Introduction/Background The phosphoinositide 3-kinase (PI3K) signaling cascade is one of the most frequently deregulated cascades in human cancers. The possibility of its inhibiting makes the PI3K pathway an attractive target for personalized therapy. We aimed to determine mRNA expression of PIK3R1, a gene encoding the p85α regulatory subunit of PI3K.
Methodology PIK3R1 mRNA expression analysis was carried out for 144 ovarian cancers and 5 specimens of noncancerous fallopian tube as a control group. Expression was evaluated using the quantitative PCR (qPCR) method and TaqMan Gene Expression Assays. Statistical analyses were done with the Mann-Whitney U test, the Cox’s and logistic regression models.
Results PIK3R1 mRNA expression was significantly decreased in ovarian cancers compared with control tissues (P=0.0028). The difference in mean expressions between cancers and normal tissues was 70% (0.1167±0.34 and 0.3981±0.13 in ovarian cancers and a control group, respectively). Reduced expression may be a consequence of allele loss of the PIK3R1 gene, because there is an association between mRNA level and copy number alteration of the gene (P=0.0001). Lower level of PIK3R1 mRNA was observed in non-serous (P=0.0437), poorly or mostly undifferentiated ovarian cancers (P=0.0114) diagnosed in patients under 54 years of age (P=0.077). Reduced expression of PIK3R1 was associated with the presence of TP53 mutation (P=0.0106) but not with PTEN loss or PIK3CA amplification. Patients overall survival, disease-free survival, complete remission and platinum sensitivity were not associated with PIK3R1 mRNA expression level.
Conclusion Ovarian cancers have decreased PIK3R1 expression at mRNA level and it may be a consequence of the PIK3R1 gene copy loss.
Grant Support This study was supported by the grant no. 2016/23/B/NZ5/00572 of the National Science Centre, Poland.
Disclosure Nothing to disclose.
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