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1.
Tumour Biol ; 42(5): 1010428320918404, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32364878

RESUMEN

Base excision repair, which is initiated by the DNA N-glycosylase proteins, is the frontline for repairing potentially mutagenic DNA base damage. Several base excision repair genes are deregulated in cancer and affect cellular outcomes to chemotherapy and carcinogenesis. Endonuclease VIII-like 3 (NEIL3) is a DNA glycosylase protein that is involved in oxidative and interstrand crosslink DNA damage repair. Our previous work has showed that NEIL3 is required to maintain replication fork integrity. It is unknown whether NEIL3 overexpression could contribute to cancer phenotypes, and its prognostic value and use as potential drug target remain unexplored. Our analysis of cancer genomics data sets reveals that NEIL3 frequently undergoes overexpression in several cancers. Furthermore, patients who exhibited NEIL3 overexpression with pancreatic adenocarcinoma, lung adenocarcinoma, lower grade glioma, kidney renal clear cell carcinoma, and kidney papillary cell carcinoma had worse overall survival. Importantly, NEIL3 overexpressed tumors accumulate mutation and chromosomal variations. Furthermore, NEIL3 overexpressed tumors exhibit simultaneous overexpression of homologous recombination genes (BRCA1/2) and mismatch repair genes (MSH2/MSH6). However, NEIL3 overexpression is negatively correlated with tumor overexpressing nucleotide excision repair genes (XPA, XPC, ERCC1/2). Our results suggest that NEIL3 might be a potential prognosis marker for high-risk patients, and/or an attractive therapeutic target for selected cancers.


Asunto(s)
Biomarcadores de Tumor , Expresión Génica , Variación Genética , N-Glicosil Hidrolasas/genética , Neoplasias/genética , Neoplasias/mortalidad , Línea Celular Tumoral , Variaciones en el Número de Copia de ADN , Daño del ADN , Reparación del ADN , Humanos , Estimación de Kaplan-Meier , Mutación , Neoplasias/diagnóstico , Pronóstico
2.
Medicine (Baltimore) ; 99(19): e20002, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32384455

RESUMEN

BACKGROUND: RNA-binding motif protein 3 (RBM3) plays an important role in carcinogenesis and tumor progression. However, the prognostic role of RBM3 in human carcinomas remains controversial. Therefore, we took a meta-analysis to research the association between the overall survival of patients with cancer and the expression of RBM3. METHODS: Systematic literature research identified 17 potentially eligible studies comprising 4976 patients in ten different cancer types. Two researchers independently screened the content and quality of studies and extracted data. Correlations of RBM3 expression and survival were analyzed and the hazard ratios (HRs) with 95% confidence intervals (95% CIs) were calculated. RESULTS: In the pooled analysis, overexpression of RBM3 was related to improved overall survival (OS), recurrence-free survival (RFS), and disease-free survival (DFS) in patients with cancer having a pooled HR of 0.61 (HR = 0.61; 95% CI: 0.47-0.69), 0.57 (HR = 0.60; 95% CI: 0.50-0.71) and 0.54 (HR 0.54; 95% CI: 0.38-0.78). Besides, subgroup analysis proved that overexpression of RBM3 was related to improved OS in colorectal cancer (HR = 0.61, 95% CI: 0.43-0.86), melanoma (HR = 0.32, 95% CI: 0.20-0.52), and gastric cancer (HR = 0.51, 95% CI: 0.35-0.73). However, subgroup analysis according to tumor type revealed that overexpression of RBM3 was not related to better OS in breast carcinoma (HR = 0.52, 95% CI: 0.17-0.61). CONCLUSIONS: Our results indicated that RBM3 overexpression was significantly predictive of better prognosis in various human cancers. For certain tumors, overexpression RBM3 might be a marker of improved survival in humans with cancer, except for breast cancer.


Asunto(s)
Expresión Génica , Neoplasias , Proteínas de Unión al ARN/genética , Humanos , Neoplasias/clasificación , Neoplasias/genética , Neoplasias/mortalidad , Pronóstico , Análisis de Supervivencia
3.
Medicine (Baltimore) ; 99(14): e19165, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32243358

RESUMEN

BACKGROUND: Previous studies have demonstrated that the C-reactive protein to albumin ratio (CAR) is correlated with the clinical outcomes of solid tumors. However, the available data have not been systematically evaluated. The objective of the present meta-analysis was to explore the prognostic value of the CAR in solid tumors. METHODS: Eligible studies were identified from the PubMed, EMBASE and Web of Science electronic databases. The clinical characteristics, disease -free survival (DFS) /progression-free survival (PFS) and overall survival (OS) were extracted from the eligible studies. The pooled hazard ratios (HRs) and 95% confidence intervals were calculated with STATA 12.0 software. We also performed subgroup, meta-regression and sensitivity analyses. RESULTS: In total, twenty-seven eligible studies including 10556 patients were enrolled in the present meta-analysis. The pooled HRs with 95% confidence intervals showed that the CAR was significantly associated with poor OS (HR = 1.95, 95% CI: 1.71-2.22) and DFS/PFS (HR = 1.82, 95% CI: 1.61-2.07) in patients with solid tumors. Although publication bias was found in the studies with regard to OS, a further trim and fill analysis revealed that the adjusted HR was 1.82 (95% CI: 1.69-1.96), which was close to the original HR. Subgroup analysis confirmed the CAR as a strong prognostic marker in patients with solid tumors, regardless of the tumor type, detection time, cut-off value, sample size and area. CONCLUSION: Our meta-analysis indicated that a high CAR might be an unfavorable prognostic marker for OS and DFS/PFS in patients with solid tumors.


