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1.
Gut ; 69(1): 103-111, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31023832

RESUMO

OBJECTIVE: We assessed the effect of surgical resection of colorectal cancer (CRC) on perioperative plasma vitamin D (25OHD) and C-reactive protein (CRP) level. We investigated the relationship between circulating vitamin D level and CRC survival. DESIGN: We sequentially sampled 92 patients undergoing CRC resection, and measured plasma 25OHD and CRP. For survival analyses, we assayed 25OHD and CRP in two temporally distinct CRC patient cohorts (n=2006, n=2100) and investigated the association between survival outcome, circulating vitamin D and systemic inflammatory response. RESULTS: Serial sampling revealed a postoperative fall (mean 17.3 nmol/L; p=3.6e-9) in plasma 25OHD (nadir days 1-2). CRP peaked 3-5 days postoperatively (143.1 mg/L; p=1.4e-12), yet the postoperative fall in 25OHD was independent of CRP. In cohort analyses, 25OHD was lower in the 12 months following operation (mean=48.8 nmol/L) than preoperatively (54.8 nmol/L; p=1.2e-5) recovering after 24 months (52.2 nmol/L; p=0.002). Survival analysis in American Joint Committee on Cancer stages I-III demonstrated associations between 25OHD tertile and CRC mortality (HR=0.69; 95% CI 0.46 to 0.91) and all-cause mortality (HR=0.68; 95% CI 0.50 to 0.85), and was independent of CRP. We observed interaction effects between plasma 25OHD and rs11568820 genotype (functional VDR polymorphism) with a strong protective effect of higher 25OHD only in patients with GG genotype (HR=0.51; 95% CI 0.21 to 0.81). We developed an online tool for predicted survival (https://apps.igmm.ed.ac.uk/mortalityCalculator/) that incorporates 25OHD with clinically useful predictive performance (area under the curve 0.77). CONCLUSIONS: CRC surgery induces a fall in circulating 25OHD. Plasma 25OHD level is a prognostic biomarker with low 25OHD associated with poorer survival, particularly in those with rs11568820 GG genotype. A randomised trial of vitamin D supplementation after CRC surgery has compelling rationale.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Colorretais/cirurgia , Vitamina D/análogos & derivados , Idoso , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Neoplasias Colorretais/sangue , Neoplasias Colorretais/genética , Feminino , Seguimentos , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Prognóstico , Receptores de Calcitriol/genética , Análise de Sobrevida , Síndrome de Resposta Inflamatória Sistêmica/sangue , Vitamina D/sangue
2.
Arq Gastroenterol ; 56(4): 399-404, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31800736

RESUMO

BACKGROUND: Colorectal cancer (CRC) is one of the leading causes of cancer worldwide. Early diagnostic methods using serum biomarkers are required. The study of omics, most recently lipidomics, has the purpose of analyzing lipids for a better understanding of human lipidoma. The evolution of mass spectrometry methods, such as MALDI-MS technology, has enabled the detection and identification of a wide variety of lipids with great potential to open new avenues for predictive and preventive medicine. OBJECTIVE: To determine the lipid profile of patients with colorectal cancer and polyps. METHODS: Patients with stage I-III CRC, adenomatous polyps and individuals with normal colonoscopy were selected. All patients underwent peripheral blood collection for lipid extraction. The samples were analyzed by MALDI-MS technique for lipid identification. STATISTICAL ANALYSIS: Univariate and multivariate (principal component analysis [PCA] and discriminant analysis by partial least squares [PLS-DA]) analyses workflows were applied to the dataset, using MetaboAnalyst 3.0 software. The ions were identified according to the class of lipids using the online database Lipid Maps (http://www.lipidmaps.org). RESULTS: We included 88 individuals, 40 with CRC, 12 with polyps and 32 controls. Boxplot analysis showed eight VIP ions in the three groups. Differences were observed between the cancer and control groups, as well as between cancer and polyp, but not between polyps and control. The polyketide (810.1) was the lipid represented in cancer and overrepresented in polyp and control. Among the patients with CRC we observed differences between lipids with lymph node invasion (N1-2) compared to those without lymph node invasion (N). CONCLUSION: Possible lipid biomarkers were identified among cancer patients compared to control and polyp groups. The polyketide lipid (810.1) was the best biomarker to differentiate the cancer group from control and polyp. We found no difference between the biomarkers in the polyp group in relation to the control.


Assuntos
Pólipos do Colo/diagnóstico , Neoplasias Colorretais/diagnóstico , Lipídeos/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Estudos de Casos e Controles , Pólipos do Colo/sangue , Colonoscopia , Neoplasias Colorretais/sangue , Detecção Precoce de Câncer , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias
3.
Medicine (Baltimore) ; 98(44): e17696, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689796

