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1.
Anticancer Res ; 41(4): 1761-1769, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33813380

RESUMO

BACKGROUND: Clinical significance of plasma urothelial carcinoma associated 1 (UCA1) in patients with colorectal cancer (CRC) remains unclear. This study investigated the usefulness of plasma UCA1 as a biomarker in patients with CRC. MATERIALS AND METHODS: UCA1 levels were measured in the plasma and tissue from patients with CRC by quantitative polymerase chain reaction. Relationships between plasma UCA1 and clinicopathological features were examined. RESULTS: Plasma UCA1 levels were significantly lower in patients with CRC than in healthy volunteers. UCA1 expression in B-Raf proto-oncogene serine/threonine kinase (BRAF)-mutant CRC tissue was also lower than that in non-cancerous tissue, although it was higher in CRC with wild-type BRAF. In right-sided CRC, a lower plasma UCA1 level was associated with pT4 and BRAF mutation. In contrast, in left-sided CRC, higher plasma UCA1 was associated with pT4 and pStage 3b-4. CONCLUSION: Plasma UCA1 is a useful biomarker for CRC detection and predicting clinicopathological features, particularly BRAF mutation.


Assuntos
Biomarcadores Tumorais/genética , Ácidos Nucleicos Livres/genética , Neoplasias Colorretais/genética , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , RNA Longo não Codificante/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Estudos de Casos e Controles , Ácidos Nucleicos Livres/sangue , Neoplasias Colorretais/sangue , Neoplasias Colorretais/patologia , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fenótipo , RNA Longo não Codificante/sangue
2.
Anticancer Res ; 41(3): 1421-1428, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33788733

RESUMO

BACKGROUND/AIM: The current study aimed to evaluate the clinical utility of the levels of the C-X-C-motif chemokine receptor-2 (CXCR-2) serum receptor in comparison to the carcinoembryonic antigen (CEA) tumor marker and - the C-reactive protein (CRP) inflammatory marker in the diagnosis and prognosis of colorectal cancer (CRC). MATERIALS AND METHODS: Our study comprised 59 patients with CRC and 46 healthy subjects. Serum concentrations of the analyzed proteins were measured using enzyme-linked immunosorbent assay, chemiluminescent microparticle immunoassay and immunoturbidimetric methods. RESULTS: Serum levels of CXCR-2 were lower, while those of CEA and CRP were significantly higher in CRC patients in comparison to the control group. The diagnostic sensitivity of CXCR-2 was higher than that of CEA, and increased when CXCR-2 analysis was combined with CEA or CRP. CONCLUSION: According to our knowledge, this is the first study concerning the significance of CXCR2 as a CRC biomarker. Measurement of the serum levels of CXCR-2 may improve the diagnosis efficiency of CRC patients, especially in combination with the tumor marker CEA.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Colorretais/sangue , Receptores de Interleucina-8B/sangue , Proteína C-Reativa/análise , Antígeno Carcinoembrionário/sangue , Neoplasias Colorretais/diagnóstico , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Prognóstico , Curva ROC
3.
Anticancer Res ; 41(3): 1593-1598, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33788754

RESUMO

BACKGROUND/AIM: We previously showed that an elevated postoperative serum C-reactive protein (CRP) level has a negative impact on long-term survival outcomes, regardless of the occurrence of infectious complications in colorectal cancer. However, the cause of postoperative inflammation could not be properly evaluated, because patient background factors, such as the surgical approach (open/laparoscopic), were not unified. PATIENTS AND METHODS: A total of 277 patients who underwent laparoscopic surgery for stage II/III colorectal cancer were enrolled. RESULTS: The high-CRP group had lower relapse-free and overall survival rates in comparison to the low-CRP group. A high postoperative serum CRP level was significantly associated with a larger tumor diameter and longer operation time, and tended to be associated with a higher T stage and larger amount of bleeding. CONCLUSION: Larger tumor volume, longer operation time and larger amount of bleeding were associated with the promotion of postoperative inflammation, which worsened long-term survival outcomes in colorectal cancer.


Assuntos
Infecções Bacterianas/sangue , Proteína C-Reativa/análise , Neoplasias Colorretais/cirurgia , Laparoscopia/efeitos adversos , Complicações Pós-Operatórias/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções Bacterianas/mortalidade , Neoplasias Colorretais/sangue , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Complicações Pós-Operatórias/mortalidade , Adulto Jovem
4.
Int J Mol Sci ; 22(3)2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33530402