Asunto(s)
Proteína C-Reactiva/análisis , Neoplasias/sangre , Neoplasias/mortalidad , Albúmina Sérica/análisis , Biomarcadores de Tumor , Supervivencia sin Enfermedad , Humanos , Pronóstico , Modelos de Riesgos Proporcionales
4.
Medicine (Baltimore) ; 99(15): e19698, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32282725

RESUMEN

BACKGROUND: Periodontal bacteria is the major pathogens in the oral cavity and the main cause of adult chronic periodontitis, but their association with incidence and prognosis in cancer is controversial. The aim of this study was to evaluate the effect of periodontal bacteria infection on incidence and prognosis of cancer. METHODS: A systematic literature search of PubMed, Embase, Web of Science, and Cochrane Library databases was performed to obtain 39 studies comprising 7184 participants. The incidence of cancer was evaluated as odd ratios (OR) with a 95% confidence interval (95% CI) using Review Manager 5.2 software. Overall survival, cancer-specific survival and disease-free survival, which were measured as hazard ratios (HR) with a 95% CI using Review Manager 5.2 software. RESULTS: Our results indicated that periodontal bacteria infection increased the incidence of cancer (OR = 1.25; 95%CI: 1.03-1.52) and was associated with poor overall survival (HR = 1.75; 95% CI: 1.40-2.20), disease-free survival (HR = 2.18; 95%CI: 1.24-3.84) and cancer-specific survival (HR = 1.85, 95%CI: 1.44-2.39). Subgroup analysis indicted that the risk of cancer was associated with Porphyromonas gingivalis (Pg) infection (OR = 2.16; 95%CI: 1.34-3.47) and Prevotella intermedia (Pi) infection (OR = 1.28; 95%CI: 1.01-1.63) but not Tannerella forsythia (Tf) (OR = 1.06; 95%CI: 0.8-1.41), Treponema denticola (Td) (OR = 1.30; 95%CI: 0.99-1.72), Aggregatibacter actinomycetemcomitans (Aa) (OR = 1.00; 95%CI: 0.48-2.08) and Fusobacterium nucleatum (Fn) (OR = 0.61; 95%CI: 0.32-1.16). CONCLUSION: This meta-analysis revealed periodontal bacteria infection increased the incidence of cancer and predicted poor prognosis of cancer.


Asunto(s)
Infecciones Bacterianas/microbiología , Periodontitis Crónica/microbiología , Boca/microbiología , Neoplasias/epidemiología , Aggregatibacter actinomycetemcomitans/aislamiento & purificación , Infecciones Bacterianas/complicaciones , Periodontitis Crónica/complicaciones , Supervivencia sin Enfermedad , Fusobacterium nucleatum/aislamiento & purificación , Humanos , Incidencia , Neoplasias/mortalidad , Porphyromonas gingivalis/aislamiento & purificación , Prevotella intermedia/aislamiento & purificación , Pronóstico , Medición de Riesgo , Treponema denticola/aislamiento & purificación
7.
Med Clin North Am ; 104(3): 391-403, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32312405

RESUMEN

Prognostication is a vital aspect of decision making because it provides patients and families with information to establish realistic and achievable goals of care, is used in determining eligibility for certain benefits, and helps in targeting interventions to those likely to benefit. Prognostication consists of 3 components: clinicians use their clinical judgment or other tools to estimate the probability of an individual developing a particular outcome over a specific period of time; this prognostic estimate is communicated in accordance with the patient's information preferences; the prognostic estimate is interpreted by the patient or surrogate and used in clinical decision making.