RESUMO

Liver resection (LR) is the standard procedure for treating colorectal cancer (CRC) hepatic metastasis; however, LR associated with a high recurrence incidence. This study aimed to determine an optimal post-LR adjuvant chemotherapeutic strategy to improve overall long-term patient outcomes. A retrospective study of 490 patients who had undergone curative LR for CRC hepatic metastasis was performed. Patients who underwent post-LR adjuvant chemotherapy demonstrated high overall survival (OS) rates (hazard ratio [HR] = 0.58, P = .002) but not high recurrence-free survival (RFS) rates (HR = 1.02, P = .885). Moreover, OS was significantly longer in patients who underwent 5-fluorouracil + leucovorin (5-FU/LV; HR = 0.63, P = .039), oxaliplatin-based chemotherapy (HR = 0.45, P < .001), or irinotecan-based chemotherapy with bevacizumab (HR = 0.64, P = .040) than in those who did not. Among patients with carcinoembryonic antigen (CEA) levels of <5 ng/mL at 1 month after LR, significant differences were noted only in those who underwent 5-FU/LV (HR = 0.58, P = .035) and oxaliplatin-based chemotherapy (HR = 0.38, P < .001). In conclusion, perioperative CEA levels are crucial in prognosis and treatment of patients with CRC hepatic metastasis after LR. Additionally, certain regimens of adjuvant chemotherapy alongside post-LR CEA levels may provide beneficial results.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno Carcinoembrionário/sangue , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimioterapia Adjuvante , Neoplasias Colorretais/sangue , Feminino , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida
4.
Clin Biochem ; 74: 60-68, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31669510

RESUMO

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers worldwide, and emerging lines of evidence have implicated circular RNAs (circRNAs), a novel class of endogenous noncoding RNAs, in CRC development. However, whether plasma circRNAs might be novel diagnostic biomarkers for CRC remains unclear. METHODS: We investigated the plasma levels of selected circRNAs by quantitative real-time PCR (qRT-PCR). The presence of the candidate circRNAs was confirmed through RNase R assays, qRT-PCR and DNA sequencing, and their diagnostic value was evaluated using a receiver operating characteristic (ROC) curve. RESULTS: The plasma levels of three circRNAs (circ-CCDC66, circ-ABCC1 and circ-STIL) were significantly decreased in CRC patients (n = 45) compared with healthy controls (n = 61). The ROC curve analysis showed that the area under the ROC curve (AUC) of the three-circRNA panel was 0.780, which is higher than that of traditional protein biomarkers, such as carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9). Combining the circRNA panel with CEA and CA19-9 might improve the ability to diagnose CRC (AUC = 0.855). In addition, the plasma circ-ABCC1 level was related to tumor growth and progression, and the plasma circ-CCDC66 and circ-ABCC1 levels were decreased in precursor lesions of CRC, including colon adenomas and adenomatous polyps. More importantly, circ-CCDC66 and circ-STIL were found to be useful for diagnosing early-stage CRC, and the three-circRNA panel improved the ability to diagnose CEA-negative and CA19-9-negative CRC. CONCLUSION: Our study provides the first identification of a panel of three plasma circRNAs that could serve as a novel and independent diagnostic biomarker for CRC.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Colorretais/sangue , Neoplasias Colorretais/diagnóstico , /sangue , Adenoma/sangue , Pólipos Adenomatosos/sangue , Idoso , Antígenos Glicosídicos Associados a Tumores/sangue , Biomarcadores Tumorais/genética , Antígeno Carcinoembrionário/sangue , Estudos de Coortes , Neoplasias do Colo/sangue , Detecção Precoce de Câncer , Feminino , Humanos , Modelos Logísticos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real , Análise de Sequência de DNA
5.
J Surg Oncol ; 120(8): 1404-1411, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31646652

RESUMO

BACKGROUND AND OBJECTIVES: The aim was to evaluate the prognostic biomarker potential of the soluble urokinase-type plasminogen activator receptor (suPAR) in plasma samples collected pre- and postoperatively from patients resected for colorectal cancer (CRC). METHODS: Patients with CRC were recruited prospectively at six centers from 2006 to 2008. Preoperative plasma samples were available from 494 patients and from 328 of these patients at 6 months postoperatively. Determinations of intact soluble uPAR (suPAR) suPAR(I-III) and the cleaved forms suPAR(I-III) + (II-III) and uPAR(I) were performed. Clinical data were retrieved retrospectively. RESULTS: In a multivariable model based on preoperative plasma samples suPAR(I-III) + (II-III) and uPAR(I) showed an independent statistically significant association to long term survival. When including the change in biomarker level between the pre- and postoperatively samples the hazard ratios were 3.06 (95% confidence interval [CI], 1.78-5.28; P < .0001) and 2.24 (95% CI, 1.59-3.16; P < .0001) for suPAR(I-III) + (II-III) and uPAR(I), respectively. A one-unit decrease in biomarker levels between the pre- and postoperative levels resulted in a 55% and 34% reduction in the risk estimate of death for suPAR(I-III) + (II-III) and uPAR(I), respectively. CONCLUSION: This study validates previously findings regarding the prognostic significance of suPAR in preoperative samples. The inclusion of postoperative samples added further prognostic information.


