Hsp70 (HSPA1) Lysine Methylation Status as a Potential Prognostic Factor in Metastatic High-Grade Serous Carcinoma

摘要: Cellular proteins are subject to frequent methylation on lysine residues, introduced by specific methyltransferases, and each residue can receive up three methyl groups. Histone methylations, which key determinants of chromatin state transcriptional status, have been particularly intense studies, but methylations non-histone protein substrates also abundant biologically significant. Numerous studies addressed in the realm cancer biology. A recent study used an antibody-based approach investigate Lys-561 stress-inducible Hsp70 HSPA1, focusing exclusively dimethylated concluding that it was elevated [Cho et al. (2012), Nat. Commun.,3, 1072]. In present study, we performed a more extensive analysis HSPA1 status samples, using mass spectrometry. We found four states Lys561 (un-, mono-, di- trimethylated) could be measured accurately reproducibly samples from carcinomas. investigated 70 effusions, representing 53 high-grade serous ovarian carcinomas 17 breast Notably, trimethylated form predominant samples. studied for association with clinicopathologic parameters, including chemotherapy response survival. The prevalent carcinoma effusions (p = 0.014), whereas 0.025), monomethylated 0.004) unmethylated 0.021) forms were overrepresented For carcinomas, 0.028) 0.007) significantly related presence higher residual disease volume, while associated poor overall 0.015) progression-free 0.012) conclusion, differs between metastatic carcinoma, shows potential as prognostic marker carcinoma.