The methylation profiles of PRDM promoters in non–small cell lung cancer

Abstract

BackgroundNon–small cell lung cancer (NSCLC) is one of the leading malignant tumors worldwide. Aberrant gene promoter methylation contributes to NSCLC, and PRDM is a tumor suppressor gene family that possesses histone methyltransferase activity. This study aimed to investigate whether aberrant methylation of PRDM promoter is involved in NSCLC.Materials and methodsPrimary tumor tissues, adjacent nontumorous tissues, and distant lung tissues were collected from 75 NSCLC patients including 52 lung squamous cell carcinoma (LSCC) patients and 23 lung adenocarcinoma patients. The expression of PRDMs was detected by polymerase chain reaction (PCR), Western blot, and immunohistochemical analysis. The methylation of PRDM promoters was detected by methylation-specific PCR. The correlation of methylation and expression of PRDMs with clinicopathological characteristics of patients were analyzed.ResultsmRNA expression of PRDM2, PRDM5, and PRDM16 was low or absent in tumor tissues compared to distant lung tissues. The methylation frequencies of PRDM2, PRDM5, and PRDM16 in tumor tissues were significantly higher than those in distal lung tissues. In LSCC patients, methylation of PRDM2 and PRDM16 was correlated with smoking status and methylation of PRDM5 was correlated with tumor differentiation.ConclusionThe expression of PRDM2, PRDM5, and PRDM16 is low or absent in NSCLC, and this is mainly due to gene promoter methylation. Smoking may be an important cause of PRDM2 and PRDM16 methylation in NSCLC.

Peer Review #1 of "The predictive value of PRDM2 in solid tumor: a systematic review and meta-analysis (v0.1)"

“…Out of these 58 studies, 52 were excluded due to the studies being unable to meet the inclusion criteria (ineligible), in vitro and/or in vivo, used unsuitable methods, written in non-English, or is a review. The remaining six studies (Akahira et al 2007;Dong et al 2012;Ge et al 2015;Geli et al 2005;Jiang et al 1999;Tan et al 2018) were included in the systematic review while only five studies (Akahira et al 2007;Dong et al 2012;Geli et al 2005;Jiang et al 1999;Tan et al 2018) were included in the meta-analysis. This is because Ge et al (2015) did not mention the number of samples and controls that expressed PRDM2 downregulation in renal cell carcinoma.…”

DNA Methylation Changes are Associated with the Programming of White Adipose Tissue Browning Features by Resveratrol and Nicotinamide Riboside Neonatal Supplementations in Mice

“…To be noted, the BS region studied encompasses Prdm16 promoter-proximal parts that are actively demethylated during brown adipogenesis, paralleling increased Prdm16 transcription [17]. Epigenetic regulation of Prdm16 through DNA methylation modification has also been demonstrated in peripheral blood of adolescents exposed to maternal diabetes in utero [43], the placenta of mothers with gestational diabetes [44], and in connection to cancer [45].…”

Multifaceted Role of PRDM Proteins in Human Cancer

“…Promoter methylation significantly correlated with tumor cell differentiation and lymph node metastasis, but not with tumor grade or other parameters like age, gender, and smoking [138]. Consistently, 5-aza-2'-deoxycitydine inhibited the proliferation of the SK-MES-1 lung cancer cell line and xenograft growth in nude mice, along with reduced PRDM5 promoter methylation and its consequent increased expression [138][139][140]. Overall, these data suggest that PRDM5 is a tumor suppressor in several human cancer types where it could represent a molecular marker for diagnosis and prognosis and a promising target for their therapy.…”

“…A possible role as a tumor suppressor gene has been proposed in lung cancer where PRDM16 is aberrantly methylated and its expression is low or absent [139,140]. Accordingly, the median overall survival of both non-small cell lung cancer and LUAD patients with high levels of PRDM16 was significantly longer than that of cases with low levels of this gene [254][255][256].…”