RESUMO

Blood-based protein biomarkers are increasingly being explored as supplementary or efficient alternatives for population-based screening of colorectal cancer (CRC). The objective of the current study was to compare the diagnostic potential of proteins measured with different proteomic technologies. The concentrations of protein biomarkers were measured using proximity extension assays (PEAs), liquid chromatography/multiple reaction monitoring-mass spectrometry (LC/MRM-MS) and quantibody microarrays (QMAs) in plasma samples of 56 CRC patients and 99 participants free of neoplasms. In another approach, proteins were measured in serum samples of 30 CRC cases and 30 participants free of neoplasm using immunome full-length functional protein arrays (IpAs). From all the measurements, 9, 6, 35 and 14 protein biomarkers overlapped for comparative evaluation of (a) PEA and LC/MRM-MS, (b) PEA and QMA, (c) PEA and IpA, and (d) LC/MRM-MS and IpA measurements, respectively. Correlation analysis was performed, along with calculation of the area under the curve (AUC) for assessing the diagnostic potential of each biomarker. DeLong's test was performed to assess the differences in AUC. Evaluation of the nine biomarkers measured with PEA and LC/MRM-MS displayed correlation coefficients >+0.6, similar AUCs and DeLong's p-values indicating no differences in AUCs for biomarkers like insulin-like growth factor binding protein 2 (IGFBP2), matrix metalloproteinase 9 (MMP9) and serum paraoxonase lactonase 3 (PON3). Comparing six proteins measured with PEA and QMA showed good correlation and similar diagnostic performance for only one protein, growth differentiation factor 15 (GDF15). The comparison of 35 proteins measured with IpA and PEA and 14 proteins analyzed with IpA and LC/MRM-MS revealed poor concordance and comparatively better AUCs when measured with PEA and LC/MRM-MS. The comparison of different proteomic technologies suggests the superior performance of novel technologies like PEA and LC/MRM-MS over the assessed array-based technologies in blood-protein-based early detection of CRC.


Assuntos
Biomarcadores Tumorais/sangue , Proteínas Sanguíneas , Neoplasias Colorretais/sangue , Neoplasias Colorretais/diagnóstico , Proteômica/métodos , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Cromatografia Líquida , Colonoscopia , Neoplasias Colorretais/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Espectrometria de Massas em Tandem
5.
Biomed Res Int ; 2021: 3905353, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33521127

RESUMO

Background: The objective of this study was to explore the role of preoperative fibrinogen-to-prealbumin ratio (FPR) in evaluating the prognosis of patients with stage I-III colorectal cancer (CRC). Methods: This retrospective study enrolled 584 stage I-III CRC patients undergoing surgical resection. Logistic regression analysis was used to explore the correlation between FPR and postoperative complications. The Kaplan-Meier curve and Cox proportional hazards model were used to identify the prognostic factors. The nomograms were constructed based on the prognostic factors. The concordance index and calibration curve were used to determine the accuracy of the nomograms. Time-dependent receiver operating characteristic was used to compare the predictive prognostic efficacy of nomograms and TNM stage. Results: FPR was determined to be an independent factor affecting postoperative complications. Patients with a low-FPR had a significantly better prognosis than those with a high-FPR (disease-free survival, p = 0.028; overall survival, p = 0.027), especially patients with stage I CRC (disease-free survival, p = 0.015; overall survival, p = 0.017). The Cox proportional hazards model identified FPR as an independent poor prognostic factor of disease-free survival (hazard ratio (HR) = 1.459, 95% confidence interval (CI) = 1.074-1.954, p = 0.011) and overall survival (HR = 1.405, 95% CI = 1.034-1.909, p = 0.030). The prognostic nomograms had good accuracy and were superior to the traditional TNM stage. Conclusions: FPR is a potential indicator for predicting short- and long-term prognosis of stage I-III CRC patients undergoing surgical resection.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Colorretais/sangue , Neoplasias Colorretais/diagnóstico , Fibrinogênio/análise , Pré-Albumina/análise , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/cirurgia , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Período Pós-Operatório , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Análise de Regressão , Estudos Retrospectivos , Adulto Jovem
6.
Anticancer Res ; 41(1): 429-436, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33419840

RESUMO

BACKGROUND/AIM: The Aspartate aminotransaminase/Alanine aminotransaminase ratio (AST/ALT ratio) has been identified as a prognostic marker for several malignancies. In this study, we evaluated the prognostic value of the AST/ALT ratio in a large cohort of non-metastatic colorectal cancer patients (CRC). PATIENTS AND METHODS: A total of 536 patients with stage II and III CRC, as well as available AST/ALT ratio were included in this single-center retrospective analysis. Laboratory data were measured within two weeks before histological tumor diagnosis. Co-Primary endpoints for this analysis were disease-free survival (DFS) and overall survival (OS). RESULTS: In univariate cox regression DFS was significantly shorter in patients with an elevated AST/ALT ratio (HR=1.568, 95%CI=1.10-2.23, p=0.012). In multivariable analysis, the prognostic association between an elevated AST/ALT ratio and a poor survival prevailed statistically significant (HR=1.53, 95%C=1.05-2.22, p=0.026). No statistically significant association between the AST/ALT ratio and OS was observed (HR=1.4, 95% CI=0.89-2.22, p=0.14). CONCLUSION: In this study, the serum AST/ALT ratio emerged as a valid prognostic marker for DFS in non-metastatic colorectal cancer patients at stage II and III.


Assuntos
Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Biomarcadores Tumorais , Neoplasias Colorretais/sangue , Neoplasias Colorretais/mortalidade , Idoso , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Resultado do Tratamento
7.
Molecules ; 26(2)2021 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-33477309

RESUMO

User-friendly, low-cost equipment for preventive screening of severe or deadly pathologies are one of the most sought devices by the National Health Services, as they allow early disease detection and treatment, often avoiding its degeneration. In recent years more and more research groups are developing devices aimed at these goals employing gas sensors. Here, nanostructured chemoresistive metal oxide (MOX) sensors were employed in a patented prototype aimed to detect volatile organic compounds (VOCs), exhaled by blood samples collected from patients affected by colorectal cancer and from healthy subjects as a control. Four sensors, carefully selected after many years of laboratory tests on biological samples (cultured cells, human stools, human biopsies, etc.), were based here on various percentages of tin, tungsten, titanium, niobium, tantalum and vanadium oxides. Sensor voltage responses were statistically analyzed also with the receiver operating characteristic (ROC) curves, that allowed the identification of the cut-off discriminating between healthy and tumor affected subjects for each sensor, leading to an estimate of sensitivity and specificity parameters. ROC analysis demonstrated that sensors employing tin and titanium oxides decorated with gold nanoparticles gave sensitivities up to 80% yet with a specificity of 70%.


Assuntos
Neoplasias Colorretais/sangue , Nanopartículas Metálicas/química , Microscopia Eletroquímica de Varredura , Nióbio/química , Tantálio/química , Estanho/química , Vanádio/química , Compostos Orgânicos Voláteis/sangue , Adulto , Feminino , Humanos , Masculino
8.
Am J Surg ; 221(1): 162-167, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32746979

RESUMO

BACKGROUND: Chronic kidney disease (CKD) can increase serum carcinoembryonic antigen (CEA) levels. We thus aimed to evaluate the impact of CKD on CEA prognostic accuracy in colorectal cancer. METHODS: Altogether, 429 patients who underwent curative resection for stages I-III colorectal adenocarcinoma were grouped according to postoperative CEA levels and history of CKD. RESULTS: Three-year disease-free survival (DFS) was higher in patients with normal postoperative CEA (group A, 83.4%) than in those with elevated postoperative CEA (group B, 64.3%) (p < 0.001). CKD patients had higher postoperative CEA levels than non-CKD patients (odds ratio 3.27, 95% confidence interval 1.78-5.99, p < 0.001). In multivariable analysis, postoperative CEA level was an independent prognostic factor for DFS in non-CKD, but not CKD, patients. CONCLUSIONS: CKD can increase postoperative CEA levels in colorectal cancer patients. Elevated postoperative CEA levels were associated with shorter DFS in non-CKD, but not CKD, patients.


Assuntos
Adenocarcinoma/sangue , Adenocarcinoma/mortalidade , Antígeno Carcinoembrionário/sangue , Neoplasias Colorretais/sangue , Neoplasias Colorretais/mortalidade , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/complicações , Adenocarcinoma/complicações , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/complicações , Neoplasias Colorretais/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Prognóstico , Estudos Retrospectivos
9.
PLoS One ; 15(12): e0243643, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33370317

RESUMO

Monocytic myeloid-derived suppressor cells (mMDSCs) are a class of immunosuppressive immune cells with prognostic value in many solid tumors. It is reported that the proportion of mMDSCs in the peripheral blood can be a predictive marker for response to cancer immunotherapy. In this study, we performed a correlation analysis of the proportion of mMDSCs in freshly-drawn peripheral blood, levels of plasma proteins, and demographic factors in colorectal cancer (CRC) patients, to find factors that could be used to predict mMDSC proportions. Freshly-drawn mMDSCs were measured using flow cytometry on peripheral blood mononuclear cells (PBMCs) from healthy donors (n = 24) and CRC patients (n = 78). The plasma concentrations of 29 different cytokines, chemokines, growth factors, and enzymes were measured using a multiplex assay or enzyme-linked immunosorbent assay. Correlation analysis to find mMDSC-associated factors was conducted using univariate and multivariate models. In univariate correlation analysis, there were no plasma proteins that were associated with mMDSC proportions in CRC patients. In multivariate analysis, considering all variables including age, sex, and plasma proteins, levels of inducible nitric acid synthase (iNOS) (p = 0.013) and platelet-derived growth factor (PDGF)-BB (p = 0.035) were associated with mMDSC proportion in PBMCs (mMDSC proportion [%] = 0.2929 - 0.2389 * PDGF-BB + 0.3582 * iNOS) (p < 0.005, r = 0.32). Measuring the plasma concentrations of iNOS and PDGF-BB may be useful in predicting the proportion of mMDSCs in CRC patients' peripheral blood. Further research is required to establish and validate these predictive factors. Data registration Patient data were registered in an anonymization system at Tsukuba Clinical Research & Development Organization (T-CReDO).


