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1.
J Cancer Res Ther ; 16(4): 800-803, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32930121

RESUMO

Aims: Some studies investigated the association between nestin and the overall survival (OS) of nonsmall cell lung cancer (NSCLC). However, the results were conflicted and inconclusive. Therefore, we performed this meta-analysis to determine the association between nestin and OS of NSCLC. Materials and Methods: PubMed and EMBASE were searched to find relevant studies. The strength of the association was calculated with the hazard ratios (HRs) and respective 95% confidence intervals (CIs). Results: High expression of nestin was significantly associated with OS of NSCLC (HR = 2.09; 95% CI = 1.59-2.77). In the stratified analysis by race, we found that the expression of nestin was significantly associated with OS of NSCLC in Asians (HR = 3.02; 95% CI = 1.80-5.07) and Caucasians (HR = 1.81; 95% CI = 1.21-2.71). In addition, when we limited the meta-analysis to studies that controlled for clinical parameters, a significant association between nestin and OS of NSCLC remained (HR = 2.19; 95% CI = 1.54-3.11). A sensitivity analysis showed no substantial modification of the estimates after exclusion of individual studies. Conclusions: In conclusion, this meta-analysis suggested that high expression of nestin was significantly associated with OS of NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Nestina/biossíntese , Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Humanos , Neoplasias Pulmonares/patologia , Prognóstico , Taxa de Sobrevida
2.
Cancer Treat Rev ; 88: 102064, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32622272

RESUMO

The overexpression of human epidermal growth factor receptor-2 (HER2) results in a biologically and clinically aggressive breast cancer (BC) subtype. Since the introduction of anti-HER2 targeted agents, survival rates of patients with HER2-positive metastatic BC have dramatically improved. Currently, although the treatment decision process in metastatic BC is primarily based on HER2 and hormone-receptor (HR) status, a rapidly growing body of data suggests that several other sources of biological heterogeneity may characterize HER2-positive metastatic BC. Moreover, pivotal clinical trials of new anti-HER2 antibody-drug conjugates showed encouraging results in HER2-low metastatic BC, thus leading to the possibility, in the near future, to expand the pool of patients suitable for HER2-targeted treatments. The present review summarizes and puts in perspective available evidence on biomarkers that hold the greatest promise to become potentially useful tools for optimizing HER2-positive metastatic BC patients' prognostic stratification and treatment in the next future. These biomarkers include HER2 levels and heterogeneity, HER3, intrinsic molecular subtypes by PAM50 analysis, DNA mutations, and immune-related factors. Molecular discordance between primary and metastatic tumors is also discussed.


Assuntos
Neoplasias da Mama/metabolismo , Receptor ErbB-2/metabolismo , Receptores de Superfície Celular/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/enzimologia , Neoplasias da Mama/genética , Feminino , Humanos , Metástase Neoplásica , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptor ErbB-2/biossíntese , Receptor ErbB-2/genética , Receptor ErbB-3/biossíntese , Receptor ErbB-3/genética , Receptor ErbB-3/metabolismo
3.
Anticancer Res ; 40(7): 3801-3809, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620619

RESUMO

AIM: Cancer stem-like cell (CSC) markers and the role of CSCs derived from papillary thyroid carcinoma (PTC) in pathogenesis are unclear. This study aimed to investigate CSC properties using tumor spheres from passaged PTC cells but without sorting CSCs. MATERIALS AND METHODS: To identify the properties of CSCs derived from PTC, the expression of SRY-box transcription factor 2(SOX2), octamer-binding transcription factor 4 (OCT4), Nanog homeobox (NANOG), thyroglobulin (TG), thyroid-stimulating hormone receptor (TSHR), E-cadherin, YES-associated protein 1 (YAP1), and signal transducer and activator of transcription 3 (STAT3) was investigated in tumor spheres serially passaged without sorting CSCs. RESULTS: The cultured tumor spheres had cancer stemness; high expression of OCT4, SOX2, NANOG, and YAP1; low expression of E-cadherin; and varied expression of TG, TSHR, and STAT3. PTC tumor spheres transfected with small interfering RNA targeting YAP1 had fewer CSC properties than the non-transfected tumor spheres did. CONCLUSION: Tumor spheres derived from PTC cells by passaging without sorting CSCs have more stem-like cell properties, and less differentiation potential. Thus, this simple and cost-effective method can be used for the enrichment of PTC stemness for employment in cell-based models, reducing the need for use of animal models.