Assuntos
Neoplasias Colorretais/sangue , Neoplasias Colorretais/mortalidade , Receptores de Ativador de Plasminogênio Tipo Uroquinase/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Neoplasias Colorretais/cirurgia , Dinamarca/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Estudos Retrospectivos
6.
Zhonghua Wei Chang Wai Ke Za Zhi ; 22(10): 966-971, 2019 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-31630495

RESUMO

Objective: To analyze the clinicopathological features of type 2 diabetes mellitus complicated with colorectal cancer (DCRC). Methods: A case-control study was conducted. Inclusion criteria: (1) hospitalized patients receiving fibrocolonoscopy; (2) adenocarcinoma and mucinous adenocarcinoma diagnosed by pathology; (3) with preoperative cTNM clinical staging; (4) colorectal cancer patients undergoing surgical treatment; (5) with postoperative pTNM staging; (6) no smoking or drinking habits. Exclusion criteria: (1) familial adenomatous polyposis (FAP); (2) Lynch syndrome; (3) carcinoma of anal canal and perianal carcinoma; (4) multiple primary cancer; (5) with serious cardiocerebrovascular diseases or multiple organ failure. Clinicopathlogical data of 32 DCRC patients who were diagnosed and treated in Peking University Shougang Hospital from December 2017 to December 2018 were retrospectively collected and analyzed. Forty nondiabetic colorectal cancer (CRC) patients during the same period were selected as control group according to the sex ratio and the age difference less than 5 years. Student's t test and χ(2) test were used to compare the difference between the two groups in baseline clinicopathological data, clinical test results, tumor markers and infiltration status of T cells in tumor immune microenvironment. Results: Among 32 DCRC patients, 24 were males and 8 were females with a mean age of (63.0±1.7) years; among 40 CRC patients, 30 were males and 10 were females with a mean age of (60.5±1.6) years. The duration of diabetes mellitus in DCRC patients (from the diagnosis of diabetes mellitus to the diagnosis of colorectal cancer) was (9.2±1.3) years. The body mass index (BMI) of DCRC group was significantly higher than that of CRC group [(24.8±0.6) kg/m(2) vs. (23.2±0.4) kg/m(2), t=2.372, P=0.020]. There were no significant differences in other baseline data (sex, age, primary site of tumor, R0 resection rate, pathological stage, pathological type, differentiation degree of tumor, preoperative intestinal obstruction) between the two groups (all P>0.05). Serum triglyceride level in DCRC group was higher than that in CRC group [(2.1±0.2) mmol/L vs. (1.5±0.1) mmol/L, t=3.085, P=0.003], while hemoglobin [(120.3±5.2) g/L vs. (132.7±2.8) g/L, t=-2.224, P=0.029], anti- thrombin III [(94.2±3.7)% vs. (103.5±2.4)%, t=-2.197, P=0.031], and red blood cell count [(4.2±0.1)×10(12)/L vs. (4.5±0.1)×10(12)L, t=-2.055, P=0.044] were all lower than those in CRC group. The preoperative carcinoembryonic antigen (CEA) level in DCRC group was higher than that in CRC group [(50.3±21.8) µg/L vs. (5.6±1.0) µg/L, t=2.339, P=0.022]. There were no significant differences in preoperative levels of other four tumor molecular markers (CA199, CA242, CA724 and CA125) between the two groups (all P>0.05). The expression of Foxp3 [specific markers of CD4+, CD25+ regulatory T cells (Treg)] in DCRC group was higher than that in CRC group [(82.7±6.2) cell/HPF vs. (62.6±4.9) cell/HPF, t=2.586, P=0.012]. There were no significant differences in the infiltration of CD4, CD8, PD-1 and PD-L1 positive cells between two groups (all P>0.05). Conclusions: The average diabetic history of DCRC patients is nearly 10 years. They have higher BMI and serum CEA level, and more Treg cell infiltration in the tumor. Close attention should be paid to these patients in clinical practice.


Assuntos
Neoplasias Colorretais/cirurgia , Diabetes Mellitus Tipo 2/diagnóstico , Adenocarcinoma/sangue , Adenocarcinoma/complicações , Adenocarcinoma/diagnóstico , Adenocarcinoma/cirurgia , Idoso , Índice de Massa Corporal , Antígeno Carcinoembrionário/sangue , Estudos de Casos e Controles , Neoplasias Colorretais/sangue , Neoplasias Colorretais/complicações , Neoplasias Colorretais/diagnóstico , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Linfócitos T Reguladores/imunologia , Microambiente Tumoral/fisiologia
7.
Dis Colon Rectum ; 62(12): 1485-1493, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31567920

