Serum MMP-8 and TIMP-1 as prognostic biomarkers in gastric cancer

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

Kuvaus

Despite gastric cancer being rare nowadays in Western countries, it remains one of the leading causes of cancer death worldwide. The course of the disease varies, so the individual gastric cancer patient’s prognosis is difficult to determine. The need for new biomarkers is crucial. The aim of this study was to evaluate the prognostic value of serum matrix metalloproteinase-8, serum tissue inhibitor of metalloproteinase-1, and tissue matrix metalloproteinase-8 in patients with gastric cancer. Preoperative serum samples from 233 patients with gastric cancer were retrospectively analyzed. Serum levels of matrix metalloproteinase-8 were analyzed with immunofluorometric assay, and tissue inhibitor of metalloproteinase-1 levels were determined by enzyme-linked immunosorbent assay. We also determined the tissue expression of matrix metalloproteinase-8 in 276 gastric cancer samples by immunohistochemistry. Survival data and death causes came from patient records, the Population Register Center of Finland, and Statistics Finland. Patients with a low (131 ng/mL) serum matrix metalloproteinase-8 level had a considerably unfavorable prognosis (p = 0.002). Those patients with a high (≥170 ng/mL) serum tissue inhibitor of metalloproteinase-1 level also had a poor prognosis (p <0.001), and the latter remained significant in multivariable analysis (hazard ratio = 1.85; 95% confidence interval: 1.26–2.72; p = 0.002). The molar ratio of serum matrix metalloproteinase-8 and tissue inhibitor of metalloproteinase-1 levels with low (0.30) molar ratios predicted a worse prognosis (p = 0.020). Tissue matrix metalloproteinase-8 did not influence prognosis. These results suggest that serum matrix metalloproteinase-8, tissue inhibitor of metalloproteinase-1, and the ratio of matrix metalloproteinase-8/ tissue inhibitor of metalloproteinase-1 may prove useful biomarkers for prediction of prognosis in patients with gastric cancer. © The Author(s) 2018.
Alkuperäiskielienglanti
LehtiTumor Biology
Vuosikerta40
Numero9
ISSN1010-4283
DOI - pysyväislinkit
TilaJulkaistu - 2018
OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu

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title = "Serum MMP-8 and TIMP-1 as prognostic biomarkers in gastric cancer",
abstract = "Despite gastric cancer being rare nowadays in Western countries, it remains one of the leading causes of cancer death worldwide. The course of the disease varies, so the individual gastric cancer patient’s prognosis is difficult to determine. The need for new biomarkers is crucial. The aim of this study was to evaluate the prognostic value of serum matrix metalloproteinase-8, serum tissue inhibitor of metalloproteinase-1, and tissue matrix metalloproteinase-8 in patients with gastric cancer. Preoperative serum samples from 233 patients with gastric cancer were retrospectively analyzed. Serum levels of matrix metalloproteinase-8 were analyzed with immunofluorometric assay, and tissue inhibitor of metalloproteinase-1 levels were determined by enzyme-linked immunosorbent assay. We also determined the tissue expression of matrix metalloproteinase-8 in 276 gastric cancer samples by immunohistochemistry. Survival data and death causes came from patient records, the Population Register Center of Finland, and Statistics Finland. Patients with a low (131 ng/mL) serum matrix metalloproteinase-8 level had a considerably unfavorable prognosis (p = 0.002). Those patients with a high (≥170 ng/mL) serum tissue inhibitor of metalloproteinase-1 level also had a poor prognosis (p <0.001), and the latter remained significant in multivariable analysis (hazard ratio = 1.85; 95{\%} confidence interval: 1.26–2.72; p = 0.002). The molar ratio of serum matrix metalloproteinase-8 and tissue inhibitor of metalloproteinase-1 levels with low (0.30) molar ratios predicted a worse prognosis (p = 0.020). Tissue matrix metalloproteinase-8 did not influence prognosis. These results suggest that serum matrix metalloproteinase-8, tissue inhibitor of metalloproteinase-1, and the ratio of matrix metalloproteinase-8/ tissue inhibitor of metalloproteinase-1 may prove useful biomarkers for prediction of prognosis in patients with gastric cancer. {\circledC} The Author(s) 2018.",
keywords = "neutrophil collagenase, tissue inhibitor of metalloproteinase 1, MMP8 protein, human, TIMP1 protein, human, tumor marker, adult, aged, Article, blood sampling, cancer mortality, cancer prognosis, cancer survival, cohort analysis, controlled study, enzyme linked immunosorbent assay, female, Finland, human, human cell, human tissue, immunofluorescence test, immunohistochemistry, major clinical study, male, medical record, prediction, preoperative evaluation, priority journal, protein blood level, protein expression, retrospective study, stomach cancer, adenocarcinoma, blood, follow up, lymph node metastasis, middle aged, pathology, prognosis, secondary, stomach tumor, survival rate, tumor invasion, Adenocarcinoma, Aged, Biomarkers, Tumor, Female, Follow-Up Studies, Humans, Lymphatic Metastasis, Male, Matrix Metalloproteinase 8, Middle Aged, Neoplasm Invasiveness, Prognosis, Retrospective Studies, Stomach Neoplasms, Survival Rate, Tissue Inhibitor of Metalloproteinase-1, 3122 Cancers",
author = "A. Laitinen and J. Hagstr{\"o}m and H. Mustonen and A. Kokkola and T. Tervahartiala and T. Sorsa and C. B{\"o}ckelman and C. Haglund",
year = "2018",
doi = "10.1177/1010428318799266",
language = "English",
volume = "40",
journal = "Tumor Biology",
issn = "1010-4283",
publisher = "SAGE Publications Ltd STM",
number = "9",

