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

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Abstract

Background

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.

Aims

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.

Methods

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.

Results

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.

Conclusions

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.

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Acknowledgments

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).

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Authors and Affiliations

  1. Department of Medical Genetics and Developmental Biology, Medical School, The Key Laboratory of Developmental Genes and Human Diseases, Ministry of Education, Southeast University, Nanjing, 210009, China

    Yiping Li, Rui Sun & Hong Fan

  2. Department of Pathology, Medical School, Southeast University, Nanjing, 210009, China

    Yiping Li

  3. Institute of Life Science, The Key Laboratory of Developmental Genes and Human Diseases, Southeast University, Nanjing, 210018, China

    Didi Guo

  4. Department of Oncology, Yancheng First People’s Hospital, Yancheng, 224005, China

    Ping Chen & Qi Qian

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  1. Yiping Li
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Correspondence to Hong Fan.

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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)

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Li, Y., Guo, D., Sun, R. et al. Methylation Patterns of Lys9 and Lys27 on Histone H3 Correlate with Patient Outcome in Gastric Cancer. Dig Dis Sci 64, 439–446 (2019). https://doi.org/10.1007/s10620-018-5341-8

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  • DOI: https://doi.org/10.1007/s10620-018-5341-8

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