Asunto(s)
Competencia Clínica/normas , Enfermedad Crítica/terapia , Planificación de Atención al Paciente/normas , Atención Dirigida al Paciente/métodos , Anciano , Anciano de 80 o más Años , Toma de Decisiones Clínicas/ética , Comunicación , Enfermedad Crítica/epidemiología , Demencia/mortalidad , Demencia/terapia , Femenino , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/terapia , Humanos , Esperanza de Vida/tendencias , Masculino , Neoplasias/mortalidad , Neoplasias/terapia , Cuidados Paliativos/normas , Percepción , Pronóstico , Cuidado Terminal/normas
8.
JAMA ; 323(13): 1277-1285, 2020 04 07.
Artículo en Inglés | MEDLINE | ID: mdl-32259229

RESUMEN

Importance: Celiac disease may be associated with a modest but persistent increased long-term mortality risk. It is uncertain whether this risk has changed in the era of wider diagnosis rates, less severe clinical disease, and more widespread availability of gluten-free food. Objective: To evaluate the association between celiac disease and mortality risk in a population-based cohort in Sweden. Design, Setting, and Participants: All individuals in Sweden with celiac disease diagnosed between 1969 and 2017 were identified through the Epidemiology Strengthened by histoPathology Reports in Sweden (ESPRESSO) cohort. Participants (n = 49 829) were observed starting on the day of the biopsy. The final date of follow-up was December 31, 2017. Exposures: Celiac disease was defined by the presence of small intestinal villus atrophy on histopathology specimens during the years 1969-2017 from Sweden's 28 pathology departments. Each individual was matched with as many as 5 control participants in the general population by age, sex, county, and calendar period. Main Outcomes and Measures: The primary outcome was all-cause mortality, and the secondary outcome was cause-specific mortality. Patients with celiac disease were compared with controls using stratified Cox proportional modeling, stratifying by year of diagnosis. Results: There were 49 829 patients with celiac disease, including 24% who were diagnosed between the years 2010 and 2017. The mean (SD) age at diagnosis was 32.2 (25.2) years and 62.4% were women. During a median follow-up time of 12.5 years, 13.2% (n = 6596) died. Compared with controls (n = 246 426), overall mortality was increased in those with celiac disease (9.7 vs 8.6 deaths per 1000 person-years; absolute difference, 1.2 per 1000 person-years; hazard ratio [HR], 1.21 [95% CI, 1.17-1.25]). The relative increase in mortality risk was present in all age groups and was greatest in those diagnosed in the age range of 18 to 39 years (1.9 vs 1.1 per 1000 person-years; HR, 1.69 [95% CI, 1.47-1.94]; P values for heterogeneity comparing 18-39 years with 40-59 years and with ≥60 years were both <.001). Individuals with celiac disease were at increased risk of death from cardiovascular disease (3.5 vs 3.4 per 1000 person-years; HR, 1.08 [95% CI, 1.02-1.13]), cancer (2.7 vs 2.2 per 1000 person-years; HR, 1.29 [95% CI, 1.22-1.36]), and respiratory disease (0.6 vs 0.5 per 1000 person-years; HR, 1.21 [95% CI, 1.08-1.37]). When compared with controls, the overall mortality risk was greatest in the first year after diagnosis (15.3 vs 6.5 per 1000 person-years; HR, 2.34 [95% CI, 2.14-2.55]) but persisted beyond 10 years after diagnosis (10.5 vs 10.1 per 1000 person-years; HR, 1.15 [95% CI, 1.10-1.20]). The mortality risk was likewise present for patients diagnosed during the years 2010-2017 (7.5 vs 5.5 per 1000 person-years; HR, 1.35 [95% CI, 1.21-1.51]). Conclusions and Relevance: In a Swedish population studied between 1969 and 2017, a diagnosis of celiac disease compared with the general population was associated with a small but statistically significant increased mortality risk.


Asunto(s)
Enfermedad Celíaca/mortalidad , Adolescente , Adulto , Factores de Edad , Atrofia , Enfermedades Cardiovasculares/mortalidad , Estudios de Casos y Controles , Enfermedad Celíaca/complicaciones , Enfermedad Celíaca/patología , Niño , Escolaridad , Femenino , Humanos , Intestino Delgado/patología , Masculino , Persona de Mediana Edad , Neoplasias/mortalidad , Modelos de Riesgos Proporcionales , Enfermedades Respiratorias/mortalidad , Estudios Retrospectivos , Factores de Riesgo , Suecia/epidemiología , Adulto Joven
9.
Salud Publica Mex ; 62(2): 181-185, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32237560

RESUMEN

OBJECTIVE: To compare cancer mortality rates in Mexico from two national death registries that independently code and attribute cause of death. MATERIALS AND METHODS: We compared 5-year age-standardized total cancer and sitespecific cancer mortality rates (2010-2014) from Mexico's official death registry with a death registry from a disease surveillance system. We obtained age-adjusted mortality rates and 95% confidence intervals using the direct method and World Population Prospects 2010 as a standard. RESULTS: Cancer mortality estimates for Mexico were minimally affected by the use of two distinct death certificate-coding procedures. Cancer mortality was 73.3 for Instituto Nacional de Estadística y Geografía and 72.7 for System for Epidemiologic Death Statistics per 100 000 women. The corresponding estimates for men were 68.3 and 67.8. CONCLUSIONS: Mexico's low cancer mortality is unlikely to be explained by death certificate processing. Further investigations into the process of death certification and cancer registration should be conducted in Mexico.