Assuntos
Células-Tronco Neoplásicas/patologia , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Proteínas Adaptadoras de Transdução de Sinal/biossíntese , Proteínas Adaptadoras de Transdução de Sinal/genética , Antígenos CD/biossíntese , Antígenos CD/genética , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Caderinas/biossíntese , Caderinas/genética , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Humanos , Células-Tronco Neoplásicas/metabolismo , Fator 3 de Transcrição de Octâmero/biossíntese , Fator 3 de Transcrição de Octâmero/genética , Fator de Transcrição STAT3/biossíntese , Fator de Transcrição STAT3/genética , Esferoides Celulares , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/metabolismo , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismo , Fatores de Transcrição/biossíntese , Fatores de Transcrição/genética
4.
Medicine (Baltimore) ; 99(28): e21158, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664150

RESUMO

Prostate cancer (PCa) is a highly aggressive malignant tumor and the biological mechanisms underlying its progression remain unclear.We performed weighted gene co-expression network analysis in PCa dataset from the Cancer Genome Atlas database to identify the key module and key genes related to the progression of PCa. Furthermore, another independent datasets were used to validate our findings.A total of 744 differentially expressed genes were screened out and 5 modules were identified for PCa samples from the Cancer Genome Atlas database. We found the brown module was the key module and related to tumor grade (R2 = 0.52) and tumor invasion depth (R2 = 0.39). Besides, 24 candidate hub genes were screened out and 2 genes (BIRC5 and DEPDC1B) were identified and validated as real hub genes that associated with the progression and prognosis of PCa. Moreover, the biological roles of BIRC5 were related to G-protein coupled receptor signal pathway, and the functions of DEPDC1B were related to the G-protein coupled receptor signal pathway and retinol metabolism in PCa.Taken together, we identified 1 module, 24 candidate hub genes and 2 real hub genes, which were prominently associated with PCa progression. With more experiments and clinical trials, these genes may provide a promising future for PCa treatment.


Assuntos
Biomarcadores Tumorais/genética , Biologia Computacional/métodos , Regulação Neoplásica da Expressão Gênica , Neoplasias da Próstata/metabolismo , Biomarcadores Tumorais/biossíntese , Progressão da Doença , Perfilação da Expressão Gênica , Humanos , Masculino , Gradação de Tumores , Prognóstico , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Transcriptoma/genética
5.
J Cancer Res Clin Oncol ; 146(10): 2447-2460, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32627077

RESUMO

BACKGROUND: Despite great advances in its early diagnosis and treatment, lung cancer is still an intractable disease and the second leading cause of cancer-related deaths and morbidity in the world. The family of Polo-like kinases (PLKs) consists of five serine/threonine kinases, which have been reported to participate in various human diseases. However, the expression and prognostic value of each PLK in human lung cancer have not been fully understood. This study analyzed mRNA expression and prognostic value of different PLKs in human non-small cell lung cancer (NSCLC). METHODS: First, mRNA expression of PLKs in patients with NSCLC from the Oncomine and the Gene Expression Profiling Interactive Analysis (GEPIA) database was investigated. Then, a Kaplan-Meier plotter was employed for survival analysis. The sequence alteration for PLKs was analyzed using The Cancer Genome Atlas (TCGA) and the cBioPortal database. Additionally, we analyzed the association among different PLKs using the LinkedOmics database. Finally, the enrichment analysis of PLKs was achieved using the DAVID database. RESULTS: The mRNA expression levels of PLK1 and PLK4 were significantly overexpressed, while mRNA expression level of PLK3 was underexpressed in patients with NSCLC. mRNA expressions of PLK1 and PLK4 were significantly and positively related to the tumor stage of NSCLC. Increased expressions of PLK1, PLK4, and PLK5 and decreased expression of PLK2 were attributed to limited overall survival time in NSCLC. PLK1 was positively correlated with PLK4 via the LinkedOmics database. CONCLUSIONS: PLKs are relevant targets for NSCLC treatment, especially PLK1 and PLK4.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/enzimologia , Proteínas de Ciclo Celular/metabolismo , Neoplasias Pulmonares/enzimologia , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Proteínas de Ciclo Celular/biossíntese , Proteínas de Ciclo Celular/genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Prognóstico , Proteínas Serina-Treonina Quinases/biossíntese , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas/biossíntese , Proteínas Proto-Oncogênicas/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transcriptoma
6.
Anticancer Res ; 40(6): 3265-3270, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32487621

RESUMO

BACKGROUND/AIM: The aim of our study was to examine miRNA-221 as a candidate biomarker to define prognosis and/or classification for glial tumors. MATERIALS AND METHODS: This study included 39 patients who underwent glial tumor surgery and 40 healthy individuals as the control group. miRNA expression levels were determined by real-time polymerase chain reaction (RT-PCR). Receiver operating characteristic curve analysis was used for analyzing the predictive ability of miRNA-221. RESULTS: The levels of miRNA-221 expression were determined by comparing the ΔCT values of miRNAs and the internal control. When the expression levels of miRNA-221 were compared according to the ΔCT method, miRNA-221 was found to be significantly increased in the patient group compared to the control group (p<0.0001). CONCLUSION: Increased expression levels of miRNA-221 could be a biomarker for glial tumors.


Assuntos
Neoplasias Encefálicas/genética , Glioblastoma/genética , MicroRNAs/biossíntese , Adulto , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/sangue , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Estudos de Casos e Controles , Feminino , Glioblastoma/sangue , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos , Masculino , MicroRNAs/sangue , MicroRNAs/genética , Prognóstico , Estudos Prospectivos
7.
Anticancer Res ; 40(6): 3203-3208, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32487614

RESUMO

BACKGROUND/AIM: We aimed to evaluate the characteristics of gastric carcinoma with high excision repair cross complementing 1 (ERCC1) expression and the prognostic value of ERCC1 expression. MATERIALS AND METHODS: ERCC1 expression was evaluated by immunohistochemistry in 309 surgically resected gastric carcinoma specimens using a tissue microarray. Cancer-related survival was analysed using competing risk analysis. RESULTS: Compared to ERCC1-low gastric carcinomas, ERCC1-high gastric carcinomas showed less local invasion (p=0.0013), lower N stage (p=0.0302), earlier pTNM stage (p=0.0003), and less frequent recurrence (p=0002). Patients with ERCC1-high gastric carcinoma showed lower cumulative incidence function estimate of cancer-related death [3.37; 95% confidence intervaI (CI)=0.89-8.75] than did those with ERCC1-low gastric carcinoma (17.12; 95% CI=12.24-22.69; p-value by Gray's test=0.0012). Adjusted proportional sub-distribution hazard ratio for cancer-related death in the patients with ERCC1-high tumour was 0.272 (95% CI=0.084-0.878; p=0.0295). CONCLUSION: High ERCC1 expression may be an independent positive prognostic marker for gastric carcinoma.


Assuntos
Proteínas de Ligação a DNA/biossíntese , Endonucleases/biossíntese , Neoplasias Gástricas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Proteínas de Ligação a DNA/genética , Endonucleases/genética , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Análise de Sobrevida , Taxa de Sobrevida , Análise Serial de Tecidos , Adulto Jovem
8.
Oncology ; 98(10): 689-698, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32585672

RESUMO

BACKGROUND: ßIII-Tubulin, encoded by the TUBB3 gene, is a microtubule protein. Several studies have shown that overexpression of TUBB3 is linked to poor prognosis and is involved in taxane resistance in some cancers. OBJECTIVE: The aim of this study was to analyze the expression and function of TUBB3 in clear cell renal cell carcinoma (ccRCC). METHODS: The expression of TUBB3 was determined using immuno-histochemistry in ccRCC specimens. The effects of TUBB3 knockdown on cell growth and invasion were evaluated in RCC cell lines. We analyzed the interaction between TUBB3, p53, cancer stem cell markers, and PD-L1. RESULTS: In 137 cases of ccRCC, immunohistochemistry showed that 28 (20%) of the ccRCC cases were positive for TUBB3. High TUBB3 expression was significantly correlated with high nuclear grade, high T stage, and N stage. A Kaplan-Meier analysis showed that high expression of TUBB3 was associated with poor overall survival after nephrectomy. In silico analysis also showed that high TUBB3 expression was correlated with overall survival. Knockdown of TUBB3 suppressed cell growth and invasion in 786-O and Caki-1 cells. High TUBB3 expression was associated with CD44, CD133, PD-L1, and p53 in ccRCC. We generated p53 knockout cells using the CRISPR-Cas9 system. Western blotting revealed that p53 knockout upregulated the expression of TUBB3. CONCLUSION: These results suggest that TUBB3 may play an oncogenic role and could be a potential therapeutic target in ccRCC.


Assuntos
Tubulina (Proteína)/biossíntese , Proteína Supressora de Tumor p53/biossíntese , Idoso , Antígeno B7-H1/biossíntese , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Processos de Crescimento Celular/fisiologia , Linhagem Celular Tumoral , Núcleo Celular/genética , Núcleo Celular/metabolismo , Feminino , Técnicas de Silenciamento de Genes , Células HEK293 , Humanos , Imuno-Histoquímica , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Prognóstico , Tubulina (Proteína)/genética , Proteína Supressora de Tumor p53/genética
9.
J Cancer Res Clin Oncol ; 146(8): 1993-2006, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32444962

RESUMO

OBJECTIVES: Kidney renal clear cell carcinoma (KIRC) is one of the most common lethal cancers in the human urogenital system. As members of the Homeobox (HOX) family, Homeobox-A (HOXA) cluster genes have been reported to be involved in the development of many cancer types. However, the expression and clinical significance of HOXA genes in KIRC remain largely unknown. MATERIALS AND METHODS: In this study, we comprehensively analyzed the mRNA expression and prognostic values of HOXA genes in KIRC using The Cancer Genome Atlas (TCGA) analysis databases online. Colony formation assay, flow cytometry and Western blot were used to detect cell proliferation, apoptosis, cell cycle, and protein level of the indicated gene. RESULTS: We found that the HOXA genes were differentially expressed in KIRC tissues when compared with normal tissues. The expression of HOXA4 and HOXA13 were significantly up-regulated, while HOXA7 and HOXA11 were down-regulated in KIRC. High mRNA levels of HOXA2, HOXA3 and HOXA13, and low level of HOXA7 predicted poor overall survival (OS) of KIRC patients. High mRNA level of HOXA13 further indicated a poor disease-free survival (DFS) of KIRC patients. Functionally, knockdown of HOXA13 significantly suppressed cell proliferation of KIRC in vitro, increased the protein level of p53 and decreased the protein level of cyclin D1 in KIRC cells. Over-expression of HOXA13 had the opposite effects on KIRC cells. CONCLUSION: Collectively, our findings suggest that HOXA13 functions as a novel oncogene in KIRC and may be a potential biomarker for this malignancy.


Assuntos
Carcinoma de Células Renais/genética , Proteínas de Homeodomínio/genética , Neoplasias Renais/genética , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Ciclina D1/metabolismo , Bases de Dados Genéticas , Regulação para Baixo , Técnicas de Silenciamento de Genes , Proteínas de Homeodomínio/biossíntese , Humanos , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Família Multigênica , Oncogenes , RNA Mensageiro/genética , Fatores de Transcrição/biossíntese , Fatores de Transcrição/genética , Transcrição Genética , Proteína Supressora de Tumor p53/metabolismo , Regulação para Cima
10.
Oncology ; 98(9): 643-652, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32434192

RESUMO

BACKGROUND: The glucose metabolism of cancer cells differs from that of noncancerous cells. Transketolase-like protein 1 (TKTL1) and glucose transporter 1 (GLUT1) both play a role in this process. These biochemical tumor markers are overexpressed in several types of human cancer. OBJECTIVE: We sought to determine if TKTL1 and/or GLUT1 expression predicts prognosis in gastric cancer. METHODS: In this retrospective study, we selected 284 patients who underwent surgery for gastric cancer at the Helsinki University Hospital. We used immunohistochemistry to assess the expression of TKTL1 and GLUT1, combined with clinicopathological data. RESULTS: Positive expression of TKTL1 was associated with positive expression of GLUT1, age over 65 years, male gender, advanced stage (II-IV), and advanced tumors (T2-T4). Patients with a positive expression of TKTL1 had a poorer prognosis than those with no expression (p = 0.042, Breslow test). GLUT1 positivity was associated with higher age and with the intestinal type of gastric cancer but did not carry any prognostic value. CONCLUSION: In conclusion, our study showed that positive expression of TKTL1 correlates with a poor prognosis in gastric cancer.


Assuntos
Transportador de Glucose Tipo 1/biossíntese , Neoplasias Gástricas/metabolismo , Transcetolase/biossíntese , Idoso , Biomarcadores Tumorais/biossíntese , Citoplasma/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Análise Serial de Tecidos
11.
J Cancer Res Clin Oncol ; 146(8): 2109-2116, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32266539

RESUMO

OBJECTIVE: To evaluate the prognostic potential of vimentin, p53, EGFR, CK5/6, CK 14, and CK 17 in patients with triple-negative breast cancer (TNBC). MATERIAL AND METHODS: Tumor specimens of 60 patients with histologically confirmed TNBC were retrospectively analyzed. Formalin-fixed paraffin-embedded blocks of the tumor tissue were used to prepare tissue microarrays (TMAs). After immune-histochemical staining, protein expression of vimentin, p53, EGFR, CK5/6, CK 14, and CK 17 was determined and the immunoreactive score (IRS) was calculated. The protein expression was correlated to overall (OS) and disease-free survival (DFS). RESULTS: Ninety percent of patients suffered from an invasive ductal carcinoma T1 or T2, 66.7% were N0, and 70% had a G3 tumor with Ki67 of > 14%. Vimentin expression was found in 28/60 patients (46.7%), p53 expression in 30/60 patients (50%), and EGFR expression in 3/60 patients (5%). CK5/6, CK14, and CK17 expression was found in 60.0%, 63.3%, and 66.7%, respectively. Vimentin expression vs no expression was associated with significantly higher mean Ki67 values (52.5% vs. 31.1%; p = 0.0013) and significantly higher p53 expression (67.9% vs. 34.4%; p = 0.0097). No significant association between vimentin expression and OS (p = 0.7710) or DFS (p = 0.5558) was found during a mean follow-up of 92 months. CONCLUSION: None of the six proteins proved to be suitable prognostic factors for OS and DSF in patients with TNBC.


Assuntos
Neoplasias de Mama Triplo Negativas/metabolismo , Vimentina/biossíntese , Biomarcadores Tumorais/biossíntese , Feminino , Humanos , Imuno-Histoquímica , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Análise Serial de Tecidos , Neoplasias de Mama Triplo Negativas/patologia
12.
J Surg Oncol ; 122(2): 243-253, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32346887

RESUMO

BACKGROUNDS AND OBJECTIVES: Recent studies have suggested that insulinoma-associated protein 1 (INSM1) is a useful marker for pathological diagnosis of pulmonary neuroendocrine tumors. In the present study, we investigated the association between INSM1 expression and prognosis in patients with pulmonary high-grade neuroendocrine carcinomas (HGNEC) and assessed the usefulness of INSM1 as a prognostic biomarker in these patients. METHODS: Seventy-five consecutive patients with HGNEC who underwent complete surgical resections from January 2000 to December 2018 were enrolled in this study. We classified these patients into two groups: the INSM1-positive group (n = 59) and INSM1-negative group (n = 16). We compared the clinicopathological characteristics, overall survival (OS), and recurrence-free survival (RFS) between the groups. In addition, we performed univariate and multivariate analyses to identify the prognostic factors associated with postoperative survival. RESULTS: Significant differences in tumor diameter and vascular invasion between the groups were found. OS and RFS were significantly poorer in the INSM1-positive group than in the INSM1-negative group. Univariate and multivariate analyses revealed that INSM1 expression was the strongest predictor of poor prognosis for OS and RFS. CONCLUSIONS: INSM1 expression had the greatest influence on the prognosis in patients with HGNEC and may be a prognostic biomarker in these patients.


Assuntos
Carcinoma Neuroendócrino/metabolismo , Carcinoma Neuroendócrino/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Proteínas Repressoras/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/biossíntese , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Prognóstico , Taxa de Sobrevida
13.
Pediatr Surg Int ; 36(6): 727-734, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32222813

RESUMO

BACKGROUND: SALL4 is a zinc finger transcription factor that exerts its physiological role during embryo-fetal development. Analyses of SALL4 expression have shown its oncogenic role in precursor B-cell lymphoblastic lymphoma, acute and chronic myeloid leukemia, gastrointestinal, breast, and lung cancers. The aim of this study was to determine the immunohistochemical profile of SALL4 in pediatric yolk sac tumors (YSTs). METHODS AND RESULTS: Immunohistochemistry detection of SALL4 was performed in 22 cases of pediatric YSTs and 10 mature teratomas. The percentage of tumor cells stained was scored as 0, 1+ (1-30% cells), 2+ (31-60%), 3+ (61-90%), and 4+ (> 90%). To compare its sensitivity and specificity with Glypican-3 and α-fetoprotein (AFP), we also stained tumors from these cases for Glypican-3 and AFP. In contrast to AFP and glypican-3, SALL4 staining in more than 90% of the tumor cells was seen in all 22 pediatric YSTs (100% sensitivity) (P < 0.001 for both SALL4 vs. AFP and SALL4 vs. glypican-3). CONCLUSIONS: SALL4 is a sensitive marker for pediatric YSTs and it can be used to distinguish them from mature teratomas. SALL4 is likely to become a new and valuable biomarker for the diagnosis of pediatric YST.


Assuntos
Tumor do Seio Endodérmico/metabolismo , Neoplasias Ovarianas/metabolismo , Neoplasias Testiculares/metabolismo , Fatores de Transcrição/biossíntese , Biomarcadores Tumorais/biossíntese , Criança , Tumor do Seio Endodérmico/patologia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Neoplasias Ovarianas/patologia , Neoplasias Testiculares/patologia
14.
Arch Pathol Lab Med ; 144(3): 290-304, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32101059

RESUMO

CONTEXT.­: Immunohistochemistry (IHC) has become increasingly important in the evaluation of pathologic conditions in the genitourinary (GU) organs. In addition to careful evaluation of hematoxylin-eosin sections and generation of a differential diagnosis, choosing the optimal panel of IHC markers becomes even more important when the biopsy material is very limited. The following summary of our experience supplemented with relevant literature review exemplifies how to use IHC to facilitate pathologic diagnosis in the GU system. OBJECTIVE.­: To describe our experience with the most common immunohistochemical markers used in GU pathology. DATA SOURCES.­: Institutional experience and literature search comprise our data sources. CONCLUSIONS.­: Application of IHC provides enormous benefits to the interpretation of GU pathologic conditions, including benign and malignant lesions. However, both insufficient and excessive types of use of IHC, as well as incorrect interpretations in common and rare GU conditions, could present pitfalls in diagnosis.


Assuntos
Biomarcadores Tumorais/biossíntese , Imuno-Histoquímica/métodos , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Neoplasias da Próstata/diagnóstico , Neoplasias Testiculares/diagnóstico , Neoplasias Urogenitais/diagnóstico , Diagnóstico Diferencial , Humanos , Masculino , Neoplasias Embrionárias de Células Germinativas/metabolismo , Neoplasias da Próstata/metabolismo , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Neoplasias Testiculares/metabolismo , Neoplasias Urogenitais/metabolismo
15.
J Cancer Res Clin Oncol ; 146(4): 821-841, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32103339

RESUMO

PURPOSE: Lung cancer has the highest morbidity and mortality among all cancer types. Reliable prognostic biomarkers are needed to identify high-risk patients apart from TNM system for precision medicine. The present study is designed to identify robust prognostic biomarkers in lung adenocarcinoma (LUAD) based on integration of multiple GEO datasets, The Cancer Genome Atlas (TCGA) database and Clinical Proteomic Tumor Analysis Consortium (CPTAC) database. METHODS: Four LUAD GEO datasets (GSE10072, GSE2514, GSE43458, and GSE32863) and TCGA database were implemented to analyze the differently expressed genes (DEGs). Gene ontology, KEGG pathway, and protein-protein interaction network (PPI) were conducted based on the above DEGs. Hub genes were selected based on connectivity degree in the PPI network. Expression analysis and Kaplan-Meier survival analysis were conducted in CPTAC lung adenocarcinomas cohort. Kaplan-Meier survival analysis and Cox proportional hazards regression were performed on these hub genes using TCGA and our own cohort. RESULTS: A total of 430 shared genes in all five datasets were identified as DEGs. Based on their PPI network, nine hub genes were selected and all of them were significantly associated with overall survival using GEPIA analysis. Two hub genes, TOP2A and UBE2C, were further combined and showed poorer prognosis in both TCGA dataset and our validated cohort. Analysis in CPTAC revealed that TOP2A and UBE2C were significantly highly expressed in tumor sample. Multivariable analysis suggested TOP2A and UBE2C as independent prognostic factors in LUAD. CONCLUSION: Using data mining approach, we identified TOP2A and UBE2C as two robust prognostic factors in LUAD. We also demonstrated the TOP2A/UBE2C co-expression status in LUAD, and TOP2A/UBE2C co-expression correlated with poorer prognosis. More in-depth research is needed for transforming this result into clinical setting.


Assuntos
Adenocarcinoma de Pulmão/enzimologia , Adenocarcinoma de Pulmão/genética , DNA Topoisomerases Tipo II/biossíntese , Proteínas de Ligação a Poli-ADP-Ribose/biossíntese , Enzimas de Conjugação de Ubiquitina/biossíntese , Adenocarcinoma de Pulmão/cirurgia , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Estudos de Coortes , Biologia Computacional , DNA Topoisomerases Tipo II/genética , Mineração de Dados , Bases de Dados Genéticas , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Proteínas de Ligação a Poli-ADP-Ribose/genética , Prognóstico , Taxa de Sobrevida , Análise Serial de Tecidos , Transcriptoma , Enzimas de Conjugação de Ubiquitina/genética
16.
Cancer Control ; 27(1): 1073274819901170, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32077330

RESUMO

As p53-binding protein 1 (53BP1) localizes to the sites of DNA double-strand breaks and rapidly forms nuclear foci (NF), and its presence may be an indicator of endogenous genomic instability (GIN). We previously showed that 53BP1 NF in cervical cells increase with neoplastic progression, indicating the significance of 53BP1 expression for the estimation of malignant potential during cervical carcinogenesis. This study aimed to further elucidate the impact of 53BP1 expression as a biomarker for cervical squamous intraepithelial lesion (SIL). A total of 81 tissue samples, including 17 of normal cervical epithelium, 22 of cervical intraepithelial neoplasia (CIN) 1, 21 of CIN2, and 21 of CIN3, from patients positive for high-risk human papillomavirus (HR-HPV) were used for double-label immunofluorescence of 53BP1 and Ki-67/p16INK4a expression and HR-HPV in situ hybridization. We analyzed associations between 53BP1 expression type with parameters such as CIN grade, HR-HPV infection status, p16INK4a expression, and CIN prognosis. Expression type of 53BP1 was significantly associated with histological grade of CIN and HR-HPV in situ hybridization signal pattern (P < .0001). There was a significant correlation between 53BP1 and p16INK4a expression levels (r = .73, P < .0001). However, there was no association between 53BP1 expression type and CIN prognosis. We propose that 53BP1 expression type is a valuable biomarker for SIL, which can help estimate the grade and GIN of cervical lesions reflecting replication stress caused by the integration of HR-HPV to the host genome.


Assuntos
Inibidor p16 de Quinase Dependente de Ciclina/biossíntese , Infecções por Papillomavirus/metabolismo , Lesões Intraepiteliais Escamosas/metabolismo , Lesões Intraepiteliais Escamosas/virologia , Proteína 1 de Ligação à Proteína Supressora de Tumor p53/biossíntese , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/virologia , Adulto , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Feminino , Humanos , Papillomaviridae/genética , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Lesões Intraepiteliais Escamosas/genética , Lesões Intraepiteliais Escamosas/patologia , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Proteína 1 de Ligação à Proteína Supressora de Tumor p53/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia
17.
Int J Mol Sci ; 21(4)2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32098071

RESUMO

Mismatch repair (MMR) analysis in breast cancer may help to inform immunotherapy decisions but it lacks breast-specific guidelines. Unlike in other neoplasms, MMR protein loss shows intra-tumor heterogeneity and it is not mirrored by microsatellite instability in the breast. Additional biomarkers can improve MMR clinical testing. Phosphatase and tensin homolog (PTEN) inactivation is an early oncogenic event that is associated with MMR deficiency (dMMR) in several tumors. Here, we sought to characterize the diagnostic utility of PTEN expression analysis for MMR status assessment in breast cancer. A total of 608 breast cancers were profiled for their MMR and PTEN status. Proteins expression and distribution were analyzed by immunohistochemistry (IHC) on tissue microarrays and confirmed on full sections; PTEN copy number alterations were detected using a real-time PCR assay. Overall, 78 (12.8%) cases were MMR-heterogeneous (hMMR), while all patterns of PTEN expression showed no intra-tumor heterogeneity. Wild-type PTEN expression was observed in 15 (18.5%) dMMR tumors (p < 0.0001). Survival analyses revealed significant correlations between MMR-proficient (pMMR), PTEN expression, and a better outcome. The positive predictive value of PTEN-retained status for pMMR ranged from 94.6% in estrogen receptor (ER)+/HER2- tumors to 100% in HER2-amplified and ER-/HER2- cases. We propose a novel diagnostic algorithm where PTEN expression analysis can be employed to identify pMMR breast cancers.


Assuntos
Biomarcadores Tumorais/biossíntese , Neoplasias da Mama , Reparo de Erro de Pareamento de DNA , Regulação Neoplásica da Expressão Gênica , PTEN Fosfo-Hidrolase/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Taxa de Sobrevida
18.
Int J Mol Sci ; 21(4)2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32098271

RESUMO

Members of the polypeptide N-acetylgalactosaminyltransferase (GALNT) family function as the initiating enzymes that catalyze mucin-type O-glycosylation of proteins, and their dysregulated expression can alter cancer cell behaviors such as de novo occurrence, proliferation, migration, metastasis, and drug resistance. Recent studies have demonstrated that one of the family's members, GALNT14, is aberrantly expressed in multiple cancers and involved in a variety of biological functions. Moreover, the single nucleotide polymorphisms (SNPs) of GALNT14-rs9679162 have been shown to predict therapeutic outcomes in patients with hepatocellular carcinoma as well as several other different types of gastrointestinal cancer. This review summarizes the structural features of GANLT14, its functional roles, and the predictive values of GALNT14 genotypes and enzyme levels in multiple cancers receiving distinct anticancer therapies.


Assuntos
Biomarcadores Tumorais , Genótipo , N-Acetilgalactosaminiltransferases , Proteínas de Neoplasias , Neoplasias , Polimorfismo de Nucleotídeo Único , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Humanos , N-Acetilgalactosaminiltransferases/biossíntese , N-Acetilgalactosaminiltransferases/genética , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Neoplasias/enzimologia , Neoplasias/genética , Neoplasias/patologia , Neoplasias/terapia
19.
Sci Rep ; 10(1): 1243, 2020 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-31988315

RESUMO

The prognostic impact of tumoral programmed death-ligand 1 (PD-L1) expression in correlation with neutrophil-to-lymphocyte ratio (NLR) was retrospectively assessed in 83 patients with completely resected stage I squamous cell carcinoma of the lung, as PD-L1 is a potent regulator of cancer immunity and NLR is a potential surrogate of immune status. Forty-three patients (51.8%) had tumor with positive PD-L1 expression. There was no significant correlation between PD-L1 expression and NLR. PD-L1-positivity failed to provide a significant prognostic impact (overall survival [OS] rate at 5 years, 53.0% in PD-L1-positive patients versus 70.1% in PD-L1-negative patients; P = 0.117). Among NLR-low (<2.2) patients, however, PD-L1-positivity was significantly correlated with a poor prognosis (OS rate at 5 years, 46.1% versus 86.0%; P = 0.020). In contrast, among NLR-high (≥2.2) patients, PD-L1-positivity provided no prognostic impact (P = 0.680). When NLR status and tumoral PD-L1 status were combined, "NLR-low and PD-L1-negative" was a significant and independent factor to predict a favorable recurrence-free survival (hazard ratio, 0.237 [95% confidence interval, 0.083 to 0.674]; P = 0.007) and OS (hazard ratio, 0.260 [0.091 to 0.745]; P = 0.012). These results suggest the prognostic impact of tumoral PD-L1 expression might be influenced by the status of NLR.


Assuntos
Antígeno B7-H1/biossíntese , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma de Células Escamosas/imunologia , Neoplasias Pulmonares/imunologia , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/genética , Antígeno B7-H1/imunologia , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/imunologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Linfócitos/imunologia , Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/imunologia , Neutrófilos/patologia , Prognóstico , Curva ROC , Estudos Retrospectivos , Análise de Sobrevida , Transcriptoma
20.
FASEB J ; 34(1): 1481-1496, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31914615

RESUMO

As the key factor of the polarity protein complex, Par6 not only regulates polarization processes, but also plays important roles in tumor metastasis and progression in many epithelium malignancy tumors. Here, we showed that Par6 is an essential component in glioma tumorigenesis. Our results indicated the aberrant expression of Par6 in malignant glioma tissues and cell lines. We found that the regulation of Par6 expression induces cell proliferation and tumor growth in vivo and in vitro. Additionally, RNA-seq revealed the effects of Par6 were associated with cyclin D1-regulated cell cycle progression in glioma cells. Moreover, our results demonstrated that the regulation of Par6 can enhance the activation of Akt/PI3K signaling pathway, and subsequently upregulate the expression level of GSK-3ß protein, which then regulate cyclin D1-mediated cell cycle regulation. Furthermore, we found that TGF-ß-induced the upregulation of Par6 expression may be involved in this process. The pathological analysis confirmed the correlation between Par6 expression and the prognosis in human glioma tissues, suggesting the regulation of Par6 expression regulates glioma tumorigenesis and progression. Thus, our findings showed that Par6 might be a potential biomarker for the diagnosis and providing a therapeutic strategy for the treatment of malignant glioma.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/biossíntese , Biomarcadores Tumorais/biossíntese , Ciclo Celular , Regulação Neoplásica da Expressão Gênica , Glioma/metabolismo , Transdução de Sinais , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Ciclina D1/genética , Ciclina D1/metabolismo , Glioma/genética , Glioma/patologia , Glicogênio Sintase Quinase 3 beta/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Masculino , Camundongos , Camundongos Nus , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo
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