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Serum MMP-8 and TIMP-1 as prognostic biomarkers in gastric cancer. / Laitinen, A.; Hagström, J.; Mustonen, H.; Kokkola, A.; Tervahartiala, T.; Sorsa, T.; Böckelman, C.; Haglund, C.

julkaisussa: Tumor Biology, Vuosikerta 40, Nro 9, 2018.

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

TY - JOUR

T1 - Serum MMP-8 and TIMP-1 as prognostic biomarkers in gastric cancer

AU - Laitinen, A.

AU - Hagström, J.

AU - Mustonen, H.

AU - Kokkola, A.

AU - Tervahartiala, T.

AU - Sorsa, T.

AU - Böckelman, C.

AU - Haglund, C.

PY - 2018

Y1 - 2018

N2 - Despite gastric cancer being rare nowadays in Western countries, it remains one of the leading causes of cancer death worldwide. The course of the disease varies, so the individual gastric cancer patient’s prognosis is difficult to determine. The need for new biomarkers is crucial. The aim of this study was to evaluate the prognostic value of serum matrix metalloproteinase-8, serum tissue inhibitor of metalloproteinase-1, and tissue matrix metalloproteinase-8 in patients with gastric cancer. Preoperative serum samples from 233 patients with gastric cancer were retrospectively analyzed. Serum levels of matrix metalloproteinase-8 were analyzed with immunofluorometric assay, and tissue inhibitor of metalloproteinase-1 levels were determined by enzyme-linked immunosorbent assay. We also determined the tissue expression of matrix metalloproteinase-8 in 276 gastric cancer samples by immunohistochemistry. Survival data and death causes came from patient records, the Population Register Center of Finland, and Statistics Finland. Patients with a low (131 ng/mL) serum matrix metalloproteinase-8 level had a considerably unfavorable prognosis (p = 0.002). Those patients with a high (≥170 ng/mL) serum tissue inhibitor of metalloproteinase-1 level also had a poor prognosis (p <0.001), and the latter remained significant in multivariable analysis (hazard ratio = 1.85; 95% confidence interval: 1.26–2.72; p = 0.002). The molar ratio of serum matrix metalloproteinase-8 and tissue inhibitor of metalloproteinase-1 levels with low (0.30) molar ratios predicted a worse prognosis (p = 0.020). Tissue matrix metalloproteinase-8 did not influence prognosis. These results suggest that serum matrix metalloproteinase-8, tissue inhibitor of metalloproteinase-1, and the ratio of matrix metalloproteinase-8/ tissue inhibitor of metalloproteinase-1 may prove useful biomarkers for prediction of prognosis in patients with gastric cancer. © The Author(s) 2018.

