RESUMO
BACKGROUND: Metastasis remains the main cause of cancer-related death for gastric cancer (GC) patients, but the mechanisms are poorly understood. Using The Cancer Genome Atlas (TCGA) data base and bioinformatics analyses, we identified C12orf59 might act as a potential oncogenic protein in GC. METHODS: We investigate the expression pattern and clinical significance of C12orf59 in two independent cohorts of GC samples. In the training cohort, we used the X-tile program software to generate the optimal cutoff value for C12orf59 expression in order to classify patients accurately according to clinical outcome. In the validation cohort, this derived cutoff score was applied to exam the association of C12orf59 expression with survival outcome. A series of in vivo and in vitro assays were then performed to investigate the function of C12orf59 in GC. RESULTS: C12orf59 was significantly upregulated, and associated with poor survival outcome in two cohorts of GC samples. Gain- and loss of- function studies demonstrated C12orf59 promotes GC cell invasive and metastatic capacity both in vitro and in vivo, and induces epithelial-mesenchymal transition and angiogenesis. Mechanically, C12orf59 exerts oncogenic functions by up-regulating CDH11 expression via NF-κB signaling. Interesting, CDH11 could in turn promote NF-κB bind to C12orf59's promoter and form a positive feedback loop to sustain the metastatic ability of GC cells. Additionally, downregulation of miR-654-5p is another important mechanism for C12orf59 overexpression in GC. CONCLUSION: Our finding suggested the newly identified C12orf59/NF-κB/CDH11 feedback loop may represent a new strategy for GC treatment.
Assuntos
Caderinas/metabolismo , Regulação Neoplásica da Expressão Gênica , NF-kappa B/metabolismo , Proteínas Oncogênicas/genética , Transdução de Sinais , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Adulto , Idoso , Biomarcadores Tumorais , Linhagem Celular Tumoral , Movimento Celular/genética , Transição Epitelial-Mesenquimal/genética , Feminino , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Estadiamento de Neoplasias , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Proteínas Oncogênicas/metabolismo , Prognóstico , Interferência de RNA , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologiaRESUMO
Dysregulation of non-coding RNAs, including miRNAs and lncRNAs has been reported to play vital roles in gastric cancer (GC) carcinogenesis, but the mechanism involved is largely unknown. Using the cancer genome atlas (TCGA) data set and bioinformatics analyses, we identified miR-532-5p as a potential tumor suppressor in GC, and found that lncRNA LINC01410 might be a negative regulator of miR-532-5p. We then conducted a series of in vivo and in vitro assays to explore the effect of LINC01410 on miR-532-5p-mediated GC malignancy and the underlying mechanism involved. MiR-532-5p overexpression inhibited GC metastasis and angiogenesis in vitro and in vivo, whereas miR-532-5p silencing had the opposite effect. Further study showed that miR-532-5p attenuated NF-κB signaling by directly inhibiting NCF2 expression, while miR-532-5p silencing in GC enhanced NF-κB activity. Furthermore, we demonstrated miR-532-5p down-regulation was caused by aberrantly high expression of LINC01410 in GC. Mechanistically, overexpression of LINC01410 promoted GC angiogenesis and metastasis by binding to and suppressing miR-532-5p, which resulted in up-regulation of NCF2 and sustained NF-κB pathway activation. Interestingly, NCF2 could in turn increase the promoter activity and expression of LINC01410 via NF-κB, thus forming a positive feedback loop that drives the malignant behavior of GC. Finally, high expression of LINC01410, along with low expression of miR-532-5p, was associated with poor survival outcome in GC patients. Our studies uncover a mechanism for constitutive LINC1410-miR-532-5p-NCF2-NF-κB feedback loop activation in GC, and consequently, as a potential therapeutic target in GC treatment.