Asunto(s)
Neoplasias/mortalidad , Femenino , Humanos , Masculino , México/epidemiología , Sistema de Registros
10.
Medicine (Baltimore) ; 99(14): e19596, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32243380

RESUMEN

This meta-analysis mainly summarized the studies reporting an association between statin use and cancer-specific mortality and recurrence or progression of cancer patients.We systematically searched for studies about the statin used in cancer patients in electronic databases, including PubMed, Web of Science, Cochrane, Clinical Trials, from inception through the November 2019. A total of 60 studies which included 953,177 participants were eligible with 233,322 cancer patients used statin. Our analysis selected studies presented with outcome based on hazard ratios (HRs) and 95% confidence intervals (CIs) of cancer-specific mortality and cancer recurrence-free survival or progression-free survival. Heterogeneity between the studies was examined using I statistics, and sensitivity analyses were conducted to assess the robustness of the findings. All statistical analyses were performed using RevMan software (version 5.3).The use of statin was potentially associated with a decline in cancer-specific mortality in cancer patients (HR = 0.78; 95% CI: 0.74, 0.84; n = 39; I = 85%). Furthermore, statin use was associated with improved recurrence-free survival (HR = 0.87; 95% CI: 0.78,0.97; n = 23; I = 64%), but not with improvement in progression-free survival (HR = 1.05; 95% CI: 0.95,1.16; n = 14; I2 = 38%).The meta-analysis demonstrated that statin use could exhibit potential survival benefit in the prognosis of cancer patients. But our results are conservative for statins to improve disease recurrence and progression. These findings should be assessed in a prospective randomized cohort.


Asunto(s)
Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Neoplasias/tratamiento farmacológico , Neoplasias/mortalidad , Femenino , Humanos , Masculino , Estudios Observacionales como Asunto , Pronóstico , Supervivencia sin Progresión , Modelos de Riesgos Proporcionales , Tasa de Supervivencia , Resultado del Tratamiento
11.
N Engl J Med ; 382(17): 1599-1607, 2020 04 23.
Artículo en Inglés | MEDLINE | ID: mdl-32223112

RESUMEN

BACKGROUND: Recent guidelines recommend consideration of the use of oral edoxaban or rivaroxaban for the treatment of venous thromboembolism in patients with cancer. However, the benefit of these oral agents is limited by the increased risk of bleeding associated with their use. METHODS: This was a multinational, randomized, investigator-initiated, open-label, noninferiority trial with blinded central outcome adjudication. We randomly assigned consecutive patients with cancer who had symptomatic or incidental acute proximal deep-vein thrombosis or pulmonary embolism to receive oral apixaban (at a dose of 10 mg twice daily for the first 7 days, followed by 5 mg twice daily) or subcutaneous dalteparin (at a dose of 200 IU per kilogram of body weight once daily for the first month, followed by 150 IU per kilogram once daily). The treatments were administered for 6 months. The primary outcome was objectively confirmed recurrent venous thromboembolism during the trial period. The principal safety outcome was major bleeding. RESULTS: Recurrent venous thromboembolism occurred in 32 of 576 patients (5.6%) in the apixaban group and in 46 of 579 patients (7.9%) in the dalteparin group (hazard ratio, 0.63; 95% confidence interval [CI], 0.37 to 1.07; P<0.001 for noninferiority). Major bleeding occurred in 22 patients (3.8%) in the apixaban group and in 23 patients (4.0%) in the dalteparin group (hazard ratio, 0.82; 95% CI, 0.40 to 1.69; P = 0.60). CONCLUSIONS: Oral apixaban was noninferior to subcutaneous dalteparin for the treatment of cancer-associated venous thromboembolism without an increased risk of major bleeding. (Funded by the Bristol-Myers Squibb-Pfizer Alliance; Caravaggio ClinicalTrials.gov number, NCT03045406.).


Asunto(s)
Anticoagulantes/administración & dosificación , Dalteparina/administración & dosificación , Hemorragia/inducido químicamente , Neoplasias/complicaciones , Pirazoles/administración & dosificación , Piridonas/administración & dosificación , Prevención Secundaria/métodos , Tromboembolia Venosa/prevención & control , Administración Oral , Anciano , Anticoagulantes/efectos adversos , Dalteparina/efectos adversos , Femenino , Hemorragia/epidemiología , Humanos , Incidencia , Inyecciones Subcutáneas , Análisis de Intención de Tratar , Masculino , Persona de Mediana Edad , Neoplasias/mortalidad , Modelos de Riesgos Proporcionales , Embolia Pulmonar/prevención & control , Pirazoles/efectos adversos , Piridonas/efectos adversos , Método Simple Ciego , Tromboembolia Venosa/tratamiento farmacológico , Tromboembolia Venosa/etiología , Trombosis de la Vena/prevención & control
12.
Crit Rev Oncol Hematol ; 149: 102909, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32146284

RESUMEN

OBJECTIVE: This meta-analysis was to evaluate the impact of antibiotics use on survival of cancer patients with immune checkpoint inhibitors (ICIs). METHODS: Electronic databases including Pubmed, Emabse, and the Cochrane library were searched. The primary endpoints were overall survival (OS) and progression-free survival (PFS). RESULTS: A total of 20 retrospective studies were included. The median OS (7.9 months versus 17.65 months) and PFS (2.4 months versus 4.4 months) of the antibiotics use group were shorter compared to control group. Meta-analysis also showed that the risks of death (HR = 1.90, 95 % CI: 1.55-2.34; P < 0.01) and disease progression (HR=1.53, 95 % CI: 1.30-1.79; P < 0.01) in antibiotics positive group were significantly higher than that of the negative group. The prognostic role of antibiotics use was still significant regardless of cancer types and timing of antibiotics (P < 0.01 for all). CONCLUSION: Use of antibiotics may be associated with worse outcomes in cancer patients treated with ICIs.


