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Cited by 150Breast Cancer Treatment StudiesChemokine receptors and signalingBreast Lesions and Carcinomas

Evaluation of invasive breast cancer samples using a 12-chemokine gene expression score: correlation with clinical outcomes

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Prabhakaran, Sangeetha, Rizk, Victoria T., Ma, Zhenjun, Cheng, Chia-Ho, Berglund, Anders E., Coppola, Dominico, Khalil, Farah, Mulé, James J. +1 more·2017·Breast Cancer Research
DOI 10.1186/s13058-017-0864-zPMC PMC5477261
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Abstract

BACKGROUND: A unique 12-chemokine gene expression score (CS) accurately predicted the presence of tumor-localized, ectopic lymph node-like structures (TL-ELNs) and improved overall survival (OS) in primary colorectal cancer and metastatic melanoma. We analyzed the correlation between CS, clinicopathological variables, molecular data, and 366 survival in Moffitt Cancer Center's Total Cancer Care (TCC) patients with non-metastatic breast cancer. METHODS: Affymetrix gene expression profiles were used to interrogate the CS by the principal component method. Breast tumors were classified as high or low score based on median split, and correlations between clinicopathologic variables, PAM50 molecular subtype, and ELN formation were analyzed using the TCC dataset. Differences in overall survival (OS) and recurrence-free survival (RFS) in the larger KM Plot breast cancer public datasets were compared using Kaplan-Meier curves. RESULTS: We divided the Total Cancer Care (TCC) breast cancer patients into two groups of high or low CS. Mean CS was 0.24 (range, 2.2-2.1). Patients with higher CS were more likely to be white (172 vs. 159; p = 0.03), had poorly differentiated tumors (112 vs. 59; p <0.0001), ER/PR negative (41 vs. 26) and HER2 positive (36 vs. 19; p = 0.001), and contain TL-ELNs. Higher CS scores were also seen in the basal and HER2+ molecular subtypes. In the KM Plot breast cancer datasets higher CS patients demonstrated superior OS (HR = 0.73, p = 0.008) and RFS (HR 0.76, p = <0.0001), especially in basal and HER2+ patients. CONCLUSIONS: High CS breast tumors tend to be higher grade, basal or HER2+, and present more frequently in Caucasians. However, this group of patients also shows the presence of TL-ELNs within the tumor microenvironment and has better survival outcomes. The CS is a novel tool that can identify breast cancer patients with tumors of a unique intratumoral immune composition and better prognosis. Whether or not the CS is a predictive response marker in breast cancer patients undergoing immunotherapy remains to be determined.

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  • CXCL10 expression has been correlated with the presence of tumor-associated tertiary lymphoid structures.

    “Also, as a member of the 12-chemokine gene signature classifier33, its expression has been correlated with the presence of tumor-associated tertiary lymphoid structures50–52 which are rapidly emerging as a powerful prognostic marker in melanoma and a number of other cancer types53–55.”

    From Epigenetic state determines the in vivo efficacy of STING agonist therapy (2023) · cites this paper as [51]

    The Background identifies CXCL10 as one of the 12 chemokines in the signature, and the Results show that breast tumors with high signature scores had ectopic lymph node-like structures. The paper correlates the combined 12-chemokine score with these structures; it does not establish the correlation for CXCL10 expression individually. (LLM, conf=0.86)

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Authors
Prabhakaran, S., Rizk, V. T., Ma, Z., Cheng, C.-H., Berglund, A. E., Coppola, D., Khalil, F., Mulé, J. J., & Soliman, H. H.
Affiliations
  • Moffitt Cancer Center (US)
  • University of South Florida (US)
Corresponding author
Soliman, Hatem H.
ORCID
Venue
Breast Cancer Research
Publisher
Springer Science and Business Media LLC
Published
2017-06-19
Volume
19
Issue
1
Pages
71-71
ISSN
  • 1465-5411 (ISSN-L)
  • 1465-542X
DOI
10.1186/s13058-017-0864-z
PMC
PMC5477261
OpenAlex
W2656808027
Cited by
150
References
1
Citations by year
2026: 12 · 2025: 17 · 2024: 21 · 2023: 19 · 2022: 40 · 2021: 17 · 2020: 8 · 2019: 5 · 2018: 6 · 2017: 4 · 2012: 1
FWCI
2.11
Type
journal article
Language
en
Open access
Licence
Locations
  • Breast Cancer Research (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Cancer Institute (P30-CA076292)
  • V Foundation for Cancer Research
  • Jackie Lewis
  • Julie Wooley
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
  • Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Breast Lesions and Carcinomas
Keywords
invasive breast cancer, tumor microenvironment, prognostic factors, overall survival, recurrence-free survival, PAM50 molecular subtypes, basal-like breast cancer, HER2-positive breast cancer, gene expression profiling
MeSH terms
Adult, Aged, Aged, 80 and over, Breast Neoplasms, Female, Follow-Up Studies, Humans, Middle Aged, Neoplasm Invasiveness, Neoplasm Staging, Prognosis, Biomarkers, Tumor, Gene Expression, Chemokines, Gene Expression Profiling, Kaplan-Meier Estimate, Young Adult, Tumor Microenvironment, Neoplasm Grading

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