Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Dec 19:12:1048482.
doi: 10.3389/fonc.2022.1048482. eCollection 2022.

Low expression of H3K27me3 is associated with poor prognosis in conventional chordoma

Jie Wei  1 , Jianfeng Wu  1 , Zhiyong Yin  2 , Xia Li  1 , Yixiong Liu  1 , Yingmei Wang  1 , Zhe Wang  1 , Chao Xu  3   4 , Linni Fan  1
Affiliations

Low expression of H3K27me3 is associated with poor prognosis in conventional chordoma

Jie Wei et al. Front Oncol. .

Abstract

Purpose: Chordoma is a rare and locally invasive neoplasm, and the prognostic factors are limited. Deregulation of Histone 3 lysine 27 (H3K27) trimethylation (H3K27me3) is considered to be related with poor prognosis in some tumors. The purpose of this study was to detect the expression of H3K27me3 in chordomas and analyze the correlation with clinicopathological features and explore the roles as potential prognostic markers and therapeutic targets.

Material and method: Specimens of 162 chordoma patients (consisting of 156 conventional chordoma, 4 dedifferentiated chordoma and 2 poorly differentiated chordoma) were enrolled in a tissue microarray (TMA) in order to assess the immunohistochemical staining by H3K27me3 antibodies. Correlations between H3K27me3 expression and clinicopathological features were analyzed. Clinical data of the patients were correlated and survival analysis was performed. Kaplan-Meier survival curves and log-rank test were used to analyze the recurrence-free survival (RFS) and overall survival (OS). Multivariate Cox regression analyses were used to identify potential prognostic factors.

Results: The expression of H3K27me3 was lower in 37 chordoma patients (37/162, 22.8%), and higher in 125 patients (125/162, 77.2%). H3K27me3-low expression significantly correlated with spine location (P < 0.001), conventional histological subtype (P < 0.001), and recurrence (P < 0.001). Log-rank test showed that H3K27me3-low expression was associated with poor RFS (P =0.027) and OS (P =0.009) in conventional chordoma patients. Cox multivariate analysis revealed that low expression of H3K27me3 was an independent predictor of poor OS (P =0.007) and RFS (P =0.025) in conventional chordoma patients.

Conclusions: Our study indicates that low expression of H3K27me3 might be considered as a predictor for poor prognosis and recurrence, and it may provide a potential therapeutic target for conventional chordoma patients.

Keywords: H3K27me3; brachyury; chordoma; prognosis; recurrence.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Representative patterns of H3K27me3 staining in conventional chordoma tissue microarray. (A-D) HE stained tissue sections. (E, F) Low expression of H3K27me3 in conventional chordoma. (E) All tumor cells with no staining, (F) 10% tumor cells with moderate staining. (G, H) High expression of H3K27me3 in conventional chordoma. (G) 70% tumor cells with moderate staining, (H) all tumor cells with distinct and strong brown staining.
Figure 2
Figure 2
H3K27me3 expression in dedifferentiated chordoma and poorly differentiated chordoma tissues. (A) Dedifferentiated chordoma with typical features of conventional chordoma (right), and a transition to a high-grade pleomorphic sarcoma (left). (B) Poorly differentiated chordoma. (C) IHC staining of brachyury, noting that the dedifferentiated component did not express brachyury. (D) IHC staining of SMARCB1 (INI1), and the poorly differentiated chordoma showed loss of SMARCB1 (INI1). (E, F) IHC staining of H3K27me3, (E) Low expression of H3K27me3 in dedifferentiated component, (F) High expression of H3K27me3 in poorly differentiated chordoma.
Figure 3
Figure 3
Kaplan-Meier survival curve with log-rank test derived results of survival analysis. (A) Overall survival of 145 chordoma patients stratifed by the expression status of H3K27me3 in all patients, (B) Overall survival of 139 conventional chordoma patients stratifed by the expression level of H3K27me3. (C) Recurrence-free survival of 145 chordoma patients stratifed by the expression level of H3K27me3 in all patients, (D) Recurrence-free survival of 139 conventional chordoma patients stratifed by H3K27me3 status. Compared to the high expression group, patients with low H3K27me3 expression had significantly shorter overall survival and recurrence-free survival.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Casali PG, Bielack S, Abecassis N, Aro HT, Bauer S, Biagini R, et al. . Bone sarcomas: esmo-paedcan-euracