Ann Surg Treat Res.  2018 Jan;94(1):19-25. 10.4174/astr.2018.94.1.19.

Epigenetic inactivation of RUNX3 in colorectal cancer

• Shin EJ
• Kim HJ
• Son MW
• Ahn TS
• Lee HY
• Lim DR
• Bae SB
• Jeon S
• Kim H
• Jeong D
• Lee MS
• Kim DS
• Noh JS
• Baek MJ

• KMID: 2405335
• DOI: http://doi.org/10.4174/astr.2018.94.1.19

Abstract

PURPOSE
Emerging evidence indicates that runt-related transcription factor 3 (RUNX3) is an important tumor suppressor gene in several cancer types, including colorectal cancer (CRC). However, the clinical significance of RUNX3 inactivation in CRC remains unclear. The aim of this study was to examine the correlation between clinicopathologic factors and RUNX3 hypermethylation/expression in CRC.
METHODS
Sixty-two CRC patients who were treated at the Soonchunhyang University College of Medicine were recruited in this study. The hypermethylation of CpG islands in the RUNX3 promoter and the expression of RUNX3 mRNA were identified by methylation-specific polymerase chain reaction (PCR) and reverse transcriptase-PCR, respectively. The expression of RUNX3 was determined by immunohistochemical staining.
RESULTS
Of the 62 CRC tissue samples, 20 (32.3%) presented hypermethylated RUNX3 promoters. Aberrant RUNX3 hypermethylation was found to be associated with vascular (P = 0.006) and lymphatic (P = 0.002) invasion. Hypermethylation of RUNX3 was associated with poor survival outcomes (P = 0.038). However, expression of RUNX3 was not a prognostic factor (P = 0.363).
CONCLUSION
Hypermethylation of RUNX3 may be a predictor of a poor prognosis in CRC.

Keyword

Colorectal neoplasms; Prognosis; RUNX3 protein; Methylation; Immunohistochemistry

MeSH Terms

Colorectal Neoplasms*
Core Binding Factor Alpha 3 Subunit
CpG Islands
Epigenomics*
Genes, Tumor Suppressor
Humans
Immunohistochemistry
Methylation
Polymerase Chain Reaction
Prognosis
RNA, Messenger
Transcription Factor 3
Core Binding Factor Alpha 3 Subunit
RNA, Messenger
Transcription Factor 3

Figure

• 

  Fig. 1 Immunohistochemical staining for RUNX3 (×400). (A) RUNX3 was not expressed in normal colonic mucosa tissue. RUNX3 was strongly (3+) (B), moderately (2+) (C), and weakly (1+) (D) expressed in colorectal cancer tissues. RUNX3, runt-related transcription factor 3.

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  Fig. 2 Methylation-specific polymerase chain reaction (PCR) analysis of RUNX3 promotor in colorectal cancer tissues. Methylated allele was detected in sample number 32, 37, 40, 56, 57, 58. RUNX3, runt-related transcription factor 3; M, methylated PCR product; U, unmethylated PCR product; SM, size marker.

• 

  Fig. 3 Reverse transcription-polymerase chain reaction analysis of RUNX3 gene expression in colorectal cancer tissues. RUNX3 expression was abolished in sample number 42, 43, 44, 46, 48, 51. SM, size marker; RUNX3, runt-related transcription factor 3; GAPDH, Glyceraldehyde 3-phosphate dehydrogenase.

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  Fig. 4 Kaplan-Meier survival analysis for colorectal cancer patients according to RUNX3 hypermethylation. RUNX3, runt-related transcription factor 3.

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  Fig. 5 Kaplan-Meier survival analysis for colorectal cancer patients according to expression of RUNX3. RUNX3, runt-related transcription factor 3.

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