Serum levels of TIMP-1 and MMP-7 as potential biomarkers in patients with metastatic colorectal cancer

2019 ◽  
Vol 34 (3) ◽  
pp. 292-301 ◽  
Author(s):  
Michal Vočka ◽  
Daniel Langer ◽  
Vladimir Fryba ◽  
Jaromir Petrtyl ◽  
Tomas Hanus ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Carcinoembryonic Antigen ◽  
Serum Levels ◽  
Healthy Controls ◽  
Serum Samples ◽  
Gastrointestinal Malignancies ◽  
Matrix Metalloproteinase 7 ◽  
Growth Promoting ◽  
Potent Growth

Objective: Tissue inhibitor of metalloproteinases 1 (TIMP-1) and matrix metalloproteinase 7 (MMP-7) were reported to have potent growth promoting activity. Lack of balance between MMPs and TIMPs is an important factor in the development of gastrointestinal malignancies. Methods: We collected serum samples from 97 patients with metastatic colorectal cancer and 79 samples from healthy controls. Serum levels of TIMP-1 and MMP-7 were measured immunochemically and compared with standard tumor markers carcinoembryonic antigen and CA19-9. Results: Serum levels of TIMP-1 and MMP-7 were significantly higher in patients with colorectal cancer compared to healthy controls (both, P < 0.001). TIMP-1 and MMP-7 correlate with the presence of colon involvement (P = 0.001; P = 0.012) and the presence of liver metastases (P = 0.002; P = 0.037), and negatively correlate with pulmonary metastases (P = 0.014; P = 0.005). MMP-7 had similar sensitivity and the same specificity as carcinoembryonic antigen. TIMP-1 and MMP-7 had better sensitivity than CA19-9. TIMP-1 and MMP-7 level correlate with worse outcome (P = 0.002). Conclusion: The results indicate that TIMP-1 and MMP-7 are effective biomarkers in patients with metastatic colorectal cancer with good sensitivity. TIMP-1 and MMP-7 levels strongly correlate with the extent of liver disease and have prognostic value.

SDF-1 and VEGF-C as potential circulating angiogenic biomarkers for bevacizumab in patients with metastatic colorectal cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 480-480
Author(s):  
Mitsukuni Suenaga ◽  
Satoshi Matsusaka ◽  
Eiji Shinozaki ◽  
Mariko Ogura ◽  
Masato Ozaka ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Analysis Of Variance ◽  
Repeated Measures ◽  
Tumor Response ◽  
Serum Levels ◽  
Circulating Endothelial Cells ◽  
Continuous Variables ◽  
Serum Samples ◽  
Repeated Measures Analysis

480 Background: Bevacizumab (BV) plus chemotherapy (chemo) has been shown to improve survival for metastatic colorectal cancer (mCRC). Stromal cell-derived factor-1 (SDF-1) is known as a ligand for CXCR-4. We previously reported that proportion of CXCR4-positive circulating endothelial cells at baseline was correlated with the prognosis of BV plus chemo (Matsusaka, et al. Cancer. 2011). The aim of this study was to investigate changes during treatment in serum candidate cytokines including SDF-1 as potential markers of treatment response to BV. Methods: Patients receiving first-line BV plus chemo with mCRC were enrolled in this prospective study. Serum samples were analyzed before initiation of treatment and during treatment (on days 14 and 56) and at the time of progressive disease. Correlation between tumor response and changes in serum levels of the cytokines (such as VEGF, SDF-1, Ang-1 and -2, etc.) were investigated. Differences in the means of continuous measurements were tested by the Student’s t test. A two-way repeated-measures analysis of variance was used to evaluate differences between sequential continuous variables. Results: 24 were enrolled at the first interim analysis. 14 patients were assessable; some who got conversion surgery or discontinued treatment due to toxicity in early were excluded. Tumor response was achieved in 57% of the patients. SDF-1 levels at baseline (p=0.045) and on days 14 (p=0.049) were significantly lower in tumor responder, while a trend toward higher on days 56 compared to non-responder. The results of a two-way repeated-measures analysis of variance to evaluate differences between sequential continuous variables showed significant differences in VEGF-C (p=0.043) and SDF-1 (p=0.02), influenced by tumor response. Serum levels of SDF-1 trended toward increase on days 14 and decrease on days 56, whilst VEGF-C trended toward decrease on days 14 and 56. Conclusions: Changes Serum levels of SDF-1 and VEGF-C showed correlation with tumor response to BV plus chemo, suggesting that these surrogate markers may represent anti-angiogenic condition for BV treatment. This study is currently ongoing, and further analysis will be performed in more population.