RESUMO

BACKGROUND: Systemic inflammation may influence the response to systemic chemotherapy or the prognosis in patients with various cancers. The Naples prognostic score, based on inflammatory and nutritional statuses, is a useful prognostic marker in patients undergoing surgery for colorectal cancer; however, its significance in patients with metastatic colorectal cancer remains unclear. OBJECTIVE: We aimed to evaluate the prognostic significance of the Naples prognostic factor in patients with metastatic colorectal cancer receiving first-line chemotherapy and to compare its prognostic accuracy with the neutrophil:lymphocyte ratio, platelet:lymphocyte ratio, and the systemic immune-inflammatory index. DESIGN: This was a retrospective study of prospectively collected data. SETTINGS: This study was conducted at a university hospital. PATIENTS: A total of 259 patients received first-line systemic chemotherapy for metastatic colorectal cancer. MAIN OUTCOME MEASURES: The Naples prognostic score was calculated by a composite score of albumin and cholesterol concentrations, lymphocyte:monocyte ratio, and neutrophil:lymphocyte ratio. The patients were divided into 3 groups based on increasing Naples scores (groups 0-2), and the associations of the Naples prognostic score with clinicopathologic features and overall survival were evaluated. RESULTS: Higher Naples prognostic score was positively associated with right-sided primary tumors and synchronous metastases and negatively with primary tumor resection. Patients in group 2 (high Naples prognostic score) had significantly shorter overall survival than those in groups 0 and 1 (p = 0.012 and 0.022). Multivariate Cox regression analysis identified the Naples prognostic score as an independent prognostic factor for overall survival (HR = 1.574; p = 0.004). Time-dependent receiver operating characteristic curve analysis showed that Naples prognostic score was more sensitive than other prognostic factors for predicting overall survival. LIMITATIONS: The main limitations are the sample size, single institutional feature, and treatment heterogeneity. CONCLUSIONS: The Naples prognostic score may be a useful prognostic marker in patients with metastatic colorectal cancer receiving systemic chemotherapy. See Video Abstract at http://links.lww.com/DCR/B72. LA PUNTUACIÓN PRONÓSTICA DE NÁPOLES ES UN MARCADOR PRONÓSTICO ÚTIL EN PACIENTES CON CÁNCER COLORRECTAL METASTÁSICO: La inflamación sistémica puede influir en la respuesta a la quimioterapia sistémica o el pronóstico en pacientes con varios tipos de cáncer. La puntuación pronóstica de Nápoles, basada en estados inflamatorios y nutricionales, es un marcador pronóstico útil en pacientes sometidos a cirugía por cáncer colorrectal; sin embargo, su importancia en pacientes con cáncer colorrectal metastásico sigue siendo incierta.El objetivo fue evaluar la importancia pronóstica del factor pronóstico de Nápoles en pacientes con cáncer colorrectal metastásico que reciben quimioterapia de primera línea y comparar su precisión pronóstica con la relación neutrófilos: linfocitos, plaquetas: linfocitos y el índice sistémico inmune-inflamatorio.Este estudio se realizó en un hospital universitario.Este fue un estudio retrospectivo de datos recolectados prospectivamente.Un total de 259 pacientes recibieron quimioterapia sistémica de primera línea para el cáncer colorrectal metastásico.La puntuación pronóstica de Nápoles se calculó mediante una puntuación compuesta de concentraciones de albúmina y colesterol, proporción de linfocitos: monocitos y proporción de neutrófilos: linfocitos. Los pacientes se dividieron en tres grupos basados en el aumento de las puntuaciones de Nápoles (grupos 0-2, respectivamente) y se evaluaron las asociaciones de la puntuación pronóstica de Nápoles con las características clínico-patológicas y la supervivencia general.La puntuación pronóstica de Nápoles es más alta se asoció positivamente con los tumores primarios del lado derecho y metástasis sincrónicas, y negativamente con la resección del tumor primario. Los pacientes del grupo 2 (alto puntaje pronóstico de Nápoles) tuvieron una supervivencia general significativamente menor que los de los grupos 0 y 1 (p = 0.012 y 0.022, respectivamente). El análisis de regresión de Cox multivariado identificó la puntuación pronóstica de Nápoles como un factor pronóstico independiente para la supervivencia global (índice de riesgo = 1.574; p = 0.004). El análisis de la curva característica de funcionamiento del receptor dependiente del tiempo mostró que la puntuación pronóstica de Nápoles era más sensible que otros factores pronósticos para predecir la supervivencia global.Las principales limitaciones son el tamaño de la muestra, la característica institucional única y la heterogeneidad del tratamiento.La puntuación pronóstica de Nápoles puede ser un marcador pronóstico útil en pacientes con cáncer colorrectal metastásico que reciben quimioterapia sistémica. Vea el Abstract del video en http://links.lww.com/DCR/B72.


Assuntos
Biomarcadores Tumorais/imunologia , Neoplasias Colorretais/tratamento farmacológico , Estado Nutricional , Adulto , Idoso , Idoso de 80 Anos ou mais , Colesterol/sangue , Neoplasias Colorretais/sangue , Tratamento Farmacológico , Feminino , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Contagem de Plaquetas , Prognóstico , Curva ROC , Estudos Retrospectivos , Tamanho da Amostra , Albumina Sérica Humana/análise , Resultado do Tratamento
8.
Medicine (Baltimore) ; 98(37): e16974, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31517816

RESUMO

BACKGROUND: Growing evidence showed that high pretreatment plasma fibrinogen could be used as a potential prognostic marker in colorectal cancer (CRC). However, the conclusions were controversial. Therefore, this meta-analysis was conducted to evaluate the prognostic value of pretreatment plasma fibrinogen in patients with CRC. METHODS: Relevant studies were searched in the databases including PubMed, EMBASE, Web of Science, Cochrane library, and China National Knowledge Infrastructure up until December 10th, 2018. Pooled hazard ratios (HRs) with their 95% confidence intervals (CIs) were used to estimate the effects. RESULTS: A total of 17 articles with 6863 patients were included in this meta-analysis. The results revealed that elevated pretreatment plasma fibrinogen was significantly associated with both poor overall survival (univariate analysis: HR = 1.69, 95% CI 1.47-1.95, P = .000; multivariate analysis: HR = 1.50, 95% CI 1.28-1.77, P = .000) and poor disease-free survival (univariate analysis: HR = 1.90, 95% CI 1.49-2.41, P = .000; multivariate analysis: HR = 2.08, 95% CI 1.52-2.86, P = .000) in patients with CRC. CONCLUSIONS: High pretreatment plasma fibrinogen level is significantly associated with worse survival outcomes in CRC patients. Plasma fibrinogen may be used as an effective prognostic marker and potential therapeutic target. Further studies are required to support these results.


