TMEM25, REPS2 and Meis 1: favourable prognostic and predictive biomarkers for breast cancer.

ABSTRACT

BACKGROUND/AIMS: A panel of prognostic and predictive biomarkers would contribute to personalized treatment of breast cancer patients. However, many such biomarkers have yet to be identified and evaluated. The aim of this study was to investigate the relevance of 3 such putative biomarkers. METHODS: TMEM25, REPS2 and Meis 1 expression was investigated by qRT-PCR, in triplicate, in 103 breast tumour biopsies procured in 1993-1994. Normal breast tissue specimens were also analysed for comparative purposes. Univariate and multivariate analyses were used to identify associations between expression of these transcripts as well as patients' clinicopathological and survival data. RESULTS: TMEM25, REPS2 and Meis 1 transcripts were detected in approximately 52, 78 and 40% of tumour specimens, respectively. Expression of each of the 3 genes was indicative of extended survival times from diagnosis [association between relapse-free survival (RFS) and TMEM25, p = 0.0002; REPS2, p = 0.0287; association between overall survival (OS) and TMEM25, p = 0.001; REPS2, p = 0.0131; Meis 1, p = 0.0255]. Presence of TMEM25 and Meis 1 was associated with oestrogen receptor-positive (TMEM25, p < 0.0005; Meis 1, p = 0.011), lower-grade (TMEM25, p = 0.002; Meis 1, p = 0.001) tumours. Multivariate analysis indicated TMEM25 expression to be an independent prognostic factor for extended RFS (p = 0.011) and OS (p = 0.001). Furthermore, for patients who received adjuvant chemotherapy, significantly longer survival times were achieved if their tumours expressed TMEM25 (OS, p = 0.031; RFS, p = 0.0181) and REPS2 (OS, p = 0.011). While expression of these mRNAs was generally absent from triple-negative breast tumours, statistical significance was not achieved. CONCLUSION: Our results suggest that TMEM25, REPS2 and Meis 1 mRNAs may be useful members of a panel of favourable prognostic and predictive markers for breast cancer and an understanding of their function may provide useful information about this disease.