Assuntos
Neoplasias Colorretais/patologia , Leucócitos Mononucleares/patologia , Células Supressoras Mieloides/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Células Cultivadas , Neoplasias Colorretais/sangue , Citocinas/sangue , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade
10.
Rev. esp. enferm. dig ; 112(11): 832-837, nov. 2020. tab, graf
Artigo em Inglês | IBECS | ID: ibc-198766

RESUMO

OBJECTIVE: this study aimed to investigate the expression and clinical significance of miR-21 and miR-210 in serum of patients with colorectal cancer (CRC). METHODS: the expression levels of serum miR-21 and miR-210 in 40 CRC patients (CRC group) and 20 healthy patients (control group) were measured by qRT-PCR. Correlation analysis was performed of the relationship between serum miR-21 and miR-210 levels with clinical characteristics, including gender, age, tumor location, tumor size, tumor stage, local invasion and TNM staging. The expression levels of miR-21 and miR-210 in the CRC group were separately measured before and after surgery. ROC analysis was performed to evaluate the diagnostic value of miR-21 and miR-210. RESULTS: serum miR-21 and miR-210 in the CRC group were much higher than those in the control group. Meanwhile, the levels of serum miR-21 and miR-210 were closely related to tumor size (p = 0.028, p = 0.047), lymphatic metastasis (p = 0.038, p = 0.028), TNM staging (p = 0.014, p = 0.047) and tumor stage (p = 0.014, p = 0.017), but independent of gender, age and tumor location. In addition, serum miR-21 and miR-210 in the CRC group (n = 18) after surgery were lower than those before surgery (p < 0.001). ROC curves showed that miR-21 (AUC = 0.863) and miR-210 (AUC = 0.818) both had diagnostic efficacy in CRC patients. CONCLUSION: miR-21 and miR-210 can be used as novel non-invasive biomarkers for CRC diagnosis and prognosi


No disponible


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Neoplasias Colorretais/sangue , Neoplasias Colorretais/diagnóstico , MicroRNAs/sangue , Estudos de Casos e Controles , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Biomarcadores Tumorais/sangue , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real , Curva ROC , Valores de Referência , Fatores de Tempo
11.
Medicine (Baltimore) ; 99(43): e22803, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33120800

RESUMO

Routine postoperative surveillance is recommended for the patients with colorectal cancer (CRC). This study aimed to clarify the conditions indicate initial suspicion of CRC recurrence in different preoperative serum carcinoembryonic antigen (CEA) level groups, including positive physical signs/symptoms, elevated CEA level, positive radiologic studies results, and other elevated tumor markers.A total of 2268 patients with recurrence after curative surgery for CRC were enrolled in this study. The patients were classified into 3 groups according to preoperative serum CEA level (low, <2 ng/mL; intermediate, ≥2 and <5 ng/mL; and high, ≥5 ng/mL).Up to 63.6% of recurrence was suspected based on elevated CEA level in the high preoperative serum CEA level group. Patients in the low preoperative serum CEA level group had a higher rate of initial suspicion of recurrence based on positive physical signs or symptoms (36.7% vs 26.9% vs 20.4%, P < .001) and positive radiologic findings (51.4% vs 40.7% vs 29.5%, P < .001) than those in the intermediate and high preoperative serum CEA groups.Conditions indicate initial suspicion of recurrence varied in the different preoperative serum CEA level groups. In patients with low preoperative serum CEA level, the detection of recurrence depend on abnormal CEA level is less sensitive than intermediate and high preoperative serum CEA groups. We suggest that the strategy for CRC surveillance should not depend on serum CEA level alone. The signs or symptoms of patients, changes in postoperative serial CEA level, and ongoing radiologic or imaging findings must be cautiously monitored.


Assuntos
Antígeno Carcinoembrionário/sangue , Neoplasias Colorretais/patologia , Recidiva Local de Neoplasia/sangue , Idoso , Biomarcadores Tumorais , Neoplasias Colorretais/sangue , Neoplasias Colorretais/terapia , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
12.
Khirurgiia (Mosk) ; (10): 29-35, 2020.
Artigo em Russo | MEDLINE | ID: mdl-33047583

RESUMO

OBJECTIVE: To determine diagnostic value of neutrophil CD64 index (iCD64n) in the diagnosis of postoperative infectious complications after colorectal resections. MATERIAL AND METHODS: Seventy-three patients underwent colorectal surgery for the period from January to December 2018. These patients were included into a single-center study. Peripheral blood samples were taken on 3 and 6 postoperative days (POD) to check iCD64n level. We analyzed incidence of postoperative infectious complications, sensitivity (Se) and specificity (Sp) of postoperative iCD64n level on the 3rd and 6th POD. RESULTS: Postoperative infectious complications developed in 10 (13.7%) patients. Median iCD64n was significantly higher (p=0.0017 for POD 3; p=0.018 for POD 6) in patients with infectious complications (1.6 on POD 3; 1.3 on POD 6) compared to those without complications (1.1 on POD 3; 0.9 on POD 6). Area under curve (AUC) on the 3rd POD was 0.8 with the cut-off value of 1.4, Se - 70%, Sp - 93.7% (p=0.002). On the 6th POD, AUC was 0.91 with cut-off value of 1.23, Se - 80%, Sp - 93.7% (p<0.001). CONCLUSION: Neutrophil CD64 index is a valuable predictor for the diagnosis of postoperative infectious complications after colorectal resections. It is a useful tool to ensure a safe early discharge.The study is registered on the website «clinictrials.gov¼ (registration number NCT03559335).


Assuntos
Colectomia/efeitos adversos , Neoplasias Colorretais/sangue , Neoplasias Colorretais/cirurgia , Infecções/sangue , Infecções/diagnóstico , Receptores de IgG/sangue , Biomarcadores/sangue , Humanos , Infecções/etiologia , Infecções/imunologia , Neutrófilos/imunologia , Receptores de IgG/imunologia
13.
Life Sci ; 260: 118417, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32931801

RESUMO

AIMS: Colorectal cancer (CRC) is one of the most common cancers. However, the effective and non-invasive diagnostic biomarkers for the detection of CRC metastasis remain unsatisfied. Here, we aimed to evaluate the diagnostic performance of stool miR-135b-5p (a potential biomarker) for metastasis of CRC patients. MATERIALS AND METHODS: Serum and stool specimens from 77 patients with CRC and 29 normal controls were collected for miRNA purification. Real-time quantitative PCR was used for the relative quantification of miR-135b-5p expression. Receiver operating and characteristic (ROC) curve analysis was used to estimate the diagnostic performance of stool/serum miR-135b-5p for CRC metastasis. Dual-luciferase reporter assay was conducted to determine miR-135b-5p's target gene. Besides, a trans-well matrigel assay was performed to evaluate the invasion ability of HT-29 cell lines. KEY FINDINGS: Stool miR-135b-5p expression was dramatically up-regulated in CRC patients, and it effectively distinguished the CRC patients from normal controls with 74.1% of specificity and 96.5% of sensitivity. Moreover, stool miR-135b-5p exhibited a better diagnostic performance in distinguishing the different TNM stages of CRC patients than serum miR-135b-5p. In the molecular mechanism, our observations indicated that miR-135-5p directly targets the mRNA of ZNRF3, and then activates the Wnt pathway. Over-expression of ZNRF3 in HT-29 cells obviously reversed miR-135b-5p's effects on cell invasion and migration, indicating miR-135b-5p achieves its biological functions in a ZNRF3 dependent manner. SIGNIFICANCE: MiR-135b-5p may be a promising non-invasive biomarker for the diagnosis of CRC patients with TNM stage-III/IV and a potential candidate to develop an intervention strategy for colorectal cancer.


Assuntos
Biomarcadores Tumorais/genética , Movimento Celular , Neoplasias Colorretais/diagnóstico , Fezes/química , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Apoptose , Estudos de Casos e Controles , Proliferação de Células , Neoplasias Colorretais/sangue , Neoplasias Colorretais/genética , Humanos , Estadiamento de Neoplasias , Curva ROC , Células Tumorais Cultivadas
14.
J Cancer Res Clin Oncol ; 146(12): 3385-3388, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32857179