scholarly journals Baseline carcinoembryonic antigen (CEA) serum levels predict bevacizumab‐based treatment response in metastatic colorectal cancer

2014 ◽  
Vol 105 (8) ◽  
pp. 996-1001 ◽  
Author(s):  
Gerald W. Prager ◽  
Kira H. Braemswig ◽  
Alexandra Martel ◽  
Matthias Unseld ◽  
Georg Heinze ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Carcinoembryonic Antigen ◽  
Treatment Response ◽  
Serum Levels

scholarly journals Quantitative Analysis of Methylated Adenosine Modifications Revealed Increased Levels of N6-Methyladenosine (m6A) and N6,2′-O-Dimethyladenosine (m6Am) in Serum From Colorectal Cancer and Gastric Cancer Patients

2021 ◽  
Vol 9 ◽  
Author(s):  
Yiqiu Hu ◽  
Zhihao Fang ◽  
Jiayi Mu ◽  
Yanqin Huang ◽  
Shu Zheng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gastric Cancer ◽  
Quantitative Analysis ◽  
Early Detection ◽  
Human Serum ◽  
Cancer Patients ◽  
Healthy Controls ◽  
Serum Samples ◽  
Gastrointestinal Malignancies ◽  
Gastric Cancer Patients

Colorectal cancer and gastric cancer are the most prevalent gastrointestinal malignancies worldwide, and early detection of these cancers is crucial to reduce their incidence and mortality. RNA methylation plays an important regulatory role in a variety of physiological activities, and it has drawn great attention in recent years. Methylated adenosine (A) modifications such as N6-methyladenosine (m6A), N1-methyladenosine (m1A), 2′-O-methyladenosine (Am), N6,2′-O-dimethyladenosine (m6Am), and N6,N6-dimethyladenosine (m62A) are typical epigenetic markers of RNA, and they are closely correlated to various diseases including cancer. Serum is a valuable source of biofluid for biomarker discovery, and determination of these adenosine modifications in human serum is desirable since they are emerging biomarkers for detection of diseases. In this work, a targeted quantitative analysis method using hydrophilic interaction liquid chromatography–tandem mass spectrometry (HILIC-MS/MS) was developed and utilized to analyze these methylated adenosine modifications in serum samples. The concentration differences between the healthy volunteers and cancer patients were evaluated by Mann–Whitney test, and receiver operator characteristic (ROC) curve analysis was performed to access the potential of these nucleosides as biomarkers. We demonstrated the presence of the m6Am in human serum for the first time, and we successfully quantified the concentrations of A, m6A, m1A, and m6Am in serum samples from 99 healthy controls, 51 colorectal cancer patients, and 27 gastric cancer patients. We found that the levels of m6A and m6Am in serum were both increased in colorectal cancer or gastric cancer patients, compared to that in healthy controls. These results indicate that m6A and m6Am in serum may act as potential biomarkers for early detection and prognosis of colorectal cancer and gastric cancer. In addition, the present work will stimulate investigations on the effects of adenosine methylation on the initiation and progression of colorectal cancer and gastric cancer.

