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. 2018 May 22:11:2991-3002.
doi: 10.2147/OTT.S156775. eCollection 2018.

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

Shuang-Xiang Tan  1   2 , Rui-Cheng Hu  1   2 , Qian Xia  2 , Yong-Li Tan  1 , Jing-Jing Liu  1 , Gui-Xiang Gan  1 , Li-le Wang  1
Affiliations

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

Shuang-Xiang Tan et al. Onco Targets Ther. .

Abstract

Background: Non-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 methods: Primary 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.

Results: mRNA 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.

Conclusion: The 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.

Keywords: PR domain zinc finger protein; epigenetics; gene expression; lung tumor; methylation.

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Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Representative RT-PCR results to detect the expression of PRDM mRNAs in tumor tissues, adjacent tissues, and distant lung tissues of lung squamous cell carcinoma patients. Note: Lane 1–10: samples from no. 1–10 patients. Abbreviations: RT-PCR, reverse transcription polymerase chain reaction; PRDM, PR domain zinc finger protein; Mkr, marker.
Figure 2
Figure 2
Representative RT-PCR results to detect the expression of PRDM mRNAs in tumor tissues, adjacent tissues, and distant lung tissues of lung adenocarcinoma patients. Note: Lane 1–7: samples from no. 1–7 patients. Abbreviations: RT-PCR, reverse transcription polymerase chain reaction; PRDM, PR domain zinc finger protein; Mkr, marker.
Figure 3
Figure 3
Representative MSP results to detect the methylation of PRDM2, PRDM5, and PRDM16 promoters in tumor tissues, adjacent tissues, and distant lung tissues of lung squamous cell carcinoma patients. Note: Lane 1–10: samples from no. 1–10 patients. Abbreviation: MSP, methylation-specific polymerase chain reaction; Mkr, marker; M, methylated; UM, unmethylated.
Figure 4
Figure 4
Representative MSP results to detect the methylation of PRDM2, PRDM5, and PRDM16 promoters in tumor tissues, adjacent tissues, and distant lung tissues of lung adenocarcinoma patients. Note: Lane 1–7: samples from no. 1–7 patients. Abbreviation: MSP, methylation-specific polymerase chain reaction; Mkr, marker; M, methylated; UM, unmethylated.
Figure 5
Figure 5
Western blot analysis of PRDM expression in clinical samples. Notes: (A) Representative blots showing the expression of PRDM proteins in tumor tissues, adjacent tissues, and distant lung tissues of lung squamous cell carcinoma patients. M: marker; lane 1–10: samples from no. 1–10 patients. (B) Representative blots showing the expression of PRDM proteins in tumor tissues, adjacent tissues, and distant lung tissues of lung adenocarcinoma patients. M: marker; lane 1–7: samples from no. 1–7 patients. (C) Densitometry analysis of relative levels of PRDM proteins as shown in A and B. ▲Comparison with tumor tissue, <0.05; ★Compared with adjacent tissues, P<0.05. Abbreviation: PRDM, PR domain zinc finger protein.
Figure 6
Figure 6
Representative immunohistochemical staining of PRDM2, PRDM5, and PRDM16 in clinical samples. Note: Magnification: 200×. Abbreviation: Sq-cell, squamous cell.
See this image and copyright information in PMC

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