Background : Inositol polyphosphate 5-phosphatase PIPP (INPP5J) has been identified as a suppressor of oncogenic PI3K/Akt signaling in breast cancer.INPP5J depletion increases transformation and accelerates oncogene-driven tumor growth in vivo, while paradoxically reducing cell migration, invasion, and metastasis. Therefore, we hypothesized that INPP5J gene expression in human breast cancer tissues would be prognostic in early breast cancer patients over long-term follow-up.
Methods: A total of 478 breast cancer tissue samples collected between 2003 and 2008 was available for analysis. We measured INNPP5J mRNA using a TaqMan gene expression assay. PIK3CA mutation status was evaluated using a TaqMan mutation detection assay. We then investigated the correlations of clinicopathological factors and prognosis with levels of INPP5J mRNA and the PIK3CA mutation status.
Results: INPP5J mRNA was expressed at a low level in 30.1% (144/478) and at a medium to high level in the remaining breast cancer samples. Low INPP5J mRNA correlated with larger tumor (p=0.015), high grade (p<0.0001) and, ER-negativity (p<0.0001). PIK3CA mutations were detected in 46% (63/138) of patients analyzed. We found that disease-free survival (DFS) was significantly worse in patients with low levels of INPP5J (p=0.008). Although DFS and INPP5J levels tended to be associated in estrogen receptor (ER)-positive patients (p=0.052), DFS was significantly worse in patients with wild-type PIK3CA and low INPP5J mRNA expression (p=0.008).
Conclusion: We shows that the level of INPP5J mRNA expression is prognostics in breast cancer patients and that its prognostic impact is affected by PIK3CA mutation status.
Citation Format: Kondo N, Kim T-S, Wanifuchi Y, Hato Y, Hisada T, Nishimoto M, Nishikawa S, Toyama T. The prognostic impact of inositol polyphosphate 5-phosphatase PIPP (INPP5J) expression in breast cancer tissue [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-07-34.