The prognostic significance of interferon-stimulated gene 15 (ISG15) in invasive breast cancer

Abstract Background Lymphovascular invasion (LVI) is a prognostic factor in early-stage invasive breast cancer (BC). Through bioinformatics, data analyses of multiple BC cohorts revealed the positive association between interferon-stimulated gene 15 (ISG15) LVI status. Thus, we explored the prognostic significance of ISG15 in BC. Methods The prognostic significance of ISG15 mRNA was assessed in METABRIC (n = 1980), TCGA (n = 854) and Kaplan–Meier Plotter (n = 3951). ISG15 protein was evaluated using immunohistochemistry (n = 859) in early-stage invasive BC patients with long-term follow-up. The associations between ISG15 expression and clinicopathological features, expression of immune cell markers and patient outcome data were evaluated. Results High mRNA and protein ISG15 expression were associated with LVI, higher histological grade, larger tumour size, hormonal receptor negativity, HER2 positivity, p53 and Ki67. High ISG15 protein expression was associated with HER2-enriched BC subtypes and immune markers (CD8, FOXP3 and CD68). High ISG15 mRNA and ISG15 expressions were associated with poor patient outcome. Cox proportional multivariate analysis revealed that the elevated ISG15 expression was an independent prognostic factor of shorter BC-specific survival. Conclusion This study provides evidence for the role of ISG15 in LVI development and BC prognosis. Further functional studies in BC are warranted to evaluate the therapeutic potential of ISG15.

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Body Mass Index at Diagnosis as a Prognostic Factor for Early-Stage Invasive Breast Cancer after Surgical Resection

Oncology Research and Treatment ◽

10.1159/000496548 ◽

2019 ◽

Vol 42 (4) ◽

pp. 195-201 ◽

Cited By ~ 2

Author(s):

Xue Wang ◽

Tian-Li Hui ◽

Mei-Qi Wang ◽

Huan Liu ◽

Ruo-Yang Li ◽

...

Keyword(s):

Breast Cancer ◽

Body Mass Index ◽

Prognostic Factor ◽

Surgical Resection ◽

Body Mass ◽

Invasive Breast Cancer ◽

Early Stage

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Tumour-Infiltrating Inflammatory Cells in Early Breast Cancer: An Underrated Prognostic and Predictive Factor?

International Journal of Molecular Sciences ◽

10.3390/ijms21218238 ◽

2020 ◽

Vol 21 (21) ◽

pp. 8238

Author(s):

Sören Schnellhardt ◽

Ramona Erber ◽

Maike Büttner-Herold ◽

Marie-Charlotte Rosahl ◽

Oliver J. Ott ◽

...

Keyword(s):

Breast Cancer ◽

Disease Progression ◽

Immune Cell ◽

Early Stage ◽

Prognostic Significance ◽

Disease Free Survival ◽

Inflammatory Cells ◽

Accelerated Partial Breast Irradiation ◽

Partial Breast Irradiation ◽

Tumour Resection

The role of tumour-infiltrating inflammatory cells (TIICs) in the disease progression of hormone-receptor-positive breast cancer (HR+ BC) is largely unclear since it is generally regarded as the least immunogenic BC subtype. This study investigated the prognostic significance of CD1a+ dendritic cells, CD20+ B cells, CD45RO+ memory T cells and CD4+ T-helper cells in HR+ BC. One hundred and forty-six patients were treated for early stage, distant-metastases-free HR+ BC in an accelerated partial breast irradiation (APBI) phase II trial. Immunohistochemistry was used to double-stain two adjoining sets of tissue microarrays from pre-RT (radiotherapy) tumour resection samples for CD1a/CD20 and CD45RO/CD4. Cell densities of CD1a+, CD20+, CD45RO+ and CD4+ TIICs in the stromal and intraepithelial compartment were registered semiautomatically. High densities of CD20+ and CD4+ TIICs were strongly associated with reduced disease-free survival (DFS), while high stromal CD45RO+ TIIC densities were indicators of subsequent successful treatment. An immunoscore based on CD20+ and CD45RO+ TIIC densities identified three different risk groups (p < 0.001). Thus, contrary to current assumptions, intratumoural immune cell composition might be an important prognostic indicator and a possible contributing factor in the outcome of HR+ BC and should be the subject of further research. Specifically, B-cell infiltration entailed an increased relapse rate and could play an important role in disease progression.

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Estrogen-Dependent Prognostic Significance of COX-2 in Early Stage Invasive Breast Cancer

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2007.07.048 ◽

2007 ◽

Vol 69 (3) ◽

pp. S27

Author(s):

B.G. Haffty ◽

M.S. Moran ◽

Q. Yang ◽

A. Tan ◽

M. Reiss

Keyword(s):

Breast Cancer ◽

Invasive Breast Cancer ◽

Early Stage ◽

Prognostic Significance ◽

Cox 2

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Prospective Randomized Trial of Use of In-House Prepared Low-Cost Radiopharmaceutical Versus Commercial Radiopharmaceutical for Sentinel Lymph Node Biopsy in Patients with Early Stage Invasive Breast Cancer

World Journal of Surgery ◽

10.1007/s00268-018-4504-2 ◽

2018 ◽

Vol 42 (5) ◽

pp. 1391-1395

Author(s):

Gaurav Agarwal ◽

Sendhil Rajan ◽

Sabaretnam Mayilvaganan ◽

Anjali Mishra ◽

Narendra Krishnani ◽

...

Keyword(s):

Breast Cancer ◽

Lymph Node ◽

Sentinel Lymph Node ◽

Sentinel Lymph Node Biopsy ◽

Randomized Trial ◽

Invasive Breast Cancer ◽

Early Stage ◽

Low Cost ◽

Lymph Node Biopsy ◽

Node Biopsy

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Stromal Cell-Derived Factor 1α (SDF-1α) in Invasive Breast Cancer: Associations with Vasculo-Angiogenic Factors and Prognostic Significance

Cancers ◽

10.3390/cancers13081952 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1952

Author(s):

Elżbieta Zarychta ◽

Barbara Ruszkowska-Ciastek ◽

Kornel Bielawski ◽

Piotr Rhone

Keyword(s):

Breast Cancer ◽

Invasive Breast Cancer ◽

Stromal Cell ◽

Prognostic Significance ◽

Disease Free Survival ◽

Breast Cancer Patients ◽

Roc Curve Analysis ◽

Stromal Cell Derived Factor ◽

A Prospective Study

(1) Background: Tumour angiogenesis is critical for the progression of neoplasms. A prospective study was designed to examine the utility of stromal cell-derived factor 1α (SDF-1α) and selected vasculo-angiogenic parameters for estimating the probability of disease relapse in 84 primary, operable invasive breast cancer (IBrC) patients (40 (48%) with stage IA and 44 (52%) with stage IIA and IIB). (2) Methods: We explored the prognostic value of the plasma levels of SDF-1α, vascular endothelial growth factor A (VEGF-A), the soluble forms of VEGF receptors type 1 and 2, and the number of circulating endothelial progenitor cells (circulating EPCs) in breast cancer patients. The median follow-up duration was 58 months, with complete follow-up for the first event. (3) Results: According to ROC curve analysis, the optimal cut-off point for SDF-1α (for discriminating between patients at high and low risk of relapse) was 42 pg/mL, providing 57% sensitivity and 75% specificity. Kaplan–Meier curves for disease-free survival (DFS) showed that concentrations of SDF-1α lower than 42 pg/dL together with a VEGFR1 lower than 29.86 pg/mL were significantly associated with shorter DFS in IBrC patients (p = 0.0381). Patients with both SDF-1α lower than 42 pg/dL and a number of circulating EPCs lower than 9.68 cells/µL had significantly shorter DFS (p = 0.0138). (4) Conclusions: Our results imply the clinical usefulness of SDF-1α, sVEGFR1 and the number of circulating EPCs as prognostic markers for breast cancer in clinical settings.

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The Biological and Clinical Significance of Glutaminase in Luminal Breast Cancer

Cancers ◽

10.3390/cancers13163963 ◽

2021 ◽

Vol 13 (16) ◽

pp. 3963

Author(s):

Brendah K. Masisi ◽

Rokaya El Ansari ◽

Lutfi Alfarsi ◽

Madeleine L. Craze ◽

Natasha Jewa ◽

...

Keyword(s):

Breast Cancer ◽

Patient Outcome ◽

Ductal Carcinoma ◽

Tumour Size ◽

Prognostic Significance ◽

Disease Free Survival ◽

Glutamine Metabolism ◽

Gene Copy ◽

Luminal Breast Cancer ◽

Potential Biomarker

The glutamine metabolism has a key role in the regulation of uncontrolled tumour growth. This study aimed to evaluate the expression and prognostic significance of glutaminase in luminal breast cancer (BC). The glutaminase isoforms (GLS/GLS2) were assessed at genomic/transcriptomic levels, using METABRIC (n = 1398) and GeneMiner datasets (n = 4712), and protein using immunohistochemistry in well-characterised cohorts of Oestrogen receptor-positive/HER2-negative BC patients: ductal carcinoma in situ (DCIS; n = 206) and invasive breast cancer (IBC; n = 717). Glutaminase expression was associated with clinicopathological features, patient outcome and glutamine-metabolism-related genes. In DCIS, GLS alone and GLS+/GLS2- expression were risk factors for shorter local recurrence-free interval (p < 0.0001 and p = 0.001, respectively) and remained prognostic factors independent of tumour size, grade and comedo necrosis (p = 0.0008 and p = 0.003, respectively). In IBC, GLS gene copy number gain with high mRNA expression was associated with poor patient outcome (p = 0.011), whereas high GLS2 protein was predictive of a longer disease-free survival (p = 0.006). Glutaminase plays a role in the biological function of luminal BC, particularly GLS in the early non-invasive stage, which could be used as a potential biomarker to predict disease progression and a target for inhibition. Further validation is required to confirm these observations, and functional assessments are needed to explore their specific roles.

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