The Predictive Role of MMP-2, MMP-9, TIMP-1 and TIMP-2 Serum Levels in the Complete Response of the Tumor to Chemotherapy in Breast Cancer Patients

Özdemir, Kayhan; Zengin, İsmail; Eskiler, Gamze Güney; Koçer, Havva Belma; Özkan, Asuman Deveci; Demiray, Tayfur; Şahin, Elif

doi:10.1080/08941939.2022.2080308

Cited by 6 publications

(4 citation statements)

References 22 publications

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“…There were some reports examining the expression level of TIMP-2. In 2019, Wang and his colleagues reported significantly elevated transcriptional expression levels of TIMP-2 among tumor sites from 1097 BC cases compared to 114 normal controls, which conflicts with, yet holds greater persuasiveness in terms of sample size, than the findings presented by Ozdemir, which involved only 96 BC patients and 35 healthy individuals [19]. Furthermore, in 2022, Krasnikova and co-authors observed a notable decrease in serum TIMP-2 levels post-BC chemo-treatments among 67 BC patients compared with 25 healthy subjects [35].…”

Section: Discussionmentioning

confidence: 95%

“…A study by Peeney and his colleagues reported that TIMP-2 could suppress the growth metastasis of TNBC cells by modulating the epithelial-to-mesenchymal transition and naling pathways associated with metastatic outgrowth [18]. Subsequently, a 2022 s found significantly higher TIMP-2 expression among 96 BC patients compared t healthy individuals [19]. However, the precise contribution of elevated TIMP-2 to BC ology remains unclear.…”

Section: Introductionmentioning

confidence: 99%

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The Contribution of Tissue Inhibitor of Metalloproteinase-2 Genotypes to Breast Cancer Risk in Taiwan

Wang,

He,

Tsai

et al. 2023

Life

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Tissue inhibitor of metalloproteinase-2 (TIMP-2) is an endogenous inhibitor of matrix metalloproteinase-2 and is highly expressed in breast cancer (BC) cases at diagnosis. However, the genetic investigations for the association of TIMP-2 genotypes with BC risk are rather limited. In this study, contribution of TIMP-2 rs8179090, rs4789936, rs2009196 and rs7342880 genotypes to BC risk was examined among Taiwan’s BC population. TIMP-2 genotypic profiles were revealed among 1232 BC cases and 1232 controls about their contribution to BC using a PCR-based RFLP methodology. The TIMP-2 rs8179090 homozygous variant CC genotype was significantly higher in BC cases than controls (odds ratio (OR) = 2.76, 95% confidence interval (95%CI) = 1.78–4.28, p = 0.0001). Allelic analysis showed that C allele carriers have increased risk for BC (OR = 1.39, 95%CI = 1.20–1.62, p = 0.0001). Genotypic together with allelic analysis showed that TIMP-2 rs4789936, rs2009196 or rs7342880 were not associated with BC risk. Stratification analysis showed that TIMP-2 rs8179090 genotypes were significantly associated with BC risk among younger (≤55) aged women, not among those of an elder (>55) age. Last, rs8179090 genotypes were also associated with triple negative BC. This study sheds light into the etiology of BC in Taiwanese women. Rs8179090 may be incorporated into polygenic risk scores and risk prediction models, which could aid in stratifying individuals for targeted breast cancer screening.

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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

The Contribution of Tissue Inhibitor of Metalloproteinase-2 Genotypes to Breast Cancer Risk in Taiwan

Wang,

He,

Tsai

et al. 2023

Life

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“…The aberrant expression of a single DRG has been reported to associate with the therapeutic effects of chemotherapy ( 17 , 53 ), endocrinotherapy ( 54 ) and radiotherapy ( 55 , 56 ). In this study, the prognosis of patients undergoing endocrinotherapy or radiotherapy was worse in the high-risk group than in the low-risk group, possibly owing to treatment resistance induced by degradome dysfunction.…”

Section: Discussionmentioning

confidence: 99%

A degradome-based prognostic signature that correlates with immune infiltration and tumor mutation burden in breast cancer

Luo

Chen

et al. 2023

Front. Immunol.