RESUMO

PURPOSE: Coronavirus disease 2019 (COVID-19) tends to affect multiple organs and induce abnormal laboratory parameters. We designed this study to investigate the association between carcinoembryonic antigen (CEA) elevation and SARS-CoV-2 infection. METHODS: We retrospectively analyzed 177 patients with confirmed SARS-CoV-2 infection who received plasma CEA assays during hospitalization. Patients with other causes of CEA elevation were excluded. Data regarding epidemiological and demographical characteristics, clinical symptoms, laboratory tests, and outcomes were analyzed. Linear regression analysis was used to evaluate the correlation between CEA levels and inflammation severity. RESULTS: 171 patients were included in the final study and 32 patients (18.7%) had raised serum of CEA (> 5 ng/ml), with a median (range) age of 66 (53-86). The median [interquartile range (IQR)] CEA level was 11.4 ng/ml (8.1-21.6), which was significantly higher than the upper limit of reference range. CEA level between 5-10 ng/ml was in 11 patients, 10-15 ng/ml in 10 patients, and > 15 ng/ml in 11 patients. No correlation was found between CEA levels and lymphocyte (R2 = 0.055; P = 0.10) nor CRP (R2 = 0.026; P = 0.38). The median levels of CEA were 20.0 ng/ml (IQR, 14.7-23.0) in non-survivors and 10.9 ng/ml (IQR 7.5-16.1) in survivors, and the difference between two groups was statistically significant (P = 0.048). CONCLUSION: SARS-CoV-2 infection might be another cause of CEA elevation, with nearly 20% of patients experienced transient and marked CEA increment during COVID-19 pneumonia. The false-positive results of CEA elevation might have clinical significance for patients with colorectal cancer.


Assuntos
Antígeno Carcinoembrionário/sangue , Neoplasias Colorretais/sangue , Infecções por Coronavirus/sangue , Pneumonia Viral/sangue , Pneumonia/sangue , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus/genética , Betacoronavirus/patogenicidade , Neoplasias Colorretais/complicações , Neoplasias Colorretais/patologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia/complicações , Pneumonia/patologia , Pneumonia Viral/complicações , Pneumonia Viral/patologia
15.
PLoS One ; 15(8): e0236569, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32756596

RESUMO

BACKGROUND: The inflammatory biomarkers, YKL-40 and interleukin-6 (IL-6), are elevated in patients with metastatic colorectal cancer. We examined their associations with relapse-free survival and overall survival in combination with serum C-reactive protein (CRP), carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9) in patients with colorectal liver metastases. METHODS: Altogether 441 consecutive patients undergoing liver resection at Helsinki University Hospital between 1998 and 2013 were included in the study. Pre- and postoperative YKL-40 and IL-6 were determined from serum samples with commercially available enzyme-linked immunosorbent assay (ELISA) kits, and CRP, CEA, and CA19-9 by routine methods. Associations between these biomarkers and relapse-free and overall survival were examined using Cox regression analysis. RESULTS: Patients with 2-5 elevated biomarkers were at an increased risk of relapse compared to those with 0-1 elevated biomarkers, preoperatively (HR 1.37, 95% CI 1.1-1.72) or postoperatively (HR 1.54, 95% CI 1.23-1.92). Patients with 2-5 elevated biomarkers were also at an increased risk of death compared to those with 0-1 elevated biomarkers, preoperatively (HR 1.76, 95% CI 1.39-2.24) or postoperatively (HR 1.83, 95% CI 1.44-2.33). CONCLUSION: The results suggest that a protein panel of the inflammatory biomarkers YKL-40, IL-6, and CRP, and the cancer biomarkers CEA and CA19-9 might identify patients that benefit from more aggressive treatment and surveillance, although the additional value of IL-6 and CRP in this aspect is limited.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Colorretais/sangue , Neoplasias Hepáticas/sangue , Recidiva Local de Neoplasia/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos Glicosídicos Associados a Tumores/sangue , Antígeno Carcinoembrionário/sangue , Proteína 1 Semelhante à Quitinase-3/sangue , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Feminino , Hepatectomia , Humanos , Interleucina-6/sangue , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Intervalo Livre de Progressão
16.
Life Sci ; 258: 118226, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32771555

RESUMO

AIM: Colorectal carcinoma (CRC) is one of the most prevalent cancers throughout the world. Circulating serum-derived microRNAs (miRNAs, miRs) can be used as non-invasive biomarkers for CRC diagnosis. This study aimed to identify a panel of six serum exosomal miRNAs as novel diagnostic biomarkers for CRC. MAIN METHODS: Exosomes were isolated and characterized from the conditioned media of the human colon adenocarcinoma cells (HCT-116 and Caco2). Sera were isolated from peripheral blood of 45 CRC and also 45 healthy individuals. The expression levels and diagnostic value of candidate circulating miRNAs (miR-19a, miR-20a, miR-150, miR-143, miR-145, and let-7a) were measured through quantitative real-time PCR. Receiver operating characteristic (ROC) curves were applied to evaluate the diagnostic accuracy of selected miRNAs. The association of candidate miRNAs and clinicopathological characteristics e.g. tumor node metastasis (TNM) staging and lymph node metastasis (LNM) were further evaluated. KEY FINDINGS: Circulating serum miR-19a, miR-20a, miR-150, and let-7a were significantly up-regulated in CRC patients, while miR-143 and miR-145 showed a significant down-regulation. The higher levels of miR-143 and miR-145 in patients with TNM stage I-II were detected, whereas miR-19a, miR-20a, miR-150, and let-7a were highly expressed in TNM stage III. The expression levels of miR-19a, miR-20a, and miR-150 were positively correlated with LNM status, while the expression levels of miR-143 and miR-145 were lower in patients with LNM. Area under the ROC curves of miR-19a, miR-20a, miR-150, miR-143, miR-145, and let-7a were 0.87, 0.83, 0.75, 0.76, 0.78 and 0.71, respectively. SIGNIFICANCE: We established a panel of six-circulating miRNA signature (i.e. miR-19a, miR-20a, miR-143, miR-145, miR-150, and let-7a) in serum as a non-invasive biomarker for CRC diagnosis. These findings confirm that serum-derived miRNAs have a strong potential to be a diagnostic biomarker for patients with CRC.


