Challenges for Triple Negative Breast Cancer Treatment: Defeating Heterogeneity and Cancer Stemness

Mahmoud, Rinad; Ordóñez‐Morán, Paloma; Allegrucci, Cinzia

doi:10.3390/cancers14174280

Cited by 29 publications

(21 citation statements)

References 104 publications

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“…Among other things, we did not include triple-negative BC in the study, which has an extremely unfavorable prognosis. However, triple-negative breast cancer, more often affects young women [ 56 ], and our cancer patients were postmenopausal. Nonetheless, we hope that our study will prove useful in the future in the biochemical diagnosis of not only BC of the Luminal A and Luminal B HER2-negative subtypes, but also other BC subtypes.…”

Section: Discussionmentioning

confidence: 99%

Plasma Levels of Metalloproteinase 3 (MMP-3) and Metalloproteinase 7 (MMP-7) as New Candidates for Tumor Biomarkers in Diagnostic of Breast Cancer Patients

Ławicki

Malinowski

Motyka

et al. 2023

JCM

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Matrix metalloproteinases (MMPs) are a group of enzymes that mediate both physiological and pathological processes such as carcinogenesis. The role of matrix metalloproteinase-3 (MMP-3) and (MMP-7) in the pathogenesis of breast cancer (BC) has been demonstrated, suggesting that they may be considered as potential markers of this condition. The aim of this study was to assess plasma concentrations and diagnostic utility of MMP-3 and MMP-7 in 100 patients with early-stage breast cancer with Luminal A subtype or Luminal B HER-negative subtype, before and after surgical treatment, and in the following control groups: patients with a benign tumor (fibroadenoma) and healthy subjects. The concentrations of MMP-3 and MMP-7 were referenced to the levels of the widely recognized marker for BC diagnosis CA 15-3. MMP-3 and MMP-7 was measured by ELISA method and CA 15-3 by CMIA. Plasma levels of MMP-7 were significantly higher in Luminal A and Luminal B HER2-negative subtype breast cancer patients as compared to the healthy group. MMP-7 demonstrated comparable but mostly higher to CA 15-3 or MMP-3 values of diagnostic sensitivity, specificity, positive and negative predictive values and AUC (0.6888 for Luminal A subtype; 0.7612 for Luminal B HER2-negative; 0.7250 for BC total group, respectively) in the groups tested. The combined use of the tested parameters resulted in a further increase in diagnostic criteria and AUC. These results suggest the usefulness of combining MMP-7 with CA 15-3 in the diagnostics of breast cancer, especially in Luminal B HER2-negative subtypes patients, as a new candidate for tumor markers.

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Section: Discussionmentioning

confidence: 99%

Plasma Levels of Metalloproteinase 3 (MMP-3) and Metalloproteinase 7 (MMP-7) as New Candidates for Tumor Biomarkers in Diagnostic of Breast Cancer Patients

Ławicki

Malinowski

Motyka

et al. 2023

JCM

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“…The stratification of breast cancer (BC) into morphologically and molecularly discrete subtypes has led to an overall improvement in treatment of patients with this disease [1,2]. TNBC, a subtype of BC with the poor prognosis is characterized by deficiency in expressions of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2).…”

Section: Introductionmentioning

confidence: 99%

“…TNBC accounts for approximately 10-15% of all BCs and is mostly common in women younger than 40 years, women of color or those with a BRCA1 mutation. TNBC differs from other types of invasive BC in that it tends to be more proliferative, highly metastatic, and has fewer therapeutic alternatives, therefore patients with this disease are inclined to have a worse prognosis [2][3][4].…”

Section: Introductionmentioning

confidence: 99%

Identification of a NACC1-Regulated Gene Signature Impli-Cated in the Features of Triple-Negative Breast Cancer

