases/genética , Proteínas de Ligação a DNA/genética , Proteínas de Neoplasias/genética , Proteína Supressora de Tumor p53/genética , Idoso , Biomarcadores Tumorais/genética , Mama/efeitos dos fármacos , Mama/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Receptor alfa de Estrogênio/genética , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Lapatinib/administração & dosagem , Letrozol/administração & dosagem , Pessoa de Meia-Idade , Mutação/genética , Intervalo Livre de Progressão , Receptor ErbB-2/genética
19.
Anticancer Res ; 40(10): 5777-5785, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988905

RESUMO

BACKGROUND/AIM: Emerging evidence suggests that Insulin-like growth factor II mRNA-binding protein 3 (IMP3) promotes tumor progression in several human malignancies. We investigated whether IMP3 expression has clinicopathological and prognostic significance in gallbladder adenocarcinoma (GBAC). PATIENTS AND METHODS: We examined immunohistochemical IMP3 expression in 204 GBACs and its associations with clinicopathological parameters and patient outcomes. RESULTS: The majority (87.7%) of GBACs exhibited at least focal cytoplasmic and membranous IMP3 immunoreactivity. Tumor-specific IMP3 expression highlighted proper muscle invasion, which was not detected in the corresponding hematoxylin and eosin-stained slides. This finding upgraded pathological tumor stage (pT) from pT1a to pT1b in four well-differentiated GBACs. High IMP3 expression was associated with high histological grade, advanced stage, and lymphatic invasion, as well as worse overall survival. CONCLUSION: Tumor-specific IMP3 expression in GBAC is helpful in determining the tumor extent, especially in well-differentiated tumors. High IMP3 expression reflects aggressive oncogenic behavior of GBAC. IMP3 expression may be used as a diagnostic and prognostic marker in GBAC.


Assuntos
Carcinoma/genética , Neoplasias da Vesícula Biliar/genética , Prognóstico , Proteínas de Ligação a RNA , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Carcinoma/patologia , Feminino , Neoplasias da Vesícula Biliar/patologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , Proteínas de Ligação a RNA/genética
20.
Nat Commun ; 11(1): 4861, 2020 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-32978398

RESUMO

Advanced tumours are often heterogeneous, consisting of subclones with various genetic alterations and functional roles. The precise molecular features that characterize the contributions of multiscale intratumour heterogeneity to malignant progression, metastasis, and poor survival are largely unknown. Here, we address these challenges in breast cancer by defining the landscape of heterogeneous tumour subclones and their biological functions using radiogenomic signatures. Molecular heterogeneity is identified by a fully unsupervised deconvolution of gene expression data. Relative prevalence of two subclones associated with cell cycle and primary immunodeficiency pathways identifies patients with significantly different survival outcomes. Radiogenomic signatures of imaging scale heterogeneity are extracted and used to classify patients into groups with distinct subclone compositions. Prognostic value is confirmed by survival analysis accounting for clinical variables. These findings provide insight into how a radiogenomic analysis can identify the biological activities of specific subclones that predict prognosis in a noninvasive and clinically relevant manner.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/genética , Perfilação da Expressão Gênica/métodos , Heterogeneidade Genética , Biomarcadores Tumorais/genética , Mama , Ciclo Celular/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Genômica , Humanos , Imageamento Tridimensional/métodos , Análise Multivariada , Prognóstico , Análise de Sobrevida , Transcriptoma
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA