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Developmental and epileptic encephalopathy (DEE) is a severe encephalopathy in infants and early childhood. In this study we reported a recurrent de novo variant (c.3985C>T, p.R1330W) in HECW2 (HECT, C2 and WW domain containing E3 ubiquitin protein ligase 2) (MIM# 617245) identified by screening 240 patients with DEE and summarized clinical features of published DEE patients with HECW2 variants. Functionally, transcriptional knockdown of zebrafish hecw2a led to early morphological abnormalities in the brain tissues. These results suggest a potential functional link between HECW2 dysfunction and brain development.
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Encefalopatias/genética , Deficiência Intelectual/genética , Ubiquitina-Proteína Ligases/genética , Proteínas de Peixe-Zebra/genética , Adolescente , Animais , Encefalopatias/epidemiologia , Encefalopatias/patologia , Criança , Pré-Escolar , Modelos Animais de Doenças , Predisposição Genética para Doença , Humanos , Lactente , Deficiência Intelectual/epidemiologia , Deficiência Intelectual/patologia , Masculino , Mutação/genética , Sequenciamento do Exoma , Peixe-Zebra/genéticaRESUMO
Echinococcosis is a worldwide neglected zoonotic disease. Alveolar echinococcosis (AE) poses a more serious threat to life and health than cystic echinococcosis, and has been one of the world's most lethal chronic parasitosis. Assessment of metacestode activity status is essential for individual treatment strategy design for a given AE patient, and fluorodeoxyglucose positron-emission tomography (FDG-PET) has been the gold standard. In this study, we reviewed previous evidence on AE activity assessment using contrast-enhanced ultrasound (CEUS), and its comparison with FDG-PET. The results showed good consistency between them, indicating CEUS as a suitable substitute for FDG-PET. With its advantage as being readily portable, widely available, and not costly, CEUS is more suitable for use in the developing countries and rural areas.
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Equinococose Hepática , Equinococose , Equinococose/diagnóstico por imagem , Equinococose Hepática/diagnóstico por imagem , Fluordesoxiglucose F18 , Humanos , Tomografia por Emissão de Pósitrons , UltrassonografiaRESUMO
The pretreatment nutritional and immunological status play indispensable roles in predicting the outcome of patients with various types of malignancies. The aim of the study was to investigate whether preoperative prognostic nutritional index (PNI), which simply accounts for nutritional and immunological status, was associated with overall survival (OS) in patients with gallbladder carcinoma (GBC). The retrospective study included a total of 315 GBC patients after surgery between 2002 and 2012. PNI was calculated according to the following formula: 10× serum albumin (g/dl) +0.005× total lymphocyte count (per mm3). A receiver operating characteristic (ROC) curve for survival prediction was plotted to verify the optimal cutoff value for LMR, which was set at 46.14. According the value, patients were categorized into two different groups, namely high-PNI group (n = 133) and low-PNI group (n = 182). The univariate and multivariate Cox regression models were used to identify the independent prognostic factors. The results showed that low pretreatment PNI value was significantly associated with elderly age, partial surgery procedure, and advanced tumor status such as tumor stage, node stage, and tumor-node-metastasis stage (P < 0.05). The low-PNI group had a worse OS compare with the high-PNI group (P < 0.05). Via univariate and multivariate analyses, pretreatment PNI was identified as an independent prognostic factor for OS [HR: 0.613; 95%CI: 0.448-0.838; P < 0.001]. Subgroup analyses further revealed that PNI was significantly associated with postoperative OS independent of tumor node metastasis stage and surgical procedure. In conclusion, pretreatment PNI might serve as an effective predictor to evaluate prognosis of GBC patients after surgery. Based on the findings, PNI, characterized with accessibility, objectivity and noninvasiveness, should be included in the routine assessment of GBC.
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AIM: Forkhead box M1 (FoxM1) is a transcription factor that plays important roles in the pathogenesis and progression of human cancers, including hepatocellular carcinoma (HCC). The aim of this study was to examine the involvement of FoxM1 in the anti-cancer action of sorafenib, a multikinase inhibitor, in human HCC cells. METHODS: HCC cell lines HepG2 and HuH-7 were tested. Cell viability was examined using MTT assay and cell invasion was determined with Transwell migration assay. The relevant mRNA expression was determined with RT-PCR, and the proteins were detected using Western blotting and immunofluorescence assays. RNA interference was used to modify the expression of p53 and FoxM1. HuH-7 cell line xenograft mice were used for in vivo study, which were treated with sorafenib (40 mg/kg, po) daily for 3 weeks. RESULTS: Sorafenib (2-20 µmol/L) inhibited the proliferation of the cells in dose- and time-dependent manners with an IC50 value of nearly 6 µmol/L at 48 h. Sorafenib (6 µmol/L) markedly suppressed the cell invasion. Furthermore, sorafenib (2-6 µmol/L) dose-dependently decreased the expression of FoxM1, MMP-2, and Ki-67, and up-regulated that of p53 in the cells. Silencing p53 abolished the decrease of FoxM1 and increase of p53 in sorafenib-treated cells. Silencing FoxM1 significantly reduced the expression of MMP-2 and Ki-67, and enhanced the anti-proliferation action of sorafenib in the cells, whereas overexpression of FoxM1 increased the expression of MMP-2 and Ki-67, and abrogated the anti-proliferation action of sorafenib. In the xenograft mice, sorafenib administration decreased the tumor growth by 40%, and markedly increased the expression of p53, and decreased the expression of FoxM1, MMP-2, and Ki-67 in tumor tissues. CONCLUSION: Sorafenib inhibits HCC proliferation and invasion by inhibiting MMP-2 and Ki-67 expression due to up-regulation of P53 and suppressing FoxM1.
Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Fatores de Transcrição Forkhead/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Niacinamida/análogos & derivados , Compostos de Fenilureia/farmacologia , Proteína Supressora de Tumor p53/metabolismo , Regulação para Cima/efeitos dos fármacos , Animais , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proteína Forkhead Box M1 , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Knockout , Camundongos Nus , Invasividade Neoplásica/patologia , Niacinamida/farmacologia , SorafenibeRESUMO
Protein ubiquitination plays vital roles in regulating various cytobiological processes such as cell cycle progression, DNA damage repair, signal transduction and membrane localization of various proteins. Moreover, proteins can be modified by single ubiquitin molecules (monoubiquitination) or ubiquitin chains (polyubiquitination). Polyubiquitination regulates protein function by linking different types of polyubiquitin chains to substrates. All the 7 known linkage types of polyubiquitination are inter-ubiquitin linkages formed through lysine residues. In recent years, the eighth ubiquitin linkage type, linear ubiquitination in which the linkages are formed between the amino group of methionine residues of ubiquitin and the carboxy group of glycine residues of another, has been identified. Studies have shown that linear ubiquitination plays very important roles in various processes including innate immunity and inflammatory reactions. The ubiquitin ligase E3 that recruits linear ubiquitin chains is called linear ubiquitin chain assembly complex (LUBAC), however, little is known about its constitutive substrates, activity regulation and functions. Here we reviewed the mechanism of activity regulation of ubiquitin ligases, deubiquitinating enzymes and substrates as well as their roles in multiple areas including innate immunity, and also analyzed future directions to provide references for relevant studies.
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Ubiquitina/metabolismo , Animais , Endopeptidases/fisiologia , Humanos , Imunidade Inata , NF-kappa B/fisiologia , Transdução de Sinais/fisiologia , Ubiquitina-Proteína Ligases/fisiologia , UbiquitinaçãoRESUMO
The development of mammalian kidney is a complex process. The reciprocal inductive interactions between epithelial cells and metanephric mesenchymal cells determine cell fates including proliferation, growth, apoptosis, and eventually contribute to the formation of an intact kidney. Multiple signaling pathways, including the GDNF/Ret, Wnt and BMP signaling pathways, have been shown to regulate the development of kidney. A myriad of signaling pathways and their cross-talks form a precise spatiotemporal regulatory network, which ensures the kidney to be properly organized. In this review, we summarize the physiological process of kidney development as well as the involved signaling pathways and their interplay.
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Rim/crescimento & desenvolvimento , Rim/metabolismo , Transdução de Sinais , Animais , Humanos , Organogênese , Proteínas/metabolismoRESUMO
BACKGROUND: To explore the efficacy of microwave ablation (MWA) in the treatment of hepatic alveolar echinococcosis (HAE) with a diameter of ≤5 cm. METHOD: From June 2014 to January 2020, patients diagnosed with HAE were retrospectively analyzed. After balancing the confounding factors by propensity score matching (PSM) , the patients were divided into MWA group (n = 20) and radical operation group (n = 20) by 1:1 matching. The safety and effectiveness of MWA were assessed by comparing the differences between the two groups in terms of postoperative general laboratory indices, grading of postoperative complications, length of postoperative hospitalization, the outcome of treatment, and disease recurrence. RESULT: After PSM, all confounders were not statistically different (P>0.05) . Compared with the radical surgery group, patients in the MWA group had lower postoperative ALT and WBC elevations (P<0.001) , shorter postoperative hospital stay (P<0.001) ) , lower hospital costs (P<0.001) . The effective rate of the two groups was 100%. There was no statistical difference in the incidence of postoperative complications and recurrence rate (P>0.05). CONCLUSION: MWA is a safe and effective means of treating HAE ≤ 5 cm in diameter.
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Equinococose Hepática , Neoplasias Hepáticas , Ablação por Radiofrequência , Equinococose Hepática/cirurgia , Humanos , Neoplasias Hepáticas/terapia , Micro-Ondas/uso terapêutico , Pontuação de Propensão , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Background: Numerous studies have indicated that the neddylation pathway is closely associated with tumor development. MLN4924 (Pevonedistat), an inhibitor of the NEDD8-activating E1 enzyme, is considered a promising chemotherapeutic agent. Recently, we demonstrated that neddylation of the tumor suppressor PTEN occurs under high glucose conditions and promotes breast cancer development. It has been shown, however, that PTEN protein levels are reduced by 30-40% in breast cancer. Whether this PTEN deficiency affects the anti-tumor function of MLN4924 is unknown. Methods: In the present study, cell counting kit-8 and colony formation assays were used to detect cell proliferation, and a transwell system was used to quantify cell migration. A tumor growth assay was performed in BALB/c nude mice. The subcellular location of PTEN was detected by fluorescence microscopy. The CpG island of the UBA3 gene was predicted by the Database of CpG Islands and UCSC database. Western blotting and qRT-PCR were used to measure the expression of indicated proteins. The Human Protein Atlas database, the Cancer Genome Atlas and Gene Expression Omnibus datasets were used to validate the expression levels of UBA3 in breast cancer. Results: Our data show that the anti-tumor efficacy of MLN4924 in breast cancer cells was markedly reduced with the deletion of PTEN. PI3K/Akt signaling pathway activity correlated positively with UBA3 expression. Pathway activity correlated negatively with NEDP1 expression in PTEN-positive breast cancer patients, but not in PTEN-negative patients. We also demonstrate that high glucose conditions upregulate UBA3 mRNA by inhibiting UBA3 promoter methylation, and this upregulation results in the overactivation of PTEN neddylation in breast cancer cells. Conclusion: These data suggest a mechanism by which high glucose activates neddylation. PTEN is critical, if not indispensable, for MLN4924 suppression of tumor growth; PTEN status thus may help to identify MLN4924-responsive breast cancer patients.
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Inactivation of tumor suppressor gene is a key event in carcinogenesis. p53 is one of the most important tumor suppressor genes in the genome, and its mutations are found in approximately 50% of human cancers. p53 mutation is also the main cause for human Li-Fraumeni syndrome. The vast majority of p53 mutations are missense mutations, and the corresponding mutant p53 proteins not only lose wild-type p53 tumor suppressor activities, but also gain new oncogenic properties favoring cancer development. Here, we mainly discussed the structural and functional alterations of mutant p53, the molecular mechanisms underlying gain of oncogenic functions, and the strategies and explorations of suppressing mutant p53 activities.
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Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Humanos , Modelos Biológicos , Mutação , Mutação de Sentido Incorreto , Neoplasias/etiologia , Neoplasias/genética , Neoplasias/metabolismo , Proteína Supressora de Tumor p53/fisiologiaRESUMO
Site- and state-specific lysine methylation of histones is catalyzed by a family of proteins including those contain the evolutionarily conserved SET domain. Research on histone methyltransferases is a part of epigenetics, which plays a fundamental role in heterochromatin formation, X-chromosome inactivation and transcription regulation. Aberrant histone methylation was linked to a number of developmental disorders and human disease including several carcinomas. Histone lysine methylation is a functionally complex process, as it can either activate or repress transcription, depending on sequence-specific lysine methylation site in histones. Non-histone proteins were found to be methylated by SET domain-containing histone methyltransferases whose primary targets were presumed to be histones. The researches on histone methyltransferases will make a completely new space for transcriptional activity, embryonic development, cell differentiation, and signal transduction.
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Histonas/metabolismo , Proteínas Metiltransferases/metabolismo , Carcinoma/genética , Carcinoma/metabolismo , Carcinoma/patologia , Histona Metiltransferases , Histona-Lisina N-Metiltransferase , Humanos , Metilação , Modelos Biológicos , Proteínas Metiltransferases/química , Proteínas Metiltransferases/genética , Estrutura Terciária de Proteína , Proteína Supressora de Tumor p53/metabolismoRESUMO
RATIONALE: Hepatic alveolar echinococcosis (HAE) is a potentially fatal and chronically progressive infestation that is caused by the multivesicular metacestode of Echinococcus multilocularis (EM). HAE behaves like a malignant tumor and has been referred to as "worm cancer." The main treatment method for HAE is surgical resection. PATIENT CONCERNS: We present a 41-year-old Tibetan alveolar echinococcosis (AE) patient with AE lesions invading the right liver lobe and retrohepatic inferior vena cava (RHIVC). DIAGNOSES: The patient was diagnosed with HAE based on results obtained from ultrasound examination, computed tomography, liver 3-dimensional reconstruction, serology tests, clinical presentation, and surgical exploration. The final pathology report confirmed the diagnosis as HAE. INTERVENTIONS: A radical surgery that combined resection of the liver and RHIVC was performed successfully. OUTCOMES: The patient had an uneventful postoperative recovery and a good prognosis. LESSONS: When lesions of the liver significantly violate the RHIVC, resecting the RHIVC without reconstruction may be considered if possible.
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Equinococose Hepática/cirurgia , Hepatectomia/métodos , Fígado/cirurgia , Veia Cava Inferior/cirurgia , Adulto , Equinococose , Equinococose Hepática/diagnóstico por imagem , Edema/etiologia , Edema/terapia , Hepatectomia/efeitos adversos , Humanos , Extremidade Inferior , Masculino , Derrame Pleural/etiologia , Derrame Pleural/terapia , Complicações Pós-Operatórias/terapia , EscrotoRESUMO
The zinc finger proteins containing the Kruppel-associated box domain (KRAB) constitute the largest single family of transcriptional regulators in mammals. Many genes encoding members of this family are arranged in clusters. KRAB-containing proteins are characterized by the presence of 4 and over 30 C2H2 zinc-finger motifs and a KRAB domain near the amino terminus of the protein. KRAB domain behaving as a protein-protein interaction domain could bind to corepressor proteins and/or transcription factors, and that the KRAB-containing proteins could act as a repressor or corepressor and play a key role in transcriptional repression. Members of the family are involved in embryonic development, cell differentiation, cell proliferation, apoptosis, neoplastic transformation and cell cycle regulation.
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Fatores de Transcrição Kruppel-Like/química , Fatores de Transcrição Kruppel-Like/metabolismo , Dedos de Zinco , Sequência de Aminoácidos , Animais , Fenômenos Fisiológicos Celulares , Cromossomos Humanos/metabolismo , Humanos , Fatores de Transcrição Kruppel-Like/genética , Dados de Sequência Molecular , Estrutura Terciária de ProteínaRESUMO
The GSDMDC family,a novel protein superfamily, includes five members (DFNA5, DFNA5L, GSDM, GSDML and MLZE), all of them containing a Gasdermin domain. Many studies indicated that the GSDMDC family had many important physiological functions in development, tumorigenesis and genetic disease with deafness and hair loss phenotype. Many studies have focused on the DFNA5 gene because it is one of the disease genes of autosomal dominant non-syndromic hearingimpairment and it is also associated with melanoma and breast cancer. But it is still unclear of the molecular mechanism of DFNA5 in the genetic disease and tumorigenesis. And there are also few studies on the spatial structure , interacting proteins and physiological functions of the GSDMDC domain. So there are a lot of works to do for shedding light on the physiological functions and the relevance on genetic disease of the other members of the GSDMDC family.
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Família Multigênica , Proteínas de Neoplasias/metabolismo , Animais , Surdez/genética , Surdez/metabolismo , Doenças Genéticas Inatas/genética , Doenças Genéticas Inatas/metabolismo , Humanos , Proteínas de Neoplasias/química , Proteínas de Neoplasias/genética , Neoplasias/genética , Neoplasias/metabolismo , Estrutura Terciária de ProteínaRESUMO
RNA interference (RNAi) has been extensively used for sequence-specific silencing of gene function in C. elegans, Drosophila, mouse and rat. The generation of RNAi transgenic mice made it possible to knock down gene expression at the whole organism level in mammalian species. In this review we described the design strategy of RNAi vectors, compared the difference of gene knock-down from knock-out, and summarized the advantages and unresolved issues concerning RNAi transgenic mice. The contribution of RNAi transgenic mice to functional genomics and of its prospect for application were also discussed.
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Técnicas de Silenciamento de Genes/métodos , Camundongos Transgênicos/genética , Interferência de RNA/fisiologia , Animais , Camundongos , Modelos BiológicosRESUMO
BACKGROUND: Current cancer therapy mainly focuses on identifying novel targets crucial for tumorigenesis. The FoxM1 is of preference as an anticancer target, due to its significance in execution of mitosis, cell cycle progression, as well as other signal pathways leading to tumorigenesis. FoxM1 is partially regulated by oncoproteins or tumor suppressors, which are often mutated, lost, or overexpressed in human cancer. Since sustaining proliferating signaling is an important hallmark of cancer, FoxM1 is overexpressed in a series of human malignancies. Alarge- scale gene expression analysis also identified FoxM1 as a differentially-expressed gene in most solid tumors. Furthermore, overexpressed FoxM1 is correlated with the prognosis of cancer patients, as verified in a series of malignancies by Cox regression analysis. Thus, extensive studies have been conducted to explore the roles of FoxM1 in tumorigenesis, making it an attractive target for anticancer therapy. Several antitumor drugs have been reported to target or inhibit FoxM1 expression in different cancers, and down-regulation of FoxM1 also abrogates drug resistance in some cancer cell lines, highlighting a promising future for FoxM1 application in the clinic.
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Antineoplásicos/uso terapêutico , Transformação Celular Neoplásica/genética , Fatores de Transcrição Forkhead/biossíntese , Fatores de Transcrição Forkhead/genética , Neoplasias/tratamento farmacológico , Proliferação de Células/genética , Resistencia a Medicamentos Antineoplásicos/genética , Proteína Forkhead Box M1 , Regulação Neoplásica da Expressão Gênica , Humanos , Mitose/genética , Transdução de Sinais/genéticaRESUMO
PURPOSE: To evaluate the prognostic value of alkaline phosphatase (ALP) and gamma-glutamyltransferase (GGT) in gallbladder cancer (GBC). MATERIALS AND METHODS: Serum ALP and GGT levels and clinicopathological parameters were retrospectively evaluated in 199 GBC patients. Receiver operating characteristic (ROC) curve analysis was performed to determine the cut-off values of ALP and GGT. Then, associations with overall survival were assessed by multivariate analysis. Based on the significant factors, a prognostic score model was established. RESULTS: By ROC curve analysis, ALP≥210 U/L and GGT≥43 U/L were considered elevated. Overall survival for patients with elevated ALP and GGT was significantly worse than for patients within the normal range. Multivariate analysis showed that the elevated ALP, GGT and tumor stage were independent prognostic factors. Giving each positive factor a score of 1, we established a preoperative prognostic score model. Varied outcomes would be significantly distinguished by the different score groups. By further ROC curve analysis, the simple score showed great superiority compared with the widely used TNM staging, each of the ALP or GGT alone, or traditional tumor markers such as CEA, AFP, CA125 and CA199. CONCLUSIONS: Elevated ALP and GGT levels were risk predictors in GBC patients. Our prognostic model provides infomration on varied outcomes of patients from different score groups.
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Fosfatase Alcalina/sangue , Neoplasias da Vesícula Biliar/sangue , Neoplasias da Vesícula Biliar/patologia , Modelos Biológicos , gama-Glutamiltransferase/sangue , Idoso , Área Sob a Curva , Antígeno Ca-125/sangue , Antígeno CA-19-9/sangue , Antígeno Carcinoembrionário/sangue , Feminino , Neoplasias da Vesícula Biliar/enzimologia , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Curva ROC , Estudos Retrospectivos , Taxa de Sobrevida , alfa-Fetoproteínas/metabolismoRESUMO
BACKGROUND: To compare the clinicopathological features and prognosis between younger and aged patients with hepatocellular carcinoma (HCC). METHODS: We analyzed the outcome of 451 HCC patients underwent liver resection, transcatheter arterial chemoembolization and radiofrequency ablation, respectively. Then risk factors for aged and younger patients' survival were evaluated by multivariate analysis, respectively. RESULTS: The patients who were older than 55 years old were defined as the older group. The overall survival for aged patients was significantly worse than those younger patients. The younger patients had similar liver functional reserve but more aggressive tumor factors than aged patients. Cox regression analysis showed that the elevated levels of aspartate aminotransferase (AST) (Wald χ2 = 3.963, P = 0.047, hazard ratio [HR] =1.453, 95% confidence interval [CI]: 1.006-2.098), lower albumin (Wald χ2 = 12.213, P < 0.001, HR = 1.982, 95% CI: 1.351-2.910), tumor size (Wald χ2 = 8.179, P = 0.004, HR = 1.841, 95% CI: 1.212-2.797), and higher alpha-fetoprotein level (Wald χ2 = 4.044, P = 0.044, HR = 1.465, 95% CI: 1.010-2.126) were independent prognostic factors for aged patients, while only elevated levels of AST (Wald χ2 = 14.491, P < 0.001, HR = 2.285, 95% CI: 1.493-3.496) and tumor size (Wald χ2 = 21.662, P < 0.001, HR = 2.928, 95% CI: 1.863-4.604) were independent prognostic factors for younger patients. CONCLUSIONS: Age is a risk factor to determine the prognosis of patients with HCC. Aged patients who have good liver functional reserve are still encouraged to receive curative therapy.
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Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/mortalidade , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Adulto JovemRESUMO
AIM: To preliminarily investigate the prognostic significance of the platelet to lymphocyte ratio (PLR) in patients with gallbladder carcinoma (GBC). METHODS: Clinical data of 316 surgical GBC patients were analyzed retrospectively, and preoperative serum platelet and lymphocyte counts were used to calculate the PLR. The optimal cut-off value of the PLR for detecting death was determined by the receiver operating characteristic (ROC) curve. The primary outcome was overall survival, which was estimated by the Kaplan-Meier method. The log-rank test was used to compare the differences in survival. Then, we conducted multivariate Cox analysis to assess the independent effect of the PLR on the survival of GBC patients. RESULTS: For the PLR, the area under the ROC curve was 0.620 (95%CI: 0.542-0.698, P = 0.040) in detecting death. The cut-off value for the PLR was determined to be 117.7, with 73.6% sensitivity and 53.2% specificity. The PLR was found to be significantly positively correlated with CA125 serum level, tumor-node-metastasis (TNM) stage, and tumor differentiation. Univariate analysis identified carcinoembryonic antigen (CEA), CA125 and CA199 levels, PLR, TNM stage, and the degree of differentiation as significant prognostic factors for GBC when they were expressed as binary data. Multivariate analysis showed that CA125 > 35 U/mL, CA199 > 39 U/mL, PLR ≥ 117.7, and TNM stage IV were independently associated with poor survival in GBC. When expressed as a continuous variable, the PLR was still an independent predictor for survival, with a hazard ratio of 1.018 (95%CI: 1.001-1.037 per 10-unit increase, P = 0.043). CONCLUSION: The PLR could be used as a simple, inexpensive, and valuable tool for predicting the prognosis of GBC patients.
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Plaquetas , Carcinoma/sangue , Neoplasias da Vesícula Biliar/sangue , Linfócitos , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Carcinoma/mortalidade , Carcinoma/patologia , Feminino , Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/patologia , Humanos , Estimativa de Kaplan-Meier , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Contagem de Plaquetas , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Curva ROC , Estudos RetrospectivosRESUMO
AIM: To investigate the prognostic value of preoperative platelet count (PLT) in patients with primary gallbladder cancer (GBC). METHODS: The clinical data of 223 GBC patients after surgery was retrospectively reviewed. A receiver operating characteristic (ROC) curve was plotted to verify the optimum cutoff point for PLT. Univariate and multivariate survival analyses were performed to identify the factors associated with the prognosis. RESULTS: The ROC curve showed that the optimum cutoff point for PLT was 178 × 10(9)/L, and the entire cohort was stratified into group A with PLT > 178 × 10(9)/L and group B with PLT ≤ 178 × 10(9)/L. Group A had a better survival than group B (P < 0.001). There was an obvious difference between the two groups in terms of the differentiation degree, advanced tumor stage, lymph node metastasis (P < 0.001) and pathological type (P < 0.05). The univariate analysis demonstrated that tumor location, differentiation degree, TNM stage, Nevin stage, lymph node metastasis and PLT were associated with overall survival (P < 0.001). In the multivariate analysis, PLT (P = 0.032), lymph node metastasis (P = 0.007), tumor location (P < 0.001) and TNM stage (P = 0.005) were independent prognostic factors. CONCLUSION: PLT is closely correlated with GBC prognosis and could be used to identify the population with a poorer prognosis after surgery.
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Plaquetas , Carcinoma/sangue , Neoplasias da Vesícula Biliar/sangue , Idoso , Área Sob a Curva , Carcinoma/mortalidade , Carcinoma/patologia , Carcinoma/cirurgia , Diferenciação Celular , Distribuição de Qui-Quadrado , Feminino , Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Contagem de Plaquetas , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
AIM: To investigate the prognostic significance of estrogen receptor 1 (ER1) and vascular endothelial growth factor A (VEGF-A) expression in primary gallbladder carcinoma (GBC) to identify new prognostic markers for this malignancy. METHODS: Using immunohistochemistry, we investigated ER1 and VEGF-A expression in 78 GBC and 78 cholelithiasis (CS) tissues. The results were correlated with clinicopathological features. Univariate and multivariate analyses were performed to evaluate the relationship between ER1 and VEGF-A expression and patients' prognosis. Further Kaplan-Meier survival analysis was also performed. RESULTS: ER1 and VEGF-A expression was significantly higher in GBC compared with CS (47/78 vs 28/78, P<0.05; 51/78 vs 33/78, P<0.05). ER1 expression was correlated with gender (P<0.05) and VEGF-A expression was correlated with tumor differentiation in GBC patients (P<0.05). In univariate analysis, age and tumor node metastasis (TNM) stage were factors associated with GBC prognosis (P<0.05). Although there was no statistical difference between the expression of ER1 or VEGF-A and overall survival, the high expression of ER1 combined with VEGF-A predicted a poor prognosis for GBC patients (16.30±1.87 vs 24.97±2.09, log-rank P<0.05). In multivariate analysis, combined expression of ER1 and VEGF-A and TNM stage were independent prognostic factors for GBC patients (P<0.05). CONCLUSION: Combined expression of ER1 and VEGF-A is a potential prognostic marker for GBC patients. Clinical detection of ER1 and VEGF-A in surgically resected GBC tissues would provide an important reference for decision-making of postoperative treatment programs.