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PIK3CA expression in diffuse large B cell lymphoma tissue and the effect of its knockdown in vitro
Wenli Cui1,2,3,4, Shutao Zheng5,6, Zebing Liu1,2,3
1Department of Pathology, Shanghai Cancer Center, Fudan University.
Abstract:
PIK3CA has been extensively investigated from its molecular mechanism perspective and epidemiological association with its mutations in different types of cancers. However, little has been reported regarding the clinicopathological significance of PIK3CA expression in diffuse large B cell lymphoma (DLBCL). In the present study, we investigated the clinicopathological significance of PIK3CA in DLBCL by performing immunohistochemical evaluation of PIK3CA in tissue microarrays consisting of 199 cases of DLBCL. Kaplan-Meier survival analysis was performed to analyze the association between PIK3CA expression and overall prognosis. To further investigate the role of PIK3CA mediated in the proliferation, cell cycle and apoptosis of DLBCL cells, Cell Counting Kit-8 (CCK-8) and flow cytometry assays were carried out in DLBCL cell lines after successful, stable knockdown of PIK3CA using lentiviral short hairpin RNA inference. Our results indicated that although PIK3CA was shown to be extensively expressed in DLBCL, no significant association was observed between PIK3CA expression and clinical outcome or between PIK3CA expression and other clinicopathological parameters, except between performance state (PS) and phosphorylated AKT (p-AKT) expression. In vitro studies revealed that in DLBCL cell lines OCI-LY8 and OCI-LY1, knockdown of PIK3CA could significantly reduce proliferation and promote apoptosis in a G1-phase arrested manner. Additionally, p27 was shown to be markedly upregulated, whereas p-AKT and cyclin D1 were found to be pronouncedly downregulated after stable knockdown of PIK3CA. Together, our results support the oncogenic property of PIK3CA in DLBCL.
Insights
This study investigated Phosphoinositide 3-kinase catalytic subunit alpha (PIK3CA) expression in diffuse large B cell lymphoma (DLBCL). PIK3CA knockdown inhibited DLBCL cell proliferation and promoted apoptosis, supporting its oncogenic role.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Phosphoinositide 3-kinase catalytic subunit alpha (PIK3CA) is crucial in various cancers.
- Limited data exists on PIK3CA's clinicopathological significance in diffuse large B cell lymphoma (DLBCL).
Purpose of the Study:
- To evaluate the clinicopathological significance of PIK3CA expression in DLBCL.
- To investigate PIK3CA's role in DLBCL cell proliferation, cell cycle, and apoptosis.
Main Methods:
- Immunohistochemical evaluation of PIK3CA in 199 DLBCL tissue microarrays.
- Kaplan-Meier survival analysis for prognosis.
- In vitro studies using DLBCL cell lines with PIK3CA knockdown (lentiviral shRNA), CCK-8, and flow cytometry.
Main Results:
- PIK3CA was extensively expressed in DLBCL but showed no significant association with clinical outcome or most clinicopathological parameters.
- PIK3CA knockdown in DLBCL cell lines (OCI-LY8, OCI-LY1) significantly reduced proliferation and induced apoptosis via G1-phase arrest.
- Knockdown led to upregulation of p27 and downregulation of phosphorylated AKT (p-AKT) and cyclin D1.
Conclusions:
- PIK3CA expression lacks direct prognostic value in DLBCL.
- PIK3CA plays an oncogenic role in DLBCL by promoting proliferation and inhibiting apoptosis.
- Targeting PIK3CA may offer therapeutic potential for DLBCL.
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