Stanniocalcin 2 expression is associated with a favourable outcome in male breast cancer

Abstract

Breast cancer can occur in either gender; however, it is rare in men, accounting for <1% of diagnosed cases. In a previous transcriptomic screen of male breast cancer (MBC) and female breast cancer (FBC) occurrences, we observed that Stanniocalcin 2 (STC2) was overexpressed in the former. The aim of this study was to confirm the expression of STC2 in MBC and to investigate whether this had an impact on patient prognosis. Following an earlier transcriptomic screen, STC2 gene expression was confirmed by RT‐qPCR in matched MBC and FBC samples as well as in tumour‐associated fibroblasts derived from each gender. Subsequently, STC2 protein expression was examined immunohistochemically in tissue microarrays containing 477 MBC cases. Cumulative survival probabilities were calculated using the Kaplan–Meier method and multivariate survival analysis was performed using the Cox hazard model. Gender‐specific STC2 gene expression showed a 5.6‐fold upregulation of STC2 transcripts in MBC, also supported by data deposited in Oncomine™. STC2 protein expression was a positive prognostic factor for disease‐free survival (DFS; Log‐rank; total p = 0.035, HR = 0.49; tumour cells p = 0.017, HR = 0.44; stroma p = 0.030, HR = 0.48) but had no significant impact on overall survival (Log‐rank; total p = 0.23, HR = 0.71; tumour cells p = 0.069, HR = 0.59; stroma p = 0.650, HR = 0.87). Importantly, multivariate analysis adjusted for patient age at diagnosis, node staging, tumour size, ER, and PR status revealed that total STC2 expression as well as expression in tumour cells was an independent prognostic factor for DFS (Cox regression; p = 0.018, HR = 0.983; p = 0.015, HR = 0.984, respectively). In conclusion, STC2 expression is abundant in MBC where it is an independent prognostic factor for DFS.

New Insights Into Physiological and Pathophysiological Functions of Stanniocalcin 2

“…STC2 also suppressed breast cancer cell migration and invasion by PKC/claudin1 mediated signaling (41,43). STC2 expression was also associated with positive outcome in male breast cancer (79). Taken together, except in breast cancer, STC2 expression is a potential prognostic marker for variety of cancers which promotes tumor cell growth, invasion and migration.…”

Apoptotic caspases inhibit abscopal responses to radiation and identify a new prognostic biomarker for breast cancer patients

“…49 Differential gene expression analysis of patient subgroups with good versus bad survival (based on 4 independent signatures of apoptotic proficiency) identified 11 genes similarly enriched in either of these groups, 8 of which had previously been attributed an impact on breast cancer progression or patient survival ( Figures 5 and 6). 34,[37][38][39][40][41][42][43] The expression levels of these genes also conveyed prognostic value in patients from the METABRIC dataset ( Figure 6 and Tables 1and 2), with the potential exception of CYP4X1. Of the remaining three genes, LTB failed to impact cancer-specific overall survival in the METABRIC cohort (Tables 1 and 2), while both CLIC6 and SLC7A2 were strongly associated with improved disease outcome ( Figure 6 and Tables 1 and 2), although only SLC7A2 as an independent prognostic biomarker ( Table 2).…”

“…Strikingly, 7 of these 11 genes have previously been attributed an impact on breast cancer progression and patient survival that is in line with our findings. These genes are AGR3, 34 ANKRD30A, 35 BMPR1B, 36,37 STC2 38,39 and SUSD3, 40 which are all indicators of early disease or good prognosis, as well as CXCL9, 41,42 and CALML5, 43 both of which have previously been linked to disease progression or poor prognosis. Conversely, CYP4X1 (which is our hands was enriched in patients with good survival) has previously been positively correlated with tumor grade.…”

Effect of STC2 gene silencing on colorectal cancer cells

“…It is highly important to identify new colorectal cancer (CRC) treatment targets. It has been reported that stanniocalcin 2 (STC2) is involved in the progression of various types of cancer, such as gastric and breast cancer (22,23). The differential expression levels of STC2 have certain guiding significance for the prediction, metastasis and prognosis of various malignant tumors (24).…”