AB - Despite gastric cancer being rare nowadays in Western countries, it remains one of the leading causes of cancer death worldwide. The course of the disease varies, so the individual gastric cancer patient’s prognosis is difficult to determine. The need for new biomarkers is crucial. The aim of this study was to evaluate the prognostic value of serum matrix metalloproteinase-8, serum tissue inhibitor of metalloproteinase-1, and tissue matrix metalloproteinase-8 in patients with gastric cancer. Preoperative serum samples from 233 patients with gastric cancer were retrospectively analyzed. Serum levels of matrix metalloproteinase-8 were analyzed with immunofluorometric assay, and tissue inhibitor of metalloproteinase-1 levels were determined by enzyme-linked immunosorbent assay. We also determined the tissue expression of matrix metalloproteinase-8 in 276 gastric cancer samples by immunohistochemistry. Survival data and death causes came from patient records, the Population Register Center of Finland, and Statistics Finland. Patients with a low (131 ng/mL) serum matrix metalloproteinase-8 level had a considerably unfavorable prognosis (p = 0.002). Those patients with a high (≥170 ng/mL) serum tissue inhibitor of metalloproteinase-1 level also had a poor prognosis (p <0.001), and the latter remained significant in multivariable analysis (hazard ratio = 1.85; 95% confidence interval: 1.26–2.72; p = 0.002). The molar ratio of serum matrix metalloproteinase-8 and tissue inhibitor of metalloproteinase-1 levels with low (0.30) molar ratios predicted a worse prognosis (p = 0.020). Tissue matrix metalloproteinase-8 did not influence prognosis. These results suggest that serum matrix metalloproteinase-8, tissue inhibitor of metalloproteinase-1, and the ratio of matrix metalloproteinase-8/ tissue inhibitor of metalloproteinase-1 may prove useful biomarkers for prediction of prognosis in patients with gastric cancer. © The Author(s) 2018.

KW - neutrophil collagenase

KW - tissue inhibitor of metalloproteinase 1

KW - MMP8 protein, human

KW - TIMP1 protein, human

KW - tumor marker, adult

KW - aged

KW - Article

KW - blood sampling

KW - cancer mortality

KW - cancer prognosis

KW - cancer survival

KW - cohort analysis

KW - controlled study

KW - enzyme linked immunosorbent assay

KW - female

KW - Finland

KW - human

KW - human cell

KW - human tissue

KW - immunofluorescence test

KW - immunohistochemistry

KW - major clinical study

KW - male

KW - medical record

KW - prediction

KW - preoperative evaluation

KW - priority journal

KW - protein blood level

KW - protein expression

KW - retrospective study

KW - stomach cancer

KW - adenocarcinoma

KW - blood

KW - follow up

KW - lymph node metastasis

KW - middle aged

KW - pathology

KW - prognosis

KW - secondary

KW - stomach tumor

KW - survival rate

KW - tumor invasion, Adenocarcinoma

KW - Aged

KW - Biomarkers, Tumor

KW - Female

KW - Follow-Up Studies

KW - Humans

KW - Lymphatic Metastasis

KW - Male

KW - Matrix Metalloproteinase 8

KW - Middle Aged

KW - Neoplasm Invasiveness

KW - Prognosis

KW - Retrospective Studies

KW - Stomach Neoplasms

KW - Survival Rate

KW - Tissue Inhibitor of Metalloproteinase-1

KW - 3122 Cancers

U2 - 10.1177/1010428318799266

DO - 10.1177/1010428318799266

M3 - Article

VL - 40

JO - Tumor Biology

JF - Tumor Biology

SN - 1010-4283

IS - 9

ER -