Assuntos
Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Neoplasias Colorretais/sangue , Neoplasias Colorretais/genética , MicroRNAs/sangue , MicroRNAs/genética , Adulto , Idoso , Células CACO-2 , Exossomos/genética , Exossomos/metabolismo , Feminino , Redes Reguladoras de Genes/genética , Células HCT116 , Humanos , Masculino , Pessoa de Meia-Idade
17.
Medicine (Baltimore) ; 99(28): e21171, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664155

RESUMO

BACKGROUND: Test on the KRAS somatic mutation status is necessary before cetuximab and panitumumab treatments are given to colorectal cancer patients. Metastatic colorectal cancer patients sometimes lack tumor tissue samples, and the testing of KRAS mutation in plasma samples requires highly sensitive methods. OBJECTIVES: The aim of this study was to evaluate the accuracy of digital PCR in detecting KRAS mutation in plasma samples of colorectal cancer patients. DATA SOURCES: Literature research was conducted in Pubmed, Embase, and Cochrane Library. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS: Database searching found 188 relevant studies. After removing duplicates, eligible studies were selected from 151 publications using the following exclusion criteria: STUDY APPRAISAL AND SYNTHESIS METHODS:: Data were extracted from the eligible studies by 2 independent researchers. Pooled accuracy parameters were calculated from those extracted data using Meta-DiSc and STATA software. RESULTS: Twelve eligible studies were selected for the systematic review and meta-analysis. After calculation, the pooled sensitivity and specificity were 0.83 (95% CI: 0.79-0.86) and 0.91 (95%CI: 0.88-0.93), respectively. Pooled positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 7.30 (95%CI: 4.78-11.17), 0.22 (95%CI: 0.15-0.32), and 41.00 (95%CI: 21.07-79.78), respectively. Area under curve of the summarized ROC curve was 0.9322. LIMITATIONS: Although no significant bias was identified, number of included studies was still quite small, especially in subgroup analysis. CONCLUSIONS AND IMPLICATION OF KEY FINDINGS: Digital PCR showed high accuracy and could be a reliable detection method for KRAS mutation in plasma samples. Large-cohort prospective study is required to further confirm the usefulness of digital PCR in KRAS mutation detection.


Assuntos
Neoplasias Colorretais/genética , Reação em Cadeia da Polimerase/estatística & dados numéricos , Proteínas Proto-Oncogênicas p21(ras)/genética , Adulto , Idoso , Neoplasias Colorretais/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Reação em Cadeia da Polimerase/métodos , Proteínas Proto-Oncogênicas p21(ras)/sangue , Curva ROC , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
18.
Medicine (Baltimore) ; 99(28): e21224, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664176

RESUMO

A great many circular RNAs (circRNAs) exist in different types of mammalian cells. Previous studies have verified that a low level of hsa_circ_0002320 is present in gastric cancer and that it might represent a good prognostic indicator. However, its value in colorectal cancer (CRC) is unclear. The aim of this research was to explore the value of hsa_circ_0002320 as a potential diagnostic biomarker for CRC prognosis.Plasma samples, CRC tissues, and adjacent normal tissues were obtained from 50 patients with CRC, before any treatment, and 100 plasma samples were acquired from healthy individuals. Hsa_circ_0002320 levels in these samples were analyzed by reverse transcription-quantitative polymerase chain reaction. Correlations between hsa_circ_0002320, clinicopathological characteristics, and overall survival (OS) of CRC patients were also investigated. Receiver-operating characteristic (ROC) curve analysis was used to assess the value of hsa_circ_0002320 for CRC diagnosis. Finally, a bioinformatics analysis was performed to verify the effect of hsa_circ_0002320 on CRC prognosis.Expression levels of hsa_circ_0002320 were significantly decreased in CRC plasma (P < .05). The expression level of hsa_circ_0002320 was significantly correlated with OS time (P < .05). Higher hsa_circ_0002320 reflected significantly greater OS; the HR of high hsa_circ_0002320 was 0.161 (95% CI, 0.066-0.393; P = .000). The area under the ROC curve of hsa_circ_0002320 in CRC was 0.823, which was higher than for the carcinoembryogenic antigen (area under the curve = 0.764). Kaplan-Meier analysis showed that CRC patients with low expression of hsa_circ_0002320 exhibited poorer OS times than those with high expression.Hsa_circ_0002320 could be a novel, noninvasive diagnostic blood biomarker for CRC prognosis.


