High expression of gabarapl1 is associated with a better outcome for patients with lymph node-positive breast cancer.
BACKGROUND
This study evaluates the relation of the early oestrogen-regulated gene gabarapl1 to cellular growth and its prognostic significance in breast adenocarcinoma.


METHODS
First, the relation between GABARAPL1 expression and MCF-7 growth rate was analysed. Thereafter, by performing macroarray and reverse transcriptase quantitative-polymerase chain reaction (RT-qPCR) experiments, gabarapl1 expression was quantified in several histological breast tumour types and in a retrospective cohort of 265 breast cancers.


RESULTS
GABARAPL1 overexpression inhibited MCF-7 growth rate and gabarapl1 expression was downregulated in breast tumours. Gabarapl1 mRNA levels were found to be significantly lower in tumours presenting a high histological grade, with a lymph node-positive (pN+) and oestrogen and/or progesterone receptor-negative status. In univariate analysis, high gabarapl1 levels were associated with a lower risk of metastasis in all patients (hazard ratio (HR) 4.96), as well as in pN+ patients (HR 14.96). In multivariate analysis, gabarapl1 expression remained significant in all patients (HR 3.63), as well as in pN+ patients (HR 5.65). In univariate or multivariate analysis, gabarapl1 expression did not disclose any difference in metastasis risk in lymph node-negative patients.


CONCLUSIONS
Our data show for the first time that the level of gabarapl1 mRNA expression in breast tumours is a good indicator of the risk of recurrence, specifically in pN+ patients.
Berthier
A
A
Université de Franche-Comté, UFR Sciences et Techniques, Besançon, France.
Seguin
S
S
Sasco
A J
AJ
Bobin
J Y
JY
De Laroche
G
G
Datchary
J
J
Saez
S
S
Rodriguez-Lafrasse
C
C
Tolle
F
F
Fraichard
A
A
Boyer-Guittaut
M
M
Jouvenot
M
M
Delage-Mourroux
R
R
Descotes
F
F
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D011379:Prognosis; D012008:Recurrence; D012189:Retrospective Studies; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; C430503:GABARAPL1 protein, human; D008869:Microtubule-Associated Proteins