Asunto(s)
Antibacterianos/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Progresión de la Enfermedad , Humanos , Neoplasias/mortalidad , Neoplasias/patología , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del Tratamiento
13.
Medicine (Baltimore) ; 99(9): e19306, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32118751

RESUMEN

The study aimed to explore whether cancer-related pain and opioids use are associated with the survival of cancer patients, and perform a cohort study and a meta-analysis to quantify the magnitude of any association.A retrospective cohort study was performed to analyze the impact of pain level, and opioids use on cancer-specific survival (CSS) in advanced cancer patients. Patients and relevant medical records were selected from the registry of the Radiation and chemotherapy division of Ningbo First Hospital between June 2013 and October 2017. Hazard ratios (HRs) and 95% confidential intervals (CIs) for CSS by opioids use were calculated by univariate and multivariate Cox regression analyses. The systematic review included relevant studies published before October 2018. The combined HRs and 95% CIs for overall survival (OS) and progression-free survival (PFS) were calculated using random-effect models.A total of consecutive 203 cancer patients were included in the cohort study. Kaplan-Meier curves indicate a negative association between CSS and cancer-related pain or opioids requirement, but less evidence of an association with the dose of opioids use. Multivariate models revealed that the pain level and opioids requirement were associated with shorter CSS, after adjusting for significant covariates. The results of the meta-analysis indicated that postoperative opioids use had a poor effect on PFS, and opioids use for cancer-related pain was associated with poor OS in cancer patients, while intraoperative opioids use was not associated with cancer survival.We concluded that cancer-related pain and opioids requirements are associated with poor survival in advanced cancer patients, and postoperative opioids use and opioids use for cancer-related pain may have an adverse effect on the survival of cancer patients.


Asunto(s)
Analgésicos Opioides/normas , Neoplasias/tratamiento farmacológico , Neoplasias/mortalidad , Dolor/tratamiento farmacológico , Adulto , Anciano , Analgésicos Opioides/uso terapéutico , Análisis de Varianza , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/complicaciones , Dolor/etiología , Manejo del Dolor/métodos , Manejo del Dolor/normas , Manejo del Dolor/estadística & datos numéricos , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Análisis de Supervivencia
14.
Medicine (Baltimore) ; 99(13): e19604, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32221082

RESUMEN

BACKGROUND: Many studies have been done to reported the value of SRY-related HMG-box Gene 2 (SOX2) in prognosis of solid tumors. But results were not particularly consistent among these studies because of the limitations of the small sample data. METHODS: We searched relevant studies published before November 2018 by PubMed, Web of Science and EMBASE. In this meta-analysis, hazard ratio (HR) values for overall survival (OS) were cumulatively pooled and quantitatively analyzed. RESULTS: A meta-analysis based on 12 studies with 3318 patients was conducted to assess the potential correlation between SOX2 overexpression and OS in human solid tumors. A total of 12 studies (n = 3318) were assessed in the meta-analysis. It suggested that the high expression of SOX2 obviously indicates poor survival and prognosis in both univariate and multivariate analysis. In the univariate analysis, the combined HR for OS was 1.66 (95% confidence interval [CI]: 1.46-1.89, P < .001). The pooled HR of multivariate analysis for OS was 1.51 (95% confidence interval [CI]: 1.32-1.71, P < .001). CONCLUSIONS: This meta-analysis indicated that the high expression level of SOX2 is significantly associated with a decline in survival of human with solid tumors. On the basis of the expression level in solid tumors, SOX2 is expected to be a meaningful prognostic biomarker and effective therapeutic target.


