Breast cancer is pushed into first place in the United States and many other parts of world. Breast cancer alone is expected to account for 29% (226,870) of all new cancer cases among women . Although incidence rate of breast cancer remains relatively stable in recent 5 years, its death rate declines by 34% because of the development of diagnosis and targeting medication. TNBC accounts for about 15% of all breast cancers. Patients with TNBC are more likely to experience death and distant recurrence compared to those with other cancers, and the median time to death/distant recurrence is significantly shortened. TNBC is one of solid tumors which are sensitive to chemotherapy, but other modalities, such as endocrine and targeted therapy, are not applicable. So, it is crucial to find specific markers to detect micro metastases and provide useful information to guide early therapeutic methods of TNBC patients.
Although various biological markers had been proposed for the detection of breast cancer cells, they were often affected by tumor differentiation, lower specificity and detection rate. Cyclin D1 was an effective marker for the differential diagnosis of other papillary lesions. Because Cyclin D1expressed in both lesions, it could not be used to distinguish between papilloma and papillary carcinoma lesions . Petra Barros et al. found that the expression of β1 integrin had an impact in disease-specific survival (number of months from diagnosis to the time of death due to breast cancer) and could be a marker of poor prognosis in breast cancer . But, β1 integrin played a role in predicting the clinical course and prognosis of several types of cancers , especially abundant expressing in Non-small-cell lung carcinoma . By the same token, carcinoembryonic antigen (CEA) was not a specific marker of breast cancer because it was expressed at high levels in a variety of human tissues including lung, breast, and colorectal cancer. Although BRCA1 was associated with the genesis, progression, and prognosis of young breast cancer patients , they only accounted for about 5% of breast cancer occurrences . So, researchers are searching for more promising genes to improve the screen, diagnosis and prognosis predicting of breast cancer.
SBEM was tissue-specific protein and only expresses in mammary and salivary glands . SBEM could serve as a useful marker for breast nodal metastasis, and for detection of micro metastatic cells within lymph nodes. Also, it was used for the differential diagnosis of the primary origin of an unknown metastasis, especially in high grade and ER/PR-negative tumors . Hinde et al. confirmed that the predictive power of IHC criteria appeared to be similar to that of gene expression analysis. The IHC information could be used to improve therapeutic decisions, mainly for luminal B, Her2- over-expressing and basal-like subtypes . So, we examined SBEM levels in FFPE tissue sections by IHC test and then analyzed the correlation of SBEM expression with DFS and OS. Liu et al. reported that SBEM protein expression correlated with tumor size, TNM staging and lymph node metastasis . Ki67 is used to assess the prognosis of cancer patients . It would be indicated that SBEM were related to prognostic value with Ki67. Overall these risk factors, including age, grade, size, disease stage, lymph node status, and Ki67, were analyzed in our study. Our data showed that the detection rate of SBEM in FFPE tissue of TNBC was 58%, which was higher than previous report . SBEM expression levels positively correlated with DFS and OS in TNBC patients. The Cox’s proportional hazards regression model showed that SBEM was independent for grade, age, disease stage, lymph node status, and Ki67. When we adjusted SBEM to combine with each clinical risk factor, SBEM expression still remained significant. Multivariate analysis showed that patients with a high SBEM expression of 3+ represented a higher risk of recurrence and mortality than those with a low SBEM expression (HR = 3.370 with p = 0.008 for DFS and HR = 4.185 with p = 0.004 for OS). SBEM could be regarded as an independent prognostic factor in TNBC.
We believed that SBEM would show much more advantages than other protein–based biomarkers and would be used as prognostic indicator. Meanwhile, SBEM expression in PB (Peripheral blood) of breast cancer patients was markedly higher than that of healthy donors and other cancer patients . Determination of SBEM protein in tissue and mRNA expression in PB of TNBC patients maybe helpful for early diagnosis, choice of treatment, decision of the degree of malignancy and risk prediction of recurrence. However, it is necessary to determine the function of a certain gene by carrying out large sample studies or a large meta-analysis in different institutions and hospitals. In the past decade, the findings about the relationship between Catechol-O-methyltransferase Val158Met (COMT Val108/158Met) polymorphism and breast cancer risk were inconsistent. A large meta-analysis conducted by Xue Qin confirmed that COMT Val108/158Met polymorphism may not be associated with breast cancer risk . Similarly, the prognostic significance of SBEM needs further evidence in TNBC patients.
Due to different breast cancer subtype are associated with different gene expression patterns, it is significant to identify the particular gene to suit the proper biological characteristic of a certain type of primary tumor. SBEM over-expression maybe the special characteristic of tumor cells in TNBC. In conclusion, we have done some really nice research in which SBEM shows its prognostic value in TNBC. Our findings may eventually lead to wide application of SBEM as a tumor marker or a target gene for therapy and rapid development in the diagnostic and therapeutic products for TNBC patients in future.