Low LATS2 mRNA level can predict favorable response to epirubicin plus cyclophosphamide, but not to docetaxel, in breast cancers.
OBJECTIVE
Putative tumor suppressor genes LATS1 and LATS2 are implicated in the regulation of the cell cycle at the G2/M and G1/S phase, respectively. This study investigated possible correlations of intra-tumoral LATS1 and LATS2 mRNA levels with response to epirubicin plus cyclophosphamide (EC) or docetaxel (DOC) treatment.


METHODS
mRNA expression levels of LATS1 and LATS2 were determined by means of real-time PCR assay in 56 locally advanced breast cancers and 15 recurrent breast cancers treated with EC (n = 32) or DOC (n = 39).


RESULTS
Among the patients treated with EC, LATS2 mRNA levels of responders (0.72 +/- 0.11, mean +/- SE) were significantly (P < 0.05) lower than those of non-responders (1.62 +/- 0.44), and responders showed a tendency (P = 0.05) towards reduced LATS1 mRNA levels. Patients with low LATS2 mRNA levels (n = 16) showed a significantly (P < 0.05) higher response rate (75%) to EC treatment than those with high LATS2 mRNA levels (n = 16; response rate = 31%). Positive predictive value, negative predictive value, and diagnostic accuracy of LATS2 mRNA levels for prediction of response to EC were 75, 69, and 72%, respectively. On the other hand, neither LATS1 nor LATS2 mRNA levels were associated with response to DOC treatment.


CONCLUSIONS
These results suggest the possibility that intra-tumoral LATS2 mRNA levels may be clinically useful for the prediction of response to EC treatment by breast cancer patients. We speculate that disruption of the checkpoint function at the G1/S phase induced by down-regulation of LATS2 plays some part in the favorable response to EC.
Takahashi
Yuri
Y
Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, 2-2-E10 Yamada-oka, Suita, Osaka 565-0871, Japan.
Miyoshi
Yasuo
Y
Morimoto
Koji
K
Taguchi
Tetsuya
T
Tamaki
Yasuhiro
Y
Noguchi
Shinzaburo
S
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000188:drug therapy* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000032:analysis; D003520:Cyclophosphamide / Q000008:administration & dosage; D000077143:Docetaxel; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D064248:Geminin; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000032:analysis* / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000032:analysis* / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000032:analysis
D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; C577995:GMNN protein, human; D064248:Geminin; D012333:RNA, Messenger; D043823:Taxoids; D025521:Tumor Suppressor Proteins; D000077143:Docetaxel; D015251:Epirubicin; D003520:Cyclophosphamide; C513496:MIB1 ligase, human; D044767:Ubiquitin-Protein Ligases; C092745:LATS1 protein, human; C406449:LATS2 protein, human; D017346:Protein Serine-Threonine Kinases