Assuntos
Neoplasias Colorretais/sangue , Fibrinogênio/análise , Biomarcadores/sangue , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/terapia , Humanos , Prognóstico
9.
Cell Mol Biol (Noisy-le-grand) ; 65(6): 44-51, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31472046

RESUMO

This study was carried out to investigate cell-free DNA (cfDNA) as a potential biomarker for colorectal cancer diagnosis.Patients with colorectal cancer (n = 25) who had not undergone surgery, and 35 patients with postoperative colorectal cancer were enrolled. Peripheral blood samples were collected from the colorectal cancer subjects (experimental group), and also from 30 healthy volunteers (control group). Quantitative PCR (qPCR) was used to determine cfDNA concentration and integrity in each group. The cfDNA levels of the two groups were analyzed to determine the relationship between the cfDNA and the clinical features of colorectal cancer patients. The receiver operator curve (ROC) was used to analyze sensitivity and specificity of cfDNA, carcinoembryonic antigen (CEA), cancer antigen 199 (CA199) and cancer antigen 125 (CA125). cfDNA concentration and cfDNA integrity in patients with colorectal cancer before surgery were significantly higher than those in patients with colorectal cancer after surgery, and cfDNA concentration of colorectal cancer patients after surgery was also significantly higher than that of the healthy control group, but the integrity was not significantly different from the control group. There was no significant correlation between cfDNA concentration/integrity and gender, age, disease stage, tumor location, tumor differentiation, and expressions of cancer antigen 153 (CA153), neuron specific enolase (NSE) and alpha fetoprotein (AFP) in colorectal cancer patients before or after surgery. However, there was a significant correlation between the expression levels of CEA/CA125 and concentration of cfDNA. The CA199 expression level was significantly correlated with cfDNA integrity. The sensitivity and specificity of cfDNA and integrity were higher than those used for traditional tumor biomarker detection. cfDNA concentration is significantly increased in serum of colorectal cancer patients. Thus, it may serve as a potential indicator of colorectal cancer.


Assuntos
Ácidos Nucleicos Livres/sangue , Neoplasias Colorretais/sangue , Neoplasias Colorretais/cirurgia , Adulto , Idoso , Cirurgia Colorretal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC
10.
Nat Med ; 25(9): 1428-1441, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31501614

RESUMO

Psychological distress has long been suspected to influence cancer incidence and mortality. It remains largely unknown whether and how stress affects the efficacy of anticancer therapies. We observed that social defeat caused anxiety-like behaviors in mice and dampened therapeutic responses against carcinogen-induced neoplasias and transplantable tumors. Stress elevated plasma corticosterone and upregulated the expression of glucocorticoid-inducible factor Tsc22d3, which blocked type I interferon (IFN) responses in dendritic cell (DC) and IFN-γ+ T cell activation. Similarly, close correlations were discovered among plasma cortisol levels, TSC22D3 expression in circulating leukocytes and negative mood in patients with cancer. In murine models, exogenous glucocorticoid injection, or enforced expression of Tsc22d3 in DC was sufficient to abolish therapeutic control of tumors. Administration of a glucocorticoid receptor antagonist or DC-specific Tsc22d3 deletion reversed the negative impact of stress or glucocorticoid supplementation on therapeutic outcomes. Altogether, these results indicate that stress-induced glucocorticoid surge and Tsc22d3 upregulation can subvert therapy-induced anticancer immunosurveillance.


Assuntos
Imunidade Celular , Neoplasias/imunologia , Estresse Psicológico/imunologia , Fatores de Transcrição/genética , Animais , Ansiedade/sangue , Ansiedade/induzido quimicamente , Ansiedade/imunologia , Ansiedade/psicologia , Comportamento Animal/fisiologia , Carcinógenos/toxicidade , Neoplasias Colorretais/sangue , Neoplasias Colorretais/genética , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/psicologia , Corticosterona/sangue , Células Dendríticas/transplante , Regulação Neoplásica da Expressão Gênica , Glucocorticoides/farmacologia , Humanos , Hidrocortisona/sangue , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/psicologia , Ativação Linfocitária/genética , Camundongos , Monitorização Imunológica/métodos , Neoplasias/induzido quimicamente , Neoplasias/genética , Neoplasias/psicologia , Receptores de Glucocorticoides/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Neoplasias Gástricas/sangue , Neoplasias Gástricas/genética , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/psicologia , Estresse Psicológico/induzido quimicamente , Estresse Psicológico/genética , Estresse Psicológico/terapia , Fatores de Transcrição/imunologia
11.
Int J Mol Sci ; 20(16)2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31409008

RESUMO

The chemoattractant adipokine chemerin is related to the metabolic syndrome, which is a risk factor for different cancers. Recent studies provide evidence that chemerin is an important molecule in colorectal cancer (CRC) and hepatocellular carcinoma (HCC). Serum chemerin is high in CRC patients and low in HCC patients and may serve as a differential diagnostic marker for HCC and liver metastases from CRC. To this end, serum chemerin was measured in 36 patients with CRC metastases, 32 patients with HCC and 49 non-tumor patients by ELISA. Chemerin serum protein levels were, however, similar in the three cohorts. Serum chemerin was higher in hypertensive than normotensive tumor patients but not controls. Cancer patients with hypercholesterolemia or hyperuricemia also had increased serum chemerin. When patients with these comorbidities were excluded from the calculation, chemerin was higher in CRC than HCC patients but did not differ from controls. Chemerin did not correlate with the tumor markers carcinoembryonic antigen, carbohydrate antigen 19-9 and alpha-fetoprotein in both cohorts and was not changed with tumor-node-metastasis stage in HCC. Chemerin was not associated with hepatic fat, liver inflammation and fibrosis. To conclude, systemic chemerin did not discriminate between CRC metastases and HCC. Comorbidities among tumor patients were linked with elevated systemic chemerin.


