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


CONCLUSIONS
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.
National Institute for Cellular Biotechnology, Dublin City University, Dublin, Ireland.
P
P
Doolan
M
M
Clynes
S
S
Kennedy
J P
JP
Mehta
S
S
Germano
C
C
Ehrhardt
J
J
Crown
L
L
O'Driscoll
D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001706:Biopsy; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D002135:Calcium-Binding Proteins; D018572:Disease-Free Survival; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008207:Lymphatic Metastasis / Q000473:pathology; D008875:Middle Aged; D015999:Multivariate Analysis; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009362:Neoplasm Metastasis / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics*; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013629:Tamoxifen / Q000627:therapeutic use; D014158:Transcription, Genetic
D000970:Antineoplastic Agents; D002135:Calcium-Binding Proteins; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; C000616391:MEIS1 protein, human; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins; C489722:REPS2 protein, human; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D013629:Tamoxifen