Asunto(s)
Neoplasias/genética , Neoplasias/mortalidad , Factores de Transcripción SOXB1/biosíntesis , Biomarcadores de Tumor , Regulación Neoplásica de la Expresión Génica , Humanos , Pronóstico , Modelos de Riesgos Proporcionales , Análisis de Supervivencia
15.
JAMA ; 323(12): 1151-1160, 2020 03 24.
Artículo en Inglés | MEDLINE | ID: mdl-32207799

RESUMEN

Importance: It is unclear whether the number of steps per day and the intensity of stepping are associated with lower mortality. Objective: Describe the dose-response relationship between step count and intensity and mortality. Design, Setting, and Participants: Representative sample of US adults aged at least 40 years in the National Health and Nutrition Examination Survey who wore an accelerometer for up to 7 days ( from 2003-2006). Mortality was ascertained through December 2015. Exposures: Accelerometer-measured number of steps per day and 3 step intensity measures (extended bout cadence, peak 30-minute cadence, and peak 1-minute cadence [steps/min]). Accelerometer data were based on measurements obtained during a 7-day period at baseline. Main Outcomes and Measures: The primary outcome was all-cause mortality. Secondary outcomes were cardiovascular disease (CVD) and cancer mortality. Hazard ratios (HRs), mortality rates, and 95% CIs were estimated using cubic splines and quartile classifications adjusting for age; sex; race/ethnicity; education; diet; smoking status; body mass index; self-reported health; mobility limitations; and diagnoses of diabetes, stroke, heart disease, heart failure, cancer, chronic bronchitis, and emphysema. Results: A total of 4840 participants (mean age, 56.8 years; 2435 [54%] women; 1732 [36%] individuals with obesity) wore accelerometers for a mean of 5.7 days for a mean of 14.4 hours per day. The mean number of steps per day was 9124. There were 1165 deaths over a mean 10.1 years of follow-up, including 406 CVD and 283 cancer deaths. The unadjusted incidence density for all-cause mortality was 76.7 per 1000 person-years (419 deaths) for the 655 individuals who took less than 4000 steps per day; 21.4 per 1000 person-years (488 deaths) for the 1727 individuals who took 4000 to 7999 steps per day; 6.9 per 1000 person-years (176 deaths) for the 1539 individuals who took 8000 to 11 999 steps per day; and 4.8 per 1000 person-years (82 deaths) for the 919 individuals who took at least 12 000 steps per day. Compared with taking 4000 steps per day, taking 8000 steps per day was associated with significantly lower all-cause mortality (HR, 0.49 [95% CI, 0.44-0.55]), as was taking 12 000 steps per day (HR, 0.35 [95% CI, 0.28-0.45]). Unadjusted incidence density for all-cause mortality by peak 30 cadence was 32.9 per 1000 person-years (406 deaths) for the 1080 individuals who took 18.5 to 56.0 steps per minute; 12.6 per 1000 person-years (207 deaths) for the 1153 individuals who took 56.1 to 69.2 steps per minute; 6.8 per 1000 person-years (124 deaths) for the 1074 individuals who took 69.3 to 82.8 steps per minute; and 5.3 per 1000 person-years (108 deaths) for the 1037 individuals who took 82.9 to 149.5 steps per minute. Greater step intensity was not significantly associated with lower mortality after adjustment for total steps per day (eg, highest vs lowest quartile of peak 30 cadence: HR, 0.90 [95% CI, 0.65-1.27]; P value for trend = .34). Conclusions and Relevance: Based on a representative sample of US adults, a greater number of daily steps was significantly associated with lower all-cause mortality. There was no significant association between step intensity and mortality after adjusting for total steps per day.


Asunto(s)
Enfermedades Cardiovasculares/mortalidad , Marcha/fisiología , Neoplasias/mortalidad , Caminata/fisiología , Acelerometría , Adulto , Anciano , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Encuestas Nutricionales , Modelos de Riesgos Proporcionales , Estados Unidos/epidemiología
16.
BMC Bioinformatics ; 21(1): 76, 2020 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-32111152

RESUMEN

BACKGROUND: Cancer prognosis prediction is valuable for patients and clinicians because it allows them to appropriately manage care. A promising direction for improving the performance and interpretation of expression-based predictive models involves the aggregation of gene-level data into biological pathways. While many studies have used pathway-level predictors for cancer survival analysis, a comprehensive comparison of pathway-level and gene-level prognostic models has not been performed. To address this gap, we characterized the performance of penalized Cox proportional hazard models built using either pathway- or gene-level predictors for the cancers profiled in The Cancer Genome Atlas (TCGA) and pathways from the Molecular Signatures Database (MSigDB). RESULTS: When analyzing TCGA data, we found that pathway-level models are more parsimonious, more robust, more computationally efficient and easier to interpret than gene-level models with similar predictive performance. For example, both pathway-level and gene-level models have an average Cox concordance index of ~ 0.85 for the TCGA glioma cohort, however, the gene-level model has twice as many predictors on average, the predictor composition is less stable across cross-validation folds and estimation takes 40 times as long as compared to the pathway-level model. When the complex correlation structure of the data is broken by permutation, the pathway-level model has greater predictive performance while still retaining superior interpretative power, robustness, parsimony and computational efficiency relative to the gene-level models. For example, the average concordance index of the pathway-level model increases to 0.88 while the gene-level model falls to 0.56 for the TCGA glioma cohort using survival times simulated from uncorrelated gene expression data. CONCLUSION: The results of this study show that when the correlations among gene expression values are low, pathway-level analyses can yield better predictive performance, greater interpretative power, more robust models and less computational cost relative to a gene-level model. When correlations among genes are high, a pathway-level analysis provides equivalent predictive power compared to a gene-level analysis while retaining the advantages of interpretability, robustness and computational efficiency.