scholarly journals Clinical and therapeutic features and prognostic factors of metastatic colorectal cancer over age 80: a retrospective study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hiroyuki Hisada ◽  
Yu Takahashi ◽  
Manabu Kubota ◽  
Haruhisa Shimura ◽  
Ei Itobayashi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Factors ◽  
Elderly Patients ◽  
Metastatic Colorectal Cancer ◽  
Carcinoembryonic Antigen ◽  
Prognostic Nutritional Index ◽  
Hazard Ratio ◽  
Elderly Group ◽  
Younger Patients ◽  
Nutritional Index

Abstract Background Colorectal cancer (CRC) is one of the most common cancers in the world. The number of elderly patients with CRC increases due to aging of the population. There are few studies that examined chemotherapy and prognostic factors in metastatic colorectal cancer (mCRC) patients aged ≥ 80 years. We assessed the efficacy of chemotherapy and prognostic factors among patients with mCRC aged ≥ 80 years. Methods We retrospectively analyzed clinical and laboratory findings of 987 patients newly diagnosed with CRC at Asahi General Hospital (Chiba, Japan) between January 2012 and December 2016. The Kaplan–Meier method was used for the overall survival (OS) and the log-rank test was used to identify difference between patients. A multivariate Cox proportional hazard regression analysis was performed to determine the hazard ratios and 95% confidence intervals (CIs) of prognostic factors among super-elderly patients. Results In total, 260 patients were diagnosed with mCRC (super-elderly group: n = 43, aged ≥ 80 years and younger group, n = 217, aged < 80 years). The performance status and nutritional status were worse in the super-elderly group than in the younger group. The OS of super-elderly patients who received chemotherapy was worse than that of younger patients (18.5 vs. 28.8 months; P = 0.052), although the difference was not significant. The OS of patients who received chemotherapy tended to be longer than that of those who did not; however, there were no significant differences in OS in the super-elderly group (18.5 vs. 8.4 months P = 0.33). Multivariate analysis revealed that carcinoembryonic antigen levels ≥ 5 ng/mL (hazard ratio: 2.27; 95% CI 1.09–4.74; P = 0.03) and prognostic nutritional index ≤ 35 (hazard ratio: 8.57; 95% CI 2.63–27.9; P = 0.0003) were independently associated with poor OS in the super-elderly group. Conclusions Patients with mCRC aged ≥ 80 years had lower OS than younger patients even though they received chemotherapy. Carcinoembryonic antigen and prognostic nutritional index were independent prognostic factors in super-elderly patients with mCRC, but chemotherapy was not. Trial registration: retrospectively registered.

scholarly journals Prognostic value of blood-based fibrosis biomarkers in patients with metastatic colorectal cancer receiving chemotherapy and bevacizumab

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Neel I. Nissen ◽  
Stephanie Kehlet ◽  
Mogens K. Boisen ◽  
Maria Liljefors ◽  
Christina Jensen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Collagen Type ◽  
Performance Status ◽  
Drug Uptake ◽  
Collagen Type Iii ◽  
Serum Samples ◽  
Type Iii ◽  
Poor Treatment ◽  
And Performance

AbstractA desmoplastic colorectal cancer stroma, characterized by excess turnover of the cancer-associated fibroblast derived collagens type III and VI, can lead to reduced drug-uptake and poor treatment response. We investigated the association between biomarkers of collagen type III and VI and overall survival (OS) in patients with metastatic colorectal cancer (mCRC). Serum samples were collected from 252 patients with mCRC prior to treatment with bevacizumab and chemotherapy. Serum concentrations of biomarkers reflecting formation of collagen type III (PRO-C3) and VI (PRO-C6) and degradation of collagen type VI (C6M and C6Mα3) were determined by ELISA. The biomarkers were evaluated for associations with OS, individually, combined, and after adjusting for carcinoembryonic antigen (CEA), lactate dehydrogenase (LDH) and performance status (PS). High baseline levels (> median) of each collagen biomarker were significantly associated with shorter OS (PRO-C3: HR = 2.0, 95%CI = 1.54–2.63; PRO-C6: HR = 1.6, 95%CI = 1.24–2.11; C6M: HR = 1.4, 95%CI = 1.05–1.78; C6Mα3: HR = 1.6, 95%CI = 1.16–2.07). PRO-C3 and PRO-C6 remained significant after adjustment for CEA, LDH and PS. Weak correlations were seen between the collagen biomarkers (r = 0.03–0.59) and combining all improved prognostic capacity (HR = 3.6, 95%CI = 2.30–5.76). Collagen biomarkers were predictive of shorter OS in patients with mCRC. This supports that collagen- and CAF biology is important in CRC.