Liu¹,

Ngule²,

Hemati³

et al. 2023

Preprint

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Triple-negative breast cancer (TNBC), characterized by deficiency in estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor2 (HER2), is among the most lethal subtypes of breast cancer (BC). Nevertheless, the molecular determinants that contribute to its malignant phenotype such as tumor heterogeneity and therapy resistance remain elusive. In this study, we sought to identify the stemness-associated genes involved in TNBC progression. Using bioinformatics approach, we found 55-up and 9-down regulated genes in TNBC. Out of the 55 upregulated genes, a 5 gene-signature (CDK1, EZH2, CCNB1, CCNA2, and AURKA) involved in cell regeneration, was positively correlated with status of tumor hypoxia and clustered with stemness-associated genes, as recognized by Parametric Gene Set Enrichment Analysis (PGSEA). Also, enhanced infiltration of immunosuppressive cells was positively correlated with the expression of these 5 genes. Moreover, our experiments showed that depletion of the transcriptional co-factor nucleus accumbens-associated protein 1 (NAC1), which is highly expressed in TNBC, reduced the expressions of these genes. Thus, the five genes signature identified by this study warrants further exploration as a potential new biomarker of TNBC heterogeneity/stemness characterized by high hypoxia, stemness enrichment, and immune-suppressive tumor microenvironment.

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“…The stratification of breast cancer (BC) into morphologically and molecularly discrete subtypes has improved the overall treatment of patients with this disease [ 1 , 2 ]. TNBC, a subtype of BC with a poor prognosis is characterized by deficiency in the expressions of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2).…”

Section: Introductionmentioning

confidence: 99%

“…In addition, TNBC is more proliferative and metastatic, and there are few targeted therapies for TNBC. Therefore, patients with this disease are inclined to have a worse prognosis [ 2 , 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

Identification of a NACC1-Regulated Gene Signature Implicated in the Features of Triple-Negative Breast Cancer

et al. 2023

View full text Add to dashboard Cite

Triple-negative breast cancer (TNBC), characterized by a deficiency in estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor2 (HER2), is among the most lethal subtypes of breast cancer (BC). Nevertheless, the molecular determinants that contribute to its malignant phenotypes such as tumor heterogeneity and therapy resistance, remain elusive. In this study, we sought to identify the stemness-associated genes involved in TNBC progression. Using bioinformatics approaches, we found 55 up- and 9 downregulated genes in TNBC. Out of the 55 upregulated genes, a 5 gene-signature (CDK1, EZH2, CCNB1, CCNA2, and AURKA) involved in cell regeneration was positively correlated with the status of tumor hypoxia and clustered with stemness-associated genes, as recognized by Parametric Gene Set Enrichment Analysis (PGSEA). Enhanced infiltration of immunosuppressive cells was also positively correlated with the expression of these five genes. Moreover, our experiments showed that depletion of the transcriptional co-factor nucleus accumbens-associated protein 1 (NAC1), which is highly expressed in TNBC, reduced the expression of these genes. Thus, the five genes signature identified by this study warrants further exploration as a potential new biomarker of TNBC heterogeneity/stemness characterized by high hypoxia, stemness enrichment, and immune-suppressive tumor microenvironment.

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Challenges for Triple Negative Breast Cancer Treatment: Defeating Heterogeneity and Cancer Stemness

Cited by 29 publications

References 104 publications

Plasma Levels of Metalloproteinase 3 (MMP-3) and Metalloproteinase 7 (MMP-7) as New Candidates for Tumor Biomarkers in Diagnostic of Breast Cancer Patients

Plasma Levels of Metalloproteinase 3 (MMP-3) and Metalloproteinase 7 (MMP-7) as New Candidates for Tumor Biomarkers in Diagnostic of Breast Cancer Patients

Identification of a NACC1-Regulated Gene Signature Impli-Cated in the Features of Triple-Negative Breast Cancer

Identification of a NACC1-Regulated Gene Signature Implicated in the Features of Triple-Negative Breast Cancer

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