Assuntos
Neoplasias Pulmonares/patologia , MicroRNAs/genética , NADPH Oxidases/genética , RNA Longo não Codificante/genética , Neoplasias Gástricas/patologia , Animais , Linhagem Celular Tumoral , Proliferação de Células , Bases de Dados Genéticas , Transição Epitelial-Mesenquimal , Retroalimentação Fisiológica , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Camundongos , NF-kappa B/metabolismo , Transplante de Neoplasias , Prognóstico , Regiões Promotoras Genéticas , Transdução de Sinais , Neoplasias Gástricas/genética , Análise de SobrevidaRESUMO
Solute carrier family 34 member 2 (SLC34A2), a pH-sensitive sodium-dependent phosphate transporter, is associated with several human cancers. In this study, we investigate the clinical significance of SLC34A2 and its function in human bladder cancer (BC). The expression dynamics of SLC34A2 were examined in two independent cohorts of BC samples by quantitative PCR, western blotting and immunohistochemical staining. In the training cohort (156 cases), we applied the X-tile program software to assess the optimal cutoff points for biomarkers in order to accurately classify patients according to clinical outcome. In the validation cohort (130 cases), the cutoff score derived from X-title analysis was investigated to determine the association of SLC34A2 expression with survival outcome. A series of in vitro and in vivo assays were then performed to elucidate the function of SLC34A2 in BC and its underlying mechanisms. Results showed that SLC34A2 was significantly upregulated in BC cell lines and clinical samples. In both two cohorts of BC samples, high expression of SLC34A2 was associated with large tumor size, advanced T status and poor patients' survival. The depletion of SLC34A2 in BC suppressed cellular viability, colony formation and anchorage-independent growth in vitro, and inhibited xenograft tumor growth in vivo, whereas overexpression of SLC34A2 had the converse effect. Simultaneously, downregulation of SLC34A2 decreased the transcriptional activity and protein expression level of c-Myc in BC cells, whereas restoration of c-Myc expression could compromise the anti-proliferation effect of SLC34A2 depletion. Furthermore, miR-214 was proved as a negative regulator of SLC34A2. Our present study illustrated that SLC34A2 has an important role in promoting proliferation and tumorigenicity of BC, and may represent a novel therapeutic target for this disease.
Assuntos
Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética , Proteínas Proto-Oncogênicas c-myb/genética , Proteínas Cotransportadoras de Sódio-Fosfato Tipo IIb/genética , Ativação Transcricional/genética , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/genética , Regulação para Baixo/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Transdução de Sinais/genética , Regulação para Cima/genéticaRESUMO
BACKGROUND: The development of chemoresistance and metastasis are the leading causes of death for gastric cancer (GC) patients, however, the molecular mechanisms involved remain unclear. Dysregulation of miRNAs is associated with a variety of disease, including GC. Recently, microarray profiling analysis revealed that miR-939 was dysregulated in human GC samples, but the role of miR-939 in GC has not been intensively investigated. METHODS: In the present study, we firstly examined the expression pattern of miR-939 in two independent cohorts of clinical GC samples: one cohort of 112 GC patients with stage I-III disease who underwent surgery followed by adjuvant chemotherapy; and another cohort of 110 GC patients with stage IV disease who received palliative chemotherapy. A series of in vivo and in vitro assays were then performed to investigate the function of miR-939 in GC. RESULTS: We detected that reduced expression of miR-939 was associated with chemoresistance and increased risk of tumor recurrence in GC patients. Further function study demonstrated that overexpression of miR-939 suppressed GC cell growth, and enhanced 5-fluorouracil-induced chemosensitivity by compromising cellular growth and inducing apoptosis in vitro and in vivo. Moreover, miR-939 repressed the migration and invasion of GC cells in vitro, and diminished the occurrence of lung metastasis in vivo. We further identified solute carrier family 34 member 2 (SLC34A2) was a novel target of miR-939. Mechanistically, we elucidated that miR-939 exerted its function mainly through inhibiting SLC34A2/Raf/MEK/ERK pathway, which is activated in GC. Multivariate analysis identified miR-939, SLC34A2, and their combination as independent indicators for poor prognosis and tumor recurrence in GC patients. CONCLUSION: Our data indicate that miR-939 acts as a tumor suppressor miRNA in GC, and miR-939/SLC34A2 axis represents a novel therapeutic strategy for future GC treatment.