scholarly journals Antibodies to Der p 1 and Der p 2 in allergic patients

2021 ◽  
Vol 49 (2) ◽  
pp. 46-52
Author(s):  
Renata Harumi Cruz ◽  
Leandro Hideki Ynoue ◽  
Carolina Sanchez Aranda ◽  
Dirceu Solé ◽  
Antonio Condino Neto
Keyword(s):  
Serum Levels ◽  
Specific Ige ◽  
Protective Mechanism ◽  
Healthy Controls ◽  
Healthy Individuals ◽  
Serum Samples ◽  
Th2 Response ◽  
Iga Antibodies ◽  
Der P 1 ◽  
Der P 2

Introduction and objectives: Atopic individuals are characterized by increased IgE production and Th2 response if exposed to certain antigens. It is known that the mother transfers antimite antibodies to the fetus and newborn, IgG thru the placenta, and IgA thru breastfeeding, but it is not clear whether there is a protective mechanism mediated by them concerning the development of future allergies. This study aimed to compare the levels of IgA, IgG, and IgE antibodies specific to Der p 1 and Der p 2 between atopic and healthy individuals.Methods: Serum samples of 98 patients and 44 healthy controls were subjected to quantification for specific IgE, IgG, and IgA antibodies against Der p 1 and Der p 2 by ImmunoCap® and ELISA, and subjected to statistical analysis as indicated.Results: Atopic patients had higher serum levels of IgE, IgG, and IgA specific to Der p 1 and Der p 2. The correlation was more robust between IgE and IgG antibodies.Conclusions: Allergic patients produce higher levels of antibodies against Der p 1 and Der p 2 compared with healthy individuals. The mechanisms involved still require detailed studies.

scholarly journals Serum Levels of BDNF in Patients with Adenoma and Colorectal Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Zhe Wang ◽  
Shuang Wang ◽  
Yu Liu ◽  
Shan Gao ◽  
Yunqing Yu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Diagnostic Performance ◽  
Serum Levels ◽  
Tnm Staging ◽  
Laboratory Method ◽  
Healthy Controls ◽  
Tumor Differentiation ◽  
Combined Detection ◽  
Control Study ◽  
Serum Bdnf

The present study is aimed at examining the serum levels of brain-derived neurotrophic factor (BDNF) and investigating its role in differential diagnosis of colorectal cancer (CRC). Materials and Methods. In a Chinese population, we conducted a case-control study to compare the diagnostic performance of serum levels of BDNF and carcinoembryonic antigen (CEA) for CRC. We enrolled 61 healthy controls, 31 patients with adenomas, and 81 patients with CRC. We explored the correlation between serum levels of BDNF and several pathological features, such as tumor differentiation and TNM staging. Results. The serum levels of BDNF were significantly ( p < 0.0001 ) higher in patients with CRC ( 10.64 ± 3.84 , n = 81 ) than in the healthy controls ( 4.69 ± 1.69   ng / mL , n = 61 ). Serum BDNF also correlated with tumor size, tumor differentiation, and TNM staging ( p < 0.05 ). For early diagnosis, the combination of BDNF (AUC 0.719; 95% CI, 0.621–0.816) and CEA (AUC 0.733; 95% CI, 0.632–0.909) slightly improved the diagnostic performance for CRC (AUC 0.823; 95% CI, 0.737-0.909). Conclusions. Combined detection of serum BDNF and CEA may thus have the potential to become a new laboratory method for the early clinical diagnosis of CRC.

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