Digestive Diseases and Sciences

, Volume 64, Issue 2, pp 439–446 | Cite as

Methylation Patterns of Lys9 and Lys27 on Histone H3 Correlate with Patient Outcome in Gastric Cancer

  • Yiping Li
  • Didi Guo
  • Rui Sun
  • Ping Chen
  • Qi Qian
  • Hong FanEmail author
Original Article



Histone methylation has been considered as one of the epigenetic mechanisms of carcinogenesis and progression. Researches on the correlation between histone lysine methylation and gastric cancer (GC) will help in finding novel epigenetic biomarkers for monitoring cancers.


The study detected the expression patterns of histone 3 lysine 9 dimethylation (H3K9me2), histone 3 lysine 9 trimethylation (H3K9me3), and histone 3 lysine 27 trimethylation (H3K27me3) in GC tissues and evaluated their clinical merit for GC patients.


One hundred thirty-three paraffin-embedded GC samples were examined by immunohistochemistry for the histone markers: H3K9me2, H3K9me3, and H3K27me3. The relationship and clinicopathological significance of the three lysine methylations on histone H3 with GC were assessed by Paired t test, Chi-square test, Kaplan–Meier analysis with log-rank test, and Cox proportional hazard analyses.


Strong positive immunostaining of H3K9me2, H3K9me3, and H3K27me3 was observed in cancerous tissues than in their counterpart non-cancer tissues. Higher expression patterns of H3K9me2, H3K9me3, and H3K27me3 significantly related to differentiation degree, lymph nodes metastases, and pathological TNM staging in GC. The GC patients with low scoring of the three markers implied long survival period and best prognosis. In contrast, the patients’ survival time was significantly shorter if their cancerous tissues presented high expression of the three markers.


H3K9me2, H3K9me3, and H3K27me3 expression patterns closely relate to clinicopathological features and may be the independent risk factors for the survival of GC patients. The combined pattern of the three markers rather than an individual marker is considered to more accurately evaluate the outcome of GC patients.


H3K9me2 H3K9me3 H3K27me3 Epigenetic marks Gastric cancer 



This work was supported by the grants from National Natural Science Foundation of China (81672414 and 81472548). This work was also supported by the Innovation Capability Development Project of Jiangsu Province (BM2015004).

Compliance with ethical standards

Conflict of interest

We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted.

Supplementary material

10620_2018_5341_MOESM1_ESM.tif (11.8 mb)
Fig. S1 The expression patterns for the stained histone markers by IHC assay. The expression was scored according to the staining intensity and staining area. The staining intensity was marked as the following, 0 for no staining, 1 for weak staining, 2 for moderate staining, 3 for intensive staining. Based on the percentage of positive cells in the observed epithelial tissues, the staining area was identified as 5 different levels. 0 for 0–5% positive cells, 1, 2, 3, 4 for 6–25%, 26–50%, 51–75%, and 76–100%, respectively. The final score is the product of the staining intensity and staining area. Low indicates for the tissues with the final score ≤ 8, high for the final score > 8. Scale bar = 200 μm (TIFF 12090 kb)
10620_2018_5341_MOESM2_ESM.docx (19 kb)
Supplementary material 2 (DOCX 18 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Medical Genetics and Developmental Biology, Medical School, The Key Laboratory of Developmental Genes and Human Diseases, Ministry of EducationSoutheast UniversityNanjingChina
  2. 2.Department of Pathology, Medical SchoolSoutheast UniversityNanjingChina
  3. 3.Institute of Life Science, The Key Laboratory of Developmental Genes and Human DiseasesSoutheast UniversityNanjingChina
  4. 4.Department of OncologyYancheng First People’s HospitalYanchengChina

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