Assuntos
Resistencia a Medicamentos Antineoplásicos/genética , Sistema de Sinalização das MAP Quinases , MicroRNAs/genética , Proteínas Cotransportadoras de Sódio-Fosfato Tipo IIb/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Quinases raf/metabolismo , Regiões 3' não Traduzidas , Animais , Linhagem Celular Tumoral , Proliferação de Células , Modelos Animais de Doenças , Regulação Neoplásica da Expressão Gênica , Xenoenxertos , Humanos , Estimativa de Kaplan-Meier , Camundongos , Metástase Neoplásica , Estadiamento de Neoplasias , Fosforilação , Interferência de RNA , Proteínas Cotransportadoras de Sódio-Fosfato Tipo IIb/metabolismo , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologiaRESUMO
PURPOSE: We previously reported the oncogenic role of paired-like homeodomain 2 (PITX2) in esophageal squamous cell carcinoma (ESCC). In this study, we aimed to identify the miRNA regulators of PITX2 and the mechanism underlying the pathogenesis of ESCC. EXPERIMENTAL DESIGN: Using miRNA profiling and bioinformatics analyses, we identified miR-644a as a negative mediator of PITX2 in ESCC. A series of in vivo and in vitro assays were performed to confirm the effect of miR-644a on PITX2-mediated ESCC malignancy. RESULTS: ESCC cells and tissues expressed less miR-644a than normal epithelial controls. In patient samples, lower expression of miR-644a in ESCC tissues was significantly correlated with tumor recurrence and/or metastasis, such that miR-644a, PITX2, and the combination of the two were independent prognostic indicators for ESCC patient's survival (P < 0.05). Gain- and loss-of-function studies demonstrated that miR-644a inhibited ESCC cell growth, migration, and invasion in vitro and suppressed tumor growth and metastasis in vivo In addition, miR-644a dramatically suppressed self-renewal and stem cell-like traits in ESCC cells. Furthermore, the effect of upregulation of miR-644a was similar to that of PITX2 knockdown in ESCC cells. Mechanistic studies revealed that miR-644a attenuates ESCC cells' malignancy and stem cell-associated phenotype, at least partially, by inactivation of the Akt/GSK-3ß/ß-catenin signaling pathway through PITX2. Furthermore, promoter hypermethylation caused downregulation of miR-644a in ESCC. CONCLUSIONS: Downregulation of miR-644a plays an important role in promoting both aggressiveness and stem-like traits of ESCC cells, suggesting that miR-644a may be useful as a novel prognostic biomarker or therapeutic target for the disease. Clin Cancer Res; 23(1); 298-310. ©2016 AACR.
Assuntos
Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/genética , MicroRNAs/genética , Células-Tronco Neoplásicas/metabolismo , Interferência de RNA , Fatores de Transcrição/genética , Animais , Biomarcadores Tumorais , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/mortalidade , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Metilação de DNA , Modelos Animais de Doenças , Progressão da Doença , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/mortalidade , Carcinoma de Células Escamosas do Esôfago , Perfilação da Expressão Gênica , Quinase 3 da Glicogênio Sintase/genética , Xenoenxertos , Humanos , Imunofenotipagem , Camundongos , Metástase Neoplásica , Fenótipo , Prognóstico , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas c-akt/metabolismo , Carga Tumoral/genética , Via de Sinalização Wnt , Proteína Homeobox PITX2RESUMO
Guanine nucleotide binding protein (G protein), alpha 13 (GNA13) has been implicated as an oncogenic protein in several human cancers. In this study, GNA13 was characterized for its role in gastric cancer (GC) progression and underlying molecular mechanisms. The expression dynamics of GNA13 were examined by immunohistochemistry (IHC) in two independent cohorts of GC samples. A series of in-vivo and in-vitro assays was performed to elucidate the function of GNA13 in GC and its underlying mechanisms. In both two cohorts of GC samples, we observed that GNA13 was markedly overexpressed in GC tissues and associated closely with aggressive magnitude of GC progression and poor patients' survival. Further study showed that upregulation of GNA13 expression increased the proliferation and tumorigenicity of GC cells in vitro and in vivo, by promoting cell growth rate, colony formation, and tumor formation in nude mice. By contrast, knockdown of GNA13 effectively suppressed the proliferation and tumorigenicity of GC cells in vitro and in vivo. Our results also demonstrated that the molecular mechanisms of the effect of GNA13 in GC included promotion of G1/S cell cycle transition through upregulation of c-Myc, activation of AKT and ERK activity, suppression of FOXO1 activity, upregulation of cyclin-dependent kinase (CDK) regulator cyclin D1 and downregulation of CDK inhibitor p21Cip1 and p27Kip1. Our present study illustrated that GNA13 has an important role in promoting proliferation and tumorigenicity of GC, and may represent a novel prognostic biomarker and therapeutic target for this disease.