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IntroductionFemale breast cancer is the most common malignancy worldwide, with a high disease burden. The degradome is the most abundant class of cellular enzymes that play an essential role in regulating cellular activity. Dysregulation of the degradome may disrupt cellular homeostasis and trigger carcinogenesis. Thus we attempted to understand the prognostic role of degradome in breast cancer by means of establishing a prognostic signature based on degradome-related genes (DRGs) and assessed its clinical utility in multiple dimensions.MethodsA total of 625 DRGs were obtained for analysis. Transcriptome data and clinical information of patients with breast cancer from TCGA-BRCA, METABRIC and GSE96058 were collected. NetworkAnalyst and cBioPortal were also utilized for analysis. LASSO regression analysis was employed to construct the degradome signature. Investigations of the degradome signature concerning clinical association, functional characterization, mutation landscape, immune infiltration, immune checkpoint expression and drug priority were orchestrated. Cell phenotype assays including colony formation, CCK8, transwell and wound healing were conducted in MCF-7 and MDA-MB-435S breast cancer cell lines, respectively.ResultsA 10-gene signature was developed and verified as an independent prognostic predictor combined with other clinicopathological parameters in breast cancer. The prognostic nomogram based on risk score (calculated based on the degradome signature) showed favourable capability in survival prediction and advantage in clinical benefit. High risk scores were associated with a higher degree of clinicopathological events (T4 stage and HER2-positive) and mutation frequency. Regulation of toll-like receptors and several cell cycle promoting activities were upregulated in the high-risk group. PIK3CA and TP53 mutations were dominant in the low- and high-risk groups, respectively. A significantly positive correlation was observed between the risk score and tumor mutation burden. The infiltration levels of immune cells and the expressions of immune checkpoints were significantly influenced by the risk score. Additionally, the degradome signature adequately predicted the survival of patients undergoing endocrinotherapy or radiotherapy. Patients in the low-risk group may achieve complete response after the first round of chemotherapy with cyclophosphamide and docetaxel, whereas patients in the high-risk group may benefit from 5-flfluorouracil. Several regulators of the PI3K/AKT/mTOR signaling pathway and the CDK family/PARP family were identified as potential molecular targets in the low- and high-risk groups, respectively. In vitro experiments further revealed that the knockdown of ABHD12 and USP41 significantly inhibit the proliferation, invasion and migration of breast cancer cells.ConclusionMultidimensional evaluation verified the clinical utility of the degradome signature in predicting prognosis, risk stratification and guiding treatment for patients with breast cancer.

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“…The acquisition of lower concentrations of MMP-2 and MMP-9 in patients with this bone cancer is surprising; however, it may indicate the potential of these compounds in the diagnosis and prognosis of OS patients. This requires continued research; however, it should be noted that the initial potential of these compounds as tumor markers has been demonstrated in the course of other conditions, such as ovarian [81], breast [82], and colorectal [83] cancers.…”

Section: Malignant Diseases Of Bone and Dental Cancers 421 Osteosarcomamentioning

confidence: 99%

Importance of Metalloproteinase Enzyme Group in Selected Skeletal System Diseases

Kulesza,

Kicman,

Motyka

et al. 2023

IJMS

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Bone tissue is a dynamic structure that is involved in maintaining the homeostasis of the body due to its multidirectional functions, such as its protective, endocrine, or immunological role. Specialized cells and the extracellular matrix (ECM) are responsible for the remodeling of specific bone structures, which alters the biomechanical properties of the tissue. Imbalances in bone-forming elements lead to the formation and progression of bone diseases. The most important family of enzymes responsible for bone ECM remodeling are matrix metalloproteinases (MMPs)—enzymes physiologically present in the body’s tissues and cells. The activity of MMPs is maintained in a state of balance; disruption of their activity is associated with the progression of many groups of diseases, including those of the skeletal system. This review summarizes the current understanding of the role of MMPs in bone physiology and the pathophysiology of bone tissue and describes their role in specific skeletal disorders. Additionally, this work collects data on the potential of MMPs as bio-markers for specific skeletal diseases.

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The Predictive Role of MMP-2, MMP-9, TIMP-1 and TIMP-2 Serum Levels in the Complete Response of the Tumor to Chemotherapy in Breast Cancer Patients

Cited by 6 publications

References 22 publications

The Contribution of Tissue Inhibitor of Metalloproteinase-2 Genotypes to Breast Cancer Risk in Taiwan

The Contribution of Tissue Inhibitor of Metalloproteinase-2 Genotypes to Breast Cancer Risk in Taiwan

A degradome-based prognostic signature that correlates with immune infiltration and tumor mutation burden in breast cancer

Importance of Metalloproteinase Enzyme Group in Selected Skeletal System Diseases

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