Assuntos
Carcinoma Hepatocelular/secundário , Quimiocinas/sangue , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/diagnóstico , Neoplasias Colorretais/sangue , Feminino , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/diagnóstico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
12.
Arq Gastroenterol ; 56(2): 172-177, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31460582

RESUMO

BACKGROUND: Considering the high incidence of colorectal cancer (CRC) related deaths, many studies have investigated variables that can affect survival, with the aim of prolonging survival. The nutritional status can also be predict survival in patients with CRC. OBJECTIVE: The aim of the present study was to evaluate if BMI, %FAT, PhA, PG-SGA, adiponectin levels, and vitamin D levels are relevant to the characterization and differentiation of patients with advanced CRC and patients with a history of CRC. METHODS: The study was carried out by patients with advanced colorectal cancer (Group 1) and patients in follow-up after colorectal cancer treatment (Group 2). Nutritional status was assessed using the body mass index, body fat percentage, phase angle from bioelectrical impedance, Patient-Generated Subjective Global Assessment score. Adiponectin concentrations were determined using an enzyme-linked immunosorbent assay, and vitamin D levels were measured using high performance liquid chromatography. RESULTS: Groups 1 and 2 consisted of 23 and 27 patients, respectively. The body mass index, body fat percentage, phase angle, vitamin D and adiponectin levels were not significantly different between the groups. The mean Patient-Generated Subjective Global Assessment score was significantly higher in group 1 compared with group 2, and was significantly correlated with the long-term mortality risk. CONCLUSION: Among the nutritional status parameters, only the Patient-Generated Subjective Global Assessment score was significantly different between the groups and was an important predictor of survival in patients with advanced colorectal cancer.


Assuntos
Adiponectina/sangue , Neoplasias Colorretais/sangue , Estado Nutricional , Vitamina D/sangue , Idoso , Índice de Massa Corporal , Neoplasias Colorretais/mortalidade , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias
13.
Int J Nanomedicine ; 14: 6165-6178, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31447558

RESUMO

Purpose: Surface-enhanced Raman scattering (SERS) spectroscopy on serum and other biofluids for cancer diagnosis represents an emerging field, which has shown promising preliminary results in several types of malignancies. The purpose of this study was to demonstrate that SERS spectroscopy on serum can be employed for the differential diagnosis between five of the leading malignancies, ie, breast, colorectal, lung, ovarian and oral cancer. Patients and methods: Serum samples were acquired from healthy volunteers (n=39) and from patients diagnosed with breast (n=42), colorectal (n=109), lung (n=33), oral (n=17), and ovarian cancer (n=13), comprising n=253 samples in total. SERS spectra were acquired using a 532 nm laser line as excitation source, while the SERS substrates were represented by Ag nanoparticles synthesized by reduction with hydroxylamine. The classification accuracy yielded by SERS was assessed by principal component analysis-linear discriminant analysis (PCA-LDA). Results: The sensitivity and specificity in discriminating between cancer patients and controls was 98% and 91%, respectively. Cancer samples were correctly assigned to their corresponding cancer types with an accuracy of 88% for oral cancer, 86% for colorectal cancer, 80% for ovarian cancer, 76% for breast cancer and 59% for lung cancer. Conclusion: SERS on serum represents a promising strategy of diagnosing cancer which can discriminate between cancer patients and controls, as well as between cancer types such as breast, colorectal, lung ovarian and oral cancer.


Assuntos
Neoplasias/diagnóstico , Análise Espectral Raman/métodos , Idoso , Neoplasias da Mama/sangue , Neoplasias da Mama/diagnóstico , Estudos de Casos e Controles , Neoplasias Colorretais/sangue , Neoplasias Colorretais/diagnóstico , Diagnóstico Diferencial , Análise Discriminante , Feminino , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/diagnóstico , Masculino , Nanopartículas Metálicas/química , Nanopartículas Metálicas/ultraestrutura , Pessoa de Meia-Idade , Neoplasias Bucais/sangue , Neoplasias Bucais/diagnóstico , Neoplasias/sangue , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/diagnóstico , Análise de Componente Principal , Prata/química
14.
Biomed Res Int ; 2019: 9852782, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31467924