Assuntos
Proliferação de Células , Subunidades alfa G12-G13 de Proteínas de Ligação ao GTP/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Gástricas/patologia , Animais , Apoptose , Western Blotting , Estudos de Casos e Controles , Ciclo Celular , Progressão da Doença , Feminino , Seguimentos , Subunidades alfa G12-G13 de Proteínas de Ligação ao GTP/genética , Humanos , Técnicas Imunoenzimáticas , Masculino , Camundongos , Camundongos SCID , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Taxa de Sobrevida , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
In this study, changes in eight GSTs mRNA level including GST-α, GST-σ, GST-ω, GST-π, GST-µ, GST-ρ, GST-θ and microsomal GST (mGST) in the oyster Crassostrea ariakensis after exposure to Prorocentrum lima have been evaluated by quantitative real-time PCR. Additionally, the contents of five GST isoforms were detected by ELISA. After exposure to P. lima at density of 2 × 10(5) cells/L, mGST mRNA significantly increased in gill, while GST-σ was induced in digestive gland. After exposure to P. lima at density of 2 × 10(6) cells/L, GST-ω and mGST expressions increased in gill, whereas GST-α and GST-σ were induced in digestive gland. The GST content and activity in oysters exposed to P. lima also showed a different pattern when the different isoforms and organs were compared. After exposure to P. lima (2 × 10(6) cell/L), GST-π increased in gill but decreased in digestive gland. The total GST enzyme activity increased in gill, while remained unchanged in digestive gland. These various regulation of GST gene expressions indicated that the GSTs isoenzymes might play divergent physiological roles in the detoxification of DSP toxins in C. ariakensis.
Assuntos
Crassostrea/efeitos dos fármacos , Dinoflagellida/química , Perfilação da Expressão Gênica , Glutationa Transferase/genética , Toxinas Marinhas/toxicidade , Animais , Crassostrea/genética , Ensaio de Imunoadsorção Enzimática , RNA Mensageiro/genéticaRESUMO
This meta-analysis sets out to systematically assess the efficacy of short course radiation (SRT) for rectal cancer patients based on randomized, controlled trials. Eight randomized controlled trials involving 6894 patients were ultimately included in this meta-analysis. Three trials (n = 2574) compared SRT with surgery alone. Local recurrence was improved (HR = 0.48, 95% CI 0.40 to 0.58). Overall survival was marginally improved with an HR of 0.90 (95% CI 0.81 to 1.00), but the magnitude of benefit was heterogeneous across trials. An additional three trials (n = 3682) compared SRT with selective postoperative radiation ± chemotherapy. A significant reduction of local recurrence (HR = 0.44, 95% CI 0.35 to 0.56) was also found after SRT. However, no benefit in overall survival was observed. Moreover, two trials (n = 638) compared SRT with long course chemoradiation. There was no statistically significant local recurrence or overall survival difference observed between the two strategies. Patients receiving SRT had lower grade 3 or 4 acute treatment related toxicity (RR 0.11, 95% CI 0.05 to 0.22) whereas no difference in late toxicity was observed. Overall, SRT is a reasonable alternative for resectable rectal cancer patients and should be part of an informed discussion of treatment options for this group of patients.
Assuntos
Neoplasias Retais/radioterapia , Humanos , Recidiva Local de Neoplasia/radioterapia , Radiação , PesquisaRESUMO
Herein, we determined the seroprevalence, seroconversion, and risk factors associated with Toxoplasma gondii (T. gondii) infection among pregnant women in Taipei, Taiwan. Pregnant women attending antenatal consultation in a Taipei medical center were invited, and 104 women completed a self-administered structured questionnaire. Venous blood samples were collected during the first and third trimester after consent was obtained. Serum IgG and IgM antibodies (Abs) as well as IgG avidity were analyzed using an enzyme-linked fluorescent assay. Of the samples collected in the first trimester, seven were seropositive for IgG Abs and one was seropositive for IgG + IgM Abs with a borderline avidity index, resulting in an overall seroprevalence of 7.7%. No statistically significant association was found between toxoplasmosis and age, pregnancy history, or any risk factors. Seroconversion was not detected from paired sera between the first and third trimesters. Pregnant women with senior high school education level or those who claimed to knowing Toxoplasma exhibited a significantly higher seroprevalence than those with bachelor degree (P = 0.05) or those who claimed not to have this knowledge (P = 0.05). Therefore, failure to understand the importance of T. gondii infection and the prevention measures resulted in the development of toxoplasmosis among these women.
Assuntos
Anticorpos Antiprotozoários/sangue , Complicações Infecciosas na Gravidez/epidemiologia , Toxoplasma/imunologia , Toxoplasmose/epidemiologia , Adulto , Afinidade de Anticorpos , Estudos Transversais , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Gravidez , Fatores de Risco , Soroconversão , Estudos Soroepidemiológicos , Inquéritos e Questionários , Taiwan/epidemiologia , Adulto JovemRESUMO
Plenty of studies have established that dysregulation of autophagy plays an essential role in cancer progression. The autophagy-related proteins have been reported to be closely associated with human cancer patients' prognosis. We explored the expression dynamics and prognostic value of autophagy-related protein ULK1 by immunochemistry (IHC) method in two independent cohorts of nasopharygeal carcinoma (NPC) cases. The X-tile program was applied to determine the optimal cut-off value in the training cohort. This derived cutoff value was then subjected to analysis the association of ULK1 expression with patients' clinical characteristics and survival outcome in the validation cohort and overall cases. High ULK1 expression was closely associated with aggressive clinical feature of NPC patients. Furthermore, high expression of ULK1 was observed more frequently in therapeutic resistant group than that in therapeutic effective group. Our univariate and multivariate analysis also showed that higher ULK1 expression predicted inferior disease-specific survival (DSS) (P<0.05). Consequently, a new clinicopathologic prognostic model with 3 poor prognostic factors (ie, ULK1 expression, overall clinical stage and therapeutic response) could significantly stratify risk (low, intermediate and high) for DSS in NPC patients (P<0.001). These findings provide evidence that, the examination of ULK1 expression by IHC method, could serve as an effective additional tool for predicting therapeutic response and patients' survival outcome in NPC patients.
Assuntos
Carcinoma/metabolismo , Carcinoma/mortalidade , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/mortalidade , Proteínas Serina-Treonina Quinases/metabolismo , Adulto , Idoso , Área Sob a Curva , Proteína Homóloga à Proteína-1 Relacionada à Autofagia , Biomarcadores , Carcinoma/terapia , Terapia Combinada , Feminino , Expressão Gênica , Humanos , Imuno-Histoquímica , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/terapia , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Proteínas Serina-Treonina Quinases/genética , Resultado do Tratamento , Regulação para CimaRESUMO
In the current study, we compared protein profiles in gills of Perna viridis after exposure to Prorocentrumlima, a dinoflagellate producing DSP toxins, and identified the differential abundances of protein spots using 2D-electrophoresis. After exposure to P. lima, the level of okadaic acid (a main component of DSP toxins) in gills of P. viridis significantly increased at 6 h, but mussels were all apparently healthy without death. Among the 28 identified protein spots by MALDI TOF/TOF-MS, 12 proteins were up-regulated and 16 were down-regulated in the P. lima-exposed mussels. These identified proteins were involved in various biological activities, such as metabolism, cytoskeleton, signal transduction, response to oxidative stress and detoxification. Taken together, our results indicated that the presence of P. lima caused DSP toxins accumulation in mussel gill, and might consequently induce cytoskeletonal disorganization,oxidative stress, a dysfunction in metabolism and ubiquitination/proteasome activity.
Assuntos
Dinoflagellida/fisiologia , Toxinas Marinhas/toxicidade , Perna (Organismo)/fisiologia , Proteoma/metabolismo , Poluentes da Água/toxicidade , Animais , Bivalves/metabolismo , Brânquias/metabolismo , Ácido Okadáico , Perna (Organismo)/metabolismo , ProteômicaRESUMO
PURPOSE: Bevacizumab has demonstrated survival benefit in patients with metastatic colorectal cancer (mCRC) when combined with chemotherapy. However, no validated predictors currently exist for its efficacy. Hypertension has been evaluated as a surrogate marker for efficacy of bevacizumab, although analyses, to date, have yielded conflicting results. The aim of this meta-analysis was to dissect the association between hypertension and efficacy of bevacizumab treatment in mCRC. METHODS: We searched PubMed, EMBASE, Chinese Biomedical Database (CBM), and Wan Fang Digital Journals before September, 2013. The primary clinical outcomes included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Relative risk (RR) or summary hazard ratio (HR) were calculated using a fixed-effects or random-effects model, depending on the heterogeneity of the included studies. Studies meeting our search criteria were assessed. RESULTS: Nine studies were considered eligible, with 1674 mCRC patients included. Six (308 patients, 104 with hypertension), 8 (1661 patients, 431 with hypertension) and 5 (1512 patients, 408 with hypertension) studies were eligible for the ORR, PFS and OS meta-analysis, respectively. Bevacizumab-related hypertension was associated with increased ORR (RR= 1.63; 95% CI 1.26-2.12; p=0.0002), improved PFS (HR=0.68; 95% CI 0.58-0.79; p<0.00001) and OS (HR=0.52; 95% CI 0.42-0.66; p<0.00001). There was no statistically significant difference between-study heterogeneity. CONCLUSION: These analyses suggest that hypertension may be a potential biomarker for efficacy of bevacizumab treatment in mCRC. Additional large prospective trials are required to confirm its predictive role.