Asunto(s)
Neoplasias/mortalidad , Estudios de Cohortes , Expresión Génica , Glioma/genética , Glioma/mortalidad , Humanos , Modelos Genéticos , Neoplasias/genética , Pronóstico , Modelos de Riesgos Proporcionales
17.
Bull Cancer ; 107(4): 410-416, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32145962

RESUMEN

Tumor profiling has been shown to benefit patients with rare or refractory metastatic cancer, but several limitations hamper its use in daily clinical practice. We aim to assess the added benefit of a comprehensive tumor profiling, including factors predictive of response to targeted and cytotoxic therapy, in the treatment of refractory or rare solid tumors outside of a formal clinical trial. Patients were included between 2013 and 2017. Multiplatform comprehensive tumor profiling (CTP) was performed on FFPE specimens. Tumor response was evaluated by imaging using the RECIST criteria version 1.1. The PFS ratio was defined as PFS under CTP-guided therapy (PFS2)/PFS under previous standard therapy (PFS1). A clinical benefit was identified if the PFS ratio exceeded the 1.3 threshold value. In total, 184 patients were enrolled among whom 104 were evaluable for the PFS ratio. Objective response rates (ORR) were equal to 25% (CI95: 16.6-33.4%) and 36.5% (CI95: 27.2-45.8%) on the last therapy before CTP and on the CTP-guided therapy respectively (P-value=0.058 on paired proportion comparison test). The proportion of patients achieving a PFS2/PFS1 ratio≥1.3 was equal to 50%. The median PFS1 was statistically lower than PFS2 (120 days compared to 184 days respectively, P-value log rank 0.01). These results confirm the feasibility and the added benefit of a CTP in patients with refractory tumors in daily clinical practice especially in patients not able to enter a clinical trial.


Asunto(s)
Antineoplásicos/uso terapéutico , Terapia Molecular Dirigida/métodos , Proteínas de Neoplasias/genética , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Enfermedades Raras/tratamiento farmacológico , Enfermedades Raras/genética , Adulto , Anciano , Anciano de 80 o más Años , Algoritmos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/antagonistas & inhibidores , Toma de Decisiones Clínicas , Estudios de Factibilidad , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Inmunohistoquímica , Hibridación in Situ/métodos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Mutación , Proteínas de Neoplasias/análisis , Proteínas de Neoplasias/antagonistas & inhibidores , Neoplasias/mortalidad , Probabilidad , Supervivencia sin Progresión , Análisis por Matrices de Proteínas/métodos , Enfermedades Raras/mortalidad , Criterios de Evaluación de Respuesta en Tumores Sólidos , Tasa de Supervivencia , Adulto Joven
18.
Lancet ; 395(10226): 785-794, Mar., 2020. graf., tab.
Artículo en Inglés | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1095826

RESUMEN

BACKGROUND: To our knowledge, no previous study has prospectively documented the incidence of common diseases and related mortality in high-income countries (HICs), middle-income countries (MICs), and low-income countries (LICs) with standardised approaches. Such information is key to developing global and context-specific health strategies. In our analysis of the Prospective Urban Rural Epidemiology (PURE) study, we aimed to evaluate differences in the incidence of common diseases, related hospital admissions, and related mortality in a large contemporary cohort of adults from 21 HICs, MICs, and LICs across five continents by use of standardised approaches. METHODS: The PURE study is a prospective, population-based cohort study of individuals aged 35-70 years who have been enrolled from 21 countries across five continents. The key outcomes were the incidence of fatal and non-fatal cardiovascular diseases, cancers, injuries, respiratory diseases, and hospital admissions, and we calculated the age-standardised and sex-standardised incidence of these events per 1000 person-years. FINDINGS: This analysis assesses the incidence of events in 162 534 participants who were enrolled in the first two phases of the PURE core study, between Jan 6, 2005, and Dec 4, 2016, and who were assessed for a median of 9·5 years (IQR 8·5-10·9). During follow-up, 11 307 (7·0%) participants died, 9329 (5·7%) participants had cardiovascular disease, 5151 (3·2%) participants had a cancer, 4386 (2·7%) participants had injuries requiring hospital admission, 2911 (1·8%) participants had pneumonia, and 1830 (1·1%) participants had chronic obstructive pulmonary disease (COPD). Cardiovascular disease occurred more often in LICs (7·1 cases per 1000 person-years) and in MICs (6·8 cases per 1000 person-years) than in HICs (4·3 cases per 1000 person-years). However, incident cancers, injuries, COPD, and pneumonia were most common in HICs and least common in LICs. Overall mortality rates in LICs (13·3 deaths per 1000 person-years) were double those in MICs (6·9 deaths per 1000 person-years) and four times higher than in HICs (3·4 deaths per 1000 person-years). This pattern of the highest mortality in LICs and the lowest in HICs was observed for all causes of death except cancer, where mortality was similar across country income levels. Cardiovascular disease was the most common cause of deaths overall (40%) but accounted for only 23% of deaths in HICs (vs 41% in MICs and 43% in LICs), despite more cardiovascular disease risk factors (as judged by INTERHEART risk scores) in HICs and the fewest such risk factors in LICs. The ratio of deaths from cardiovascular disease to those from cancer was 0·4 in HICs, 1·3 in MICs, and 3·0 in LICs, and four upper-MICs (Argentina, Chile, Turkey, and Poland) showed ratios similar to the HICs. Rates of first hospital admission and cardiovascular disease medication use were lowest in LICs and highest in HICs. INTERPRETATION: Among adults aged 35-70 years, cardiovascular disease is the major cause of mortality globally. However, in HICs and some upper-MICs, deaths from cancer are now more common than those from cardiovascular disease, indicating a transition in the predominant causes of deaths in middle-age. As cardiovascular disease decreases in many countries, mortality from cancer will probably become the leading cause of death. The high mortality in poorer countries is not related to risk factors, but it might be related to poorer access to health care. (AU)


Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Enfermedades Cardiovasculares , Neoplasias/mortalidad
19.
Biosci Trends ; 14(1): 42-47, 2020 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-32023575

RESUMEN

Posttransplant malignancy has become a significant cause of mortality. Data on the long-term outcomes of patients with pretransplant nonhepatic malignancy (PTM) after living donor liver transplantation (LDLT) are scarce, although the recipients of other organs with PTM have been reported to have a poor survival. Fifteen patients with PTM (4.4%) among the 342 adult recipients were identified in our LDLT programs. The outcomes of the patients with PTM after LDLT were compared to those of patients without PTM in terms of the all-cause mortality and cancer-specific mortality (defined as mortality related to malignancy expect for hepatocellular carcinoma, cholangiocarcinoma, or neuroendocrine tumor). The sites of PTM included the breast in six, stomach in two, and colon, lung, kidney, uterine, thyroid, larynx, and acute myelogenous leukemia in one each. The median interval from the PTM treatment to LDLT was 57 months (range, 2-298). The patients who received the curative treatment for PTM were selected as the recipients. No patients with PTM had recurrence during the follow-up period. The 1-, 5-, and 10-year patient survival rates were 100%, 92.9%, and 92.9% in the PTM group and 86.2%, 76.7%, and 68.5% in the non-PTM group, respectively (p = 0.142). Likewise, there was no significant difference between the two groups in the cancer-specific mortality. In conclusion, the patients with PTM had comparable outcomes with regard to mortality and cancer-specific mortality compared with those without PTM. This study showed that the patients with PTM can obtain an acceptable outcome after LDLT when carefully selected.


Asunto(s)
Trasplante de Hígado , Neoplasias/mortalidad , Anciano , Femenino , Humanos , Donadores Vivos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Medición de Riesgo , Tasa de Supervivencia
20.
Nucleic Acids Res ; 48(5): 2287-2302, 2020 03 18.
Artículo en Inglés | MEDLINE | ID: mdl-32002550

RESUMEN

Accumulating evidence has demonstrated that transcriptional regulation is affected by DNA methylation. Understanding the perturbation of DNA methylation-mediated regulation between transcriptional factors (TFs) and targets is crucial for human diseases. However, the global landscape of DNA methylation-mediated transcriptional dysregulation (DMTD) across cancers has not been portrayed. Here, we systematically identified DMTD by integrative analysis of transcriptome, methylome and regulatome across 22 human cancer types. Our results revealed that transcriptional regulation was affected by DNA methylation, involving hundreds of methylation-sensitive TFs (MethTFs). In addition, pan-cancer MethTFs, the regulatory activity of which is generally affected by DNA methylation across cancers, exhibit dominant functional characteristics and regulate several cancer hallmarks. Moreover, pan-cancer MethTFs were found to be affected by DNA methylation in a complex pattern. Finally, we investigated the cooperation among MethTFs and identified a network module that consisted of 43 MethTFs with prognostic potential. In summary, we systematically dissected the transcriptional dysregulation mediated by DNA methylation across cancer types, and our results provide a valuable resource for both epigenetic and transcriptional regulation communities.


Asunto(s)
Biomarcadores de Tumor/genética , ADN de Neoplasias/genética , Epigénesis Genética , Regulación Neoplásica de la Expresión Génica , Neoplasias/genética , Factores de Transcripción/genética , Biomarcadores de Tumor/metabolismo , Islas de CpG , Metilación de ADN , ADN de Neoplasias/metabolismo , Femenino , Redes Reguladoras de Genes , Genoma Humano , Humanos , Masculino , Anotación de Secuencia Molecular , Neoplasias/metabolismo , Neoplasias/mortalidad , Neoplasias/patología , Análisis de Supervivencia , Factores de Transcripción/clasificación , Factores de Transcripción/metabolismo , Transcriptoma
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