MMP11 and CD2 as novel prognostic factors in hormone receptor-negative, HER2-positive breast cancer

Jinil Han ¹, Yoon-La Choi ², Haein Kim ³, Jun Young Choi ³, Se Kyung Lee ⁴, Jeong Eon Lee ⁵, Joon-Seok Choi ⁶, Sarah Park ⁷, Jong-Sun Choi ⁷, Young Deug Kim ⁸, Seok Jin Nam ⁴, Byung-Ho Nam ⁹, Mi Jeong Kwon ¹⁰, Young Kee Shin ¹¹

Affiliations

¹ Gencurix, Inc., Seoul, 08394, Korea.
² Laboratory of Cancer Genomics and Molecular Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 06356, Korea.
³ Laboratory of Molecular Pathology and Cancer Genomics, Department of Pharmacy, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, Korea.
⁴ Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 06356, Korea.
⁵ Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, 06356, Korea.
⁶ College of Pharmacy, Catholic University of Daegu, Gyeongbuk, 38430, Korea.
⁷ The Center for Anti-cancer Companion Diagnostics, Bio-MAX/N-Bio, Seoul National University, Seoul, 08826, Korea.
⁸ R&D center, ABION Inc., Seoul, 08394, Korea.
⁹ Department of Cancer Control and Policy, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Gyeonggi-do, 10408, Korea.
¹⁰ College of Pharmacy, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu, 41566, Korea. mjkwon94@knu.ac.kr.
¹¹ Laboratory of Molecular Pathology and Cancer Genomics, Department of Pharmacy, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, Korea. ykeeshin@snu.ac.kr.

PMID: 28409241
41 References
11 citations

Abstract

Purpose: More accurate prediction of patient outcome based on molecular subtype is required to identify patients who will benefit from specific treatments.

Methods: We selected novel 16 candidate prognostic genes, including 10 proliferation-related genes (p-genes) and 6 immune response-related genes (i-genes), from the gene list identified in our previous study. We then analyzed the association between their expression, measured by quantitative real-time reverse transcription-PCR in formalin-fixed, paraffin-embedded tissues, and clinical outcome in 819 breast cancer patients according to molecular subtype.

Results: The prognostic significance of clinical and gene variables varied according to the molecular subtype. Univariate analysis showed that positive lymph node status was significantly correlated with the increased risk of distant metastasis in all subtypes except the hormone receptor-negative, HER2-positive (HR-/HER2+) subtype. Most p-genes were significantly associated with poor prognosis in patients with the HR+/HER2- subtype, whereas i-genes correlated with a favorable outcome in patients with HR-/HER2+ breast cancer. In HR-/HER2+ breast cancer, four genes (three i-genes BTN3A2, CD2, and TRBC1 and the p-gene MMP11) were significantly associated with distant metastasis-free survival (DMFS). A new prognostic model for HR-/HER2+ breast cancer based on the expression of MMP11 and CD2 was developed and the DMFS for patients in the high-risk group according to our model was significantly lower than that for those in the low-risk group. Multivariate analyses revealed that our risk score is an independent prognostic factor for DMFS. Moreover, C-index showed that our risk score has a superior prognostic performance to traditional clinicopathological factors.

Conclusions: Our new prognostic model for HR-/HER2+ breast cancer provides more accurate information on the risk of distant metastasis than traditional clinical prognostic factors and may be used to identify patients with a good prognosis in this aggressive subtype of breast cancer.

Keywords: Breast cancer; HER2-positive (HR−/HER2+) breast cancer; Hormone receptor-negative; Immune response-related genes (i-genes); Prognostic model; Proliferation-related genes (p-genes); Risk of distant metastasis.

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