Assuntos
Inibidores da Angiogênese/uso terapêutico , Bevacizumab/uso terapêutico , Biomarcadores , Neoplasias Colorretais/tratamento farmacológico , Hipertensão , Anticorpos Monoclonais Humanizados , Humanos , Estudos Prospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Several inflammation-based prognostic scoring systems, including Glasgow Prognostic Score (GPS), neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) have been reported to predict survival in many malignancies, whereas their role in metastatic nasopharyngeal carcinoma (NPC) remains unclear. The aim of this study is to evaluate the clinical value of these prognostic scoring systems in a cohort of cisplatin-based treated patients with metastatic NPC. METHODS: Two hundred and eleven patients with histologically proven metastatic NPC treated with first-line cisplatin-based chemotherapy were retrospectively evaluated. Demographics, disease-related characteristics and relevant laboratory data before treatment were recorded. GPS, NLR and PLR were calculated as described previously. Response to first-line therapy and survival data were also collected. Survival was analyzed in Cox regressions and stability of the models was examined by bootstrap resampling. The area under the receiver operating characteristics curve (AUC) was calculated to compare the discriminatory ability of each scoring system. RESULTS: Among the above three inflammation-based prognostic scoring systems, GPS (P<0.001) and NLR (Pâ=â0.019) were independently associated with overall survival, which showed to be stable in a bootstrap resampling study. The GPS consistently showed a higher AUC value at 6-month (0.805), 12-month (0.705), and 24-month (0.705) in comparison with NLR and PLR. Further analysis of the association of GPS with progression-free survival showed GPS was also associated independently with progression-free survival (P<0.001). CONCLUSIONS: Our study demonstrated that the GPS may be of prognostic value in metastatic NPC patients treated with cisplatin-based palliative chemotherapy and facilitate individualized treatment. However a prospective study to validate this prognostic model is still needed.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Ósseas/diagnóstico , Cisplatino/uso terapêutico , Neoplasias Hepáticas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Neoplasias Nasofaríngeas/diagnóstico , Adolescente , Adulto , Idoso , Área Sob a Curva , Plaquetas/patologia , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/secundário , Carcinoma , Contagem de Células , Feminino , Humanos , Inflamação/diagnóstico , Inflamação/tratamento farmacológico , Inflamação/mortalidade , Inflamação/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/secundário , Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Neutrófilos/patologia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Análise de SobrevidaRESUMO
The incidence of severe neonatal hyperbilirubinemia is higher in Asians than in whites. A case-control study was designed to investigate the effects of eight known risk factors [breast feeding, ABO incompatibility, premature birth, infection, cephalohematoma, asphyxia, glucose-6-phosphate dehydrogenase (G6PD) deficiency, and variant UDP-glucuronosyltransferase 1A1 (UGT1A1) gene] and a suspicious analog [organic anion transporter 2 (OATP 2) gene] on severe hyperbilirubinemia in Taiwanese neonates. The 72 study subjects and 100 hospital control subjects consisted of neonates with peak serum bilirubin levels > or =342 microM and <256.5 microM, respectively. The PCR-restriction fragment length polymorphism method was applied to detect the UGT1A1, OATP 2, and G6PD genes. The results of multivariate logistic regressions, adjusted for covariates, revealed odds ratios (ORs) of 4.64 [95% confidence interval (CI): 2.25-9.57; p < 0.001], 3.36 (95% CI: 1.54-7.35; p=0.002), and 3.02 (95% CI: 1.30-6.99; p=0.010) for neonates who were fed with breast milk, and carry the variant UGT1A1 gene at nucleotide 211 and the variant OATP 2 gene at nucleotide 388, respectively. The ORs, adjusted for covariates, for the other six risk factors were not statistically significant. The ORs in neonates who had one, two, and three significant risk factors were 8.46 (95% CI: 2.75-34.48; p < 0.001), 22.0 (95% CI: 5.50-88.0; p < 0.001), and 88.0 (95% CI: 12.50-642.50; p < 0.001), respectively. In conclusion, neonates who carry the 211 and 388 variants in the UGT1A1 and OATP 2 genes, respectively, as well as feed with breast milk are at high risk to develop severe hyperbilirubinemia.