Abstract: Objective To investigate the expression of peptidylarginine deiminase 2 and 4 (PAD2 and PAD4) in malignant mesothelioma (MM), their correlation with citrullinated proteins and clinical significance. Methods The pathological samples of 45 cases of MM in Zhejiang province from 2014 to 2021 were collected retrospectively for constructing paraffin-embedded tissue microarray. The expressions of PAD2 and PAD4 in tumor and paired adjacent tissues were detected by immunohistochemistry and the clinical significance was analyzed by utilizing bioinformatics database. Results The expressions of PAD2 and PAD4 in MM tissues were significantly higher than those in adjacent tissues (P<0.05). The protein expression of PAD2 and PAD4 was positively correlated with epithelial mesothelioma, peritoneal mesothelioma and pleural mesothelioma (P<0.05). There was a positive correlation between PAD2 and PAD4 mRNA transcription level (P<0.05). The expressions of PAD2 and PAD4 were positively correlated with citrullinated proteins, respectively (P<0.05). The overall survival(OS) of PAD2 and PAD4 high expression group was shorter than that of low expression group, the progression free interval(PFI) of PAD4 high expression group was longer than that of low expression group (P<0.05). Conclusions PAD2 and PAD4 are potentially involved in the progression and prognosis of MM as biomarkers or therapeutic targets.

Key words: malignant mesothelioma, peptidylarginine deiminase 2, peptidylarginine deiminase 4, citrullination