Assuntos
Neoplasias Colorretais/sangue , Neoplasias Colorretais/mortalidade , RNA Circular/sangue , Biomarcadores Tumorais/sangue , Estudos de Casos e Controles , Neoplasias Colorretais/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Reação em Cadeia da Polimerase Via Transcriptase Reversa
19.
Ann Surg ; 272(2): 342-351, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32675548

RESUMO

BACKGROUND: Systemic inflammation via host-tumor interactions is currently recognized as a hallmark of cancer. The aim of this study was to evaluate the prognostic value of various combinations of inflammatory factors using preoperative blood, and to assess the clinical significance of our newly developed inflammatory score in colorectal cancer (CRC) patients. METHOD: In total 477 CRC patients from the discovery and validation cohorts were enrolled in this study. We assessed the predictive impact for recurrence using a combination of nine inflammatory markers in the discovery set, and focused on lymphocyte-C-reactive protein ratio (LCR) to elucidate its prognostic and predictive value for peri-operative risk in both cohorts. RESULTS: A combination of lymphocytic count along with C-reactive protein levels demonstrated the highest correlation with recurrence compared with other parameters in CRC patients. Lower levels of preoperative LCR significantly correlated with undifferentiated histology, advanced T stage, presence of lymph node metastasis, distant metastasis, and advanced stage classification. Decreased preoperative LCR (using an optimal cut-off threshold of 6000) was an independent prognostic factor for both disease-free survival and overall survival, and emerged as an independent risk factor for postoperative complications and surgical-site infections in CRC patients. Finally, we assessed the clinical feasibility of LCR in an independent validation cohort, and confirmed that decreased preoperative LCR was an independent prognostic factor for both disease-free survival and overall survival, and was an independent predictor for postoperative complications and surgical-site infections in CRC patients. CONCLUSION: Preoperative LCR is a useful marker for perioperative and postoperative management of CRC patients.


Assuntos
Biomarcadores Tumorais/sangue , Proteína C-Reativa/metabolismo , Neoplasias Colorretais/sangue , Neoplasias Colorretais/cirurgia , Linfócitos/metabolismo , Adulto , Idoso , Estudos de Coortes , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
20.
Gene ; 754: 144899, 2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-32544494

RESUMO

Epithelial-mesenchymal transition (EMT) plays a crucial role in colorectal cancer (CRC) metastasis. Soluble E-cadherin (sE-cadherin) is a peptide degradation product of the E-cadherin, a key epithelial molecule of EMT. However, it is not known if elevated levels of sE-cadherin also occur during EMT. And the study of sE-cadherin in colorectal cancer is rare. The purpose of the study was to evaluate the relationship between sE-cadherin and EMT in CRC and to evaluate the diagnostic value of sE-cadherin as a serum marker for CRC. Transforming growth factor-ß1 (TGF-ß1) was used to induce EMT in HT29 and SW480 cells. The cells treated with TGF-ß1 showed morphological and biological behavior changes consistent with EMT. Western blot and ELISA showed the levels of sE-cadherin were increased during EMT in CRC cells. In addition, we intravenously injected luciferase-labeled SW480 cells into nude mice to construct CRC metastasis model. Following the elongation of time, the fluorescence intensity of the experimental group was gradually increased. Correspondingly, the serum concentration of sE-cadherin also increased during CRC metastasis in mice. Furthermore, compared to healthy subjects, significantly higher levels of serum sE-cadherin were also observed in CRC patients and correlated with clinicopathological features. For discriminating CRC from healthy controls, the area under the receiver operating characteristic (ROC) curve (AUC) of sE-cadherin was 0.853, while the optimal cut-off point was set at 5928.16 ng/ml, the diagnostic sensitivity was 73.9% and the specificity was 80%. Compared with current commercial biomarkers (CEA, CA19-9 and CA125), the diagnostic performance of sE-cadherin was highest. Combined sE-cadherin and CEA raised the sensitivity to 82.4%. Serum sE-cadherin level can be used as a potential diagnostic biomarker of CRC.


Assuntos
Antígenos CD/sangue , Biomarcadores Tumorais/sangue , Caderinas/sangue , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/patologia , Transição Epitelial-Mesenquimal , Neoplasias Pulmonares/secundário , Animais , Apoptose , Neoplasias Colorretais/sangue , Feminino , Humanos , Neoplasias Pulmonares/sangue , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Prognóstico , Transdução de Sinais , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
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