RESUMO

Background and Aim: Colorectal cancer (CRC) is the third most lethal cancer globally. This study sought to determine the feasibility of using red cell distribution width-to-lymphocyte ratio (RLR) as a tool to facilitate CRC detection. Methods: Seventy-eight healthy controls, 162 patients diagnosed with CRC, and 94 patients with colorectal polyps (CP) from June 2017 to October 2018 were retrospectively reviewed. Clinical data were obtained to analyze preoperative RLR level, and receiver operating characteristic (ROC) curve analysis was performed to estimate the potential role of RLR as a CRC biomarker. Results: RLR was higher in patients with CRC than in healthy participants (P < 0.05). ROC analysis indicated that combined detection of RLR and CEA appears to be a more effective marker to distinguish among controls, CP, and CRC patients, yielding 56% sensitivity and 90% specificity. RLR levels were significantly greater in those who had more advanced TNM stages (P < 0.05) and patients with distant metastasis stages (P < 0.05). Conclusions: RLR might serve as a potential biomarker for CRC diagnosis.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Colorretais/sangue , Índices de Eritrócitos/genética , Idoso , Antígenos Glicosídicos Associados a Tumores/sangue , Antígeno Carcinoembrionário/sangue , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Detecção Precoce de Câncer , Feminino , Humanos , Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade
15.
BMC Cancer ; 19(1): 832, 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31443703

RESUMO

BACKGROUND: Blood-based methods using cell-free DNA (cfDNA) are under development as an alternative to existing screening tests. However, early-stage detection of cancer using tumor-derived cfDNA has proven challenging because of the small proportion of cfDNA derived from tumor tissue in early-stage disease. A machine learning approach to discover signatures in cfDNA, potentially reflective of both tumor and non-tumor contributions, may represent a promising direction for the early detection of cancer. METHODS: Whole-genome sequencing was performed on cfDNA extracted from plasma samples (N = 546 colorectal cancer and 271 non-cancer controls). Reads aligning to protein-coding gene bodies were extracted, and read counts were normalized. cfDNA tumor fraction was estimated using IchorCNA. Machine learning models were trained using k-fold cross-validation and confounder-based cross-validations to assess generalization performance. RESULTS: In a colorectal cancer cohort heavily weighted towards early-stage cancer (80% stage I/II), we achieved a mean AUC of 0.92 (95% CI 0.91-0.93) with a mean sensitivity of 85% (95% CI 83-86%) at 85% specificity. Sensitivity generally increased with tumor stage and increasing tumor fraction. Stratification by age, sequencing batch, and institution demonstrated the impact of these confounders and provided a more accurate assessment of generalization performance. CONCLUSIONS: A machine learning approach using cfDNA achieved high sensitivity and specificity in a large, predominantly early-stage, colorectal cancer cohort. The possibility of systematic technical and institution-specific biases warrants similar confounder analyses in other studies. Prospective validation of this machine learning method and evaluation of a multi-analyte approach are underway.


Assuntos
Biomarcadores Tumorais , DNA Tumoral Circulante , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Genoma Humano , Genômica , Aprendizado de Máquina , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/sangue , Biologia Computacional/métodos , Feminino , Perfilação da Expressão Gênica , Genômica/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Curva ROC , Reprodutibilidade dos Testes , Transcriptoma
16.
Anticancer Res ; 39(8): 4343-4350, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366528

RESUMO

BACKGROUND/AIM: TAS-102 is recommended as salvage-line therapy for metastatic colorectal cancer (mCRC), but practical predictors for its efficacy are lacking. PATIENTS AND METHODS: In a single-institutional retrospective study of 33 patients treated with TAS-102, we investigated the predictive value of the pretreatment neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR), and lymphocyte-monocyte (LMR) ratios for progression-free (PFS) and overall (OS) survival. Predictive ability using cut-offs of the median value (3.14) and 5 for NLR were compared. RESULTS: In univariate analysis, Eastern Cooperative Oncology Group performance score, NLR, and PLR were negatively significantly associated with PFS and OS. The number of treatment lines was negatively associated with PFS. The NLR cut-off of 5 was superior to the median value. Multivariate analyses showed a significant prognostic impact for NLR at cut-off 5 (hazard ratio(HR)=6.26, p=0.02 for PFS; HR=6.97, p=0.07 for OS). CONCLUSION: The pretreatment NLR is a prognostic biomarker for patients with mCRC who receive TAS-102 treatment.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Colorretais/tratamento farmacológico , Prognóstico , Trifluridina/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/sangue , Neoplasias Colorretais/patologia , Combinação de Medicamentos , Feminino , Humanos , Contagem de Leucócitos , Contagem de Linfócitos , Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neutrófilos/patologia , Contagem de Plaquetas , Intervalo Livre de Progressão , Pirrolidinas , Estudos Retrospectivos , Uracila/análogos & derivados
17.
Surgery ; 166(4): 534-539, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31378479

RESUMO

BACKGROUND: Liquid biopsy is a new area in cancer diagnostics that measures cell-free DNA in plasma from tumor that may serve as a monitoring tool in colorectal cancer patients. METHODS: Multiplexed real-time polymerase chain reaction based on multicopy retro-transposable elements (targeting 80 base pair and 265 base pair sequences and an internal-positive-control) was used to evaluate the ability of cell-free DNA concentration and DNA Integrity Index to discriminate cancer from healthy patients. A cohort of 40 healthy controls and 39 stage IV colorectal patient's plasma were interrogated. The potency of each biomarker was measured by using receiver operating characteristic curves and derived area under the curve measures. RESULTS: Significant differences in cell-free DNA concentration and DNA integrity index were observed between controls and stage IV patients with a limit of detection <0.1 pg/µL. Investigation of the ability of both biomarker candidates to differentiate cancer from healthy patients showed an area under the curve of 0.9891 and 0.9859 for 80 base pair and 265 amplicons respectively and 0.8603 for DNA integrity index-265/80. CONCLUSIONS: After establishing differences in cell-free DNA levels between healthy and treated and untreated stage IV patients, the multiplexed real-time polymerase chain reaction measurements of retro-transposable elements in cancer patient plasma potentially possess the ability to monitor therapy responsiveness in near real time.


Assuntos
Ácidos Nucleicos Livres/análise , Neoplasias Colorretais/sangue , Neoplasias Colorretais/patologia , Reação em Cadeia da Polimerase em Tempo Real/métodos , Idoso , Área Sob a Curva , Biomarcadores Tumorais/sangue , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica/métodos , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Curva ROC , Valores de Referência , Sensibilidade e Especificidade
18.
Orv Hetil ; 160(30): 1167-1177, 2019 Jul.
Artigo em Húngaro | MEDLINE | ID: mdl-31327245

RESUMO

The incidence and mortality of colorectal cancer (CRC) are considerably high in Central European countries, it is the second most common cancer in both men and women in Hungary with 10,000 newly registered patients per year. These data indicate the necessity of new screening methods that are more comfortable for patients, hence the compliance can be increased. Cell-free DNA (cfDNA) level in blood is elevated in certain physiological conditions, such as pregnancy or high physical activity. Furthermore, cfDNA concentration alterations can also be detected in some pathological processes; increased cfDNA amount was observed in autoimmune and inflammatory diseases, as well as in various cancers including CRC. Numerous studies about origin, function, and mechanism of cfDNA can be found in the scientific literature. In this review, we aimed to describe the quantitative and qualitative changes of cfDNA, to present its functions, and to provide an overview of the available diagnostic applications for CRC. CfDNA can be released to the circulatory system via apoptosis, necrosis or by direct secretions by living cells. In cancer patients, cfDNA can originate from healthy and cancer cells, hence genetic (e.g. mutations in APC, KRAS, BRAF) and epigenetic (e.g. methylation in SEPT9, SFRP1) alterations of tumor cells can be examined in cfDNA fraction. Several high-throughput, sensitive and even automated methods are available providing opportunity to perform standardized sample preparation and to analyse biomarker candidates quantitatively. These enhancements can help to develop alternative screening methods that can be easily integrated into the clinical practice and can contribute to early cancer detection. Orv Hetil. 2019; 160(30): 1167-1177.


Assuntos
Biomarcadores Tumorais/sangue , Ácidos Nucleicos Livres/genética , Neoplasias Colorretais/diagnóstico , DNA de Neoplasias/genética , Biomarcadores Tumorais/genética , Neoplasias Colorretais/sangue , Metilação de DNA , DNA de Neoplasias/sangue , Feminino , Humanos , Hungria , Masculino
19.
Genet Test Mol Biomarkers ; 23(8): 509-514, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31328973

RESUMO

Background: Long noncoding RNAs (lncRNAs) have recently been recognized as a new layer of biological regulation. They participate in mRNA regulation and may be useful as prognostic factors and drug targets. Colorectal cancer (CRC) is a common tumor that is characterized by its high mortality rate. Despite improvements in screening of CRC, the prognosis is still poor. Therefore, there is an urgent need to develop effective biomarkers for the detection of CRC. This study was designed to measure the expression of several oncogenic lncRNAs, including PANDAR, MALAT1, PCAT6, CCAT1, UCA1, MEG3, CCAT2, and BCAR4, in blood samples of healthy individuals and CRC patients. Methods: Total RNA was isolated from whole blood of 63 CRC patients and 40 controls and the expression of the lncRNAs was determined by real-time polymerase chain reaction and measured by REST2009 software. All p-values <0.05 were considered statistically significant. Results: The results showed that the expression levels of MALAT1, CCAT1, and PANDAR were significantly upregulated with 1.86, 4.54, and 4.68-fold higher levels (p < 0.05), respectively, in the blood of CRC patients compared to the controls. However, the other lncRNAs examined were not significantly expressed differentially in CRC blood samples. Conclusion: The findings of this study suggest that the expression of MALAT1, CCAT1, and PANDAR in blood could serve as potential biomarkers for CRC prognosis.


Assuntos
Neoplasias Colorretais/diagnóstico , RNA Longo não Codificante , RNA Neoplásico , Adulto , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Constituição Corporal , Neoplasias Colorretais/sangue , Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real , Arábia Saudita , Regulação para Cima
20.
Medicine (Baltimore) ; 98(29): e16064, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31335668

RESUMO

OBJECTIVE: This meta-analysis evaluates the prognosis value of C-reactive protein to albumin ratio (CAR) in colorectal cancer. METHODS: Embase, PubMed, and Web of Science were searched. Pooled hazard ratios (HRs) with their corresponding 95% confidence intervals (CIs) were used as effective values. RESULTS: A total of 6 studies with 1942 patients were included in this study. Pooled results revealed that elevated pretreatment CAR was related with poorer overall survival (OS) (HR: 2.09, 95%CI: 1.78-2.45, P < .001) in colorectal cancer. CONCLUSION: Elevated CAR was associated with poor prognosis in colorectal cancer. Thus CAR might be used as a prognostic system and classification of colorectal patients in clinical potential.


Assuntos
Proteína C-Reativa/análise , Neoplasias Colorretais , Albumina Sérica/análise , Neoplasias Colorretais/sangue , Neoplasias Colorretais/diagnóstico , Humanos , Prognóstico
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