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

Abstract

PurposeMore accurate prediction of patient outcome based on molecular subtype is required to identify patients who will benefit from specific treatments.MethodsWe 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.ResultsThe 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.ConclusionsOur 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.Electronic supplementary materialThe online version of this article (doi:10.1007/s10549-017-4234-4) contains supplementary material, which is available to authorized users.

Identification of gene modules associated with survival of diffuse large B-cell lymphoma treated with CHOP-based chemotherapy

“…The protein encoded by human CD2 gene was found on all peripheral blood T cells, and played an important role in immune recognition [37]. Study in HER2-positive breast cancer has found a long OS with the increased CD2 expression [38]. The product of GZMK is a member of a group of related serine proteases derives from the cytoplasmic granules of cytotoxic lymphocytes.…”

UBE2C Overexpression Aggravates Patient Outcome by Promoting Estrogen-Dependent/Independent Cell Proliferation in Early Hormone Receptor-Positive and HER2-Negative Breast Cancer

“…In a previous study, we performed subgroup analysis according to molecular breast cancer subtype using FFPE samples from 819 breast cancer patients. The results of univariate analysis showed that UBE2C mRNA expression as a continuous variable is statistically significantly associated with DFS, DMFS, and OS in only patients with HR+/HER2-breast cancer regardless of LN negativity or positivity (10). Of the previous cohort, 410 patients with HR+/HER2-breast cancer were included in this study; the detailed clinical characteristics of patients were shown in Table 1 chemotherapy, and histologic grade 2 was predominant in the patient group (48.5%, 199/410).…”

“…High UBE2C expression is associated with a high degree of malignancy, low differentiation, high metastatic tendency, and poor patient survival in a wide range of solid tumors including breast cancer (21)(22)(23)(24)(25). We previously reported that UBE2C is significantly associated with poor prognosis in patients with HR+/HER2-breast cancer (9,10). Consistent with our report, Filipits et al reported the use of UBE2C mRNA expression as a marker in the EndoPredict assay for predicting the risk of recurrence or distant metastasis in patients with HR+/HER2-breast cancer (8).…”

“…In a previous study, we identified 384 candidate prognostic genes associated with distant metastasis in patients with lymph node (LN) negative early breast cancer (9). Of these 384 genes, 16 candidate prognostic genes were selected, and the association between the expression of these genes determined by quantitative real-time reverse transcription-PCR (qRT-PCR) and clinical outcomes was evaluated in 997 FFPE tissue samples from 819 patients with breast cancer (9,10). Six genes were selected to develop a prognostic model for predicting the risk of distant recurrence or distant metastasis, and the performance of the model was compared with that of classical clinicopathological risk factors (10)(11)(12)(13).…”

Screening of a Novel Upregulated lncRNA, A2M-AS1, That Promotes Invasion and Migration and Signifies Poor Prognosis in Breast Cancer

“…CD2 and SELL participate in the leukocyte transendothelial migration pathway. CD2, which is regarded as an immune response molecule, has been documented to be involved in breast cancer recurrence and metastasis and to play a vital role as a prognostic factor for patients with breast cancer [31][32][33]. SELL is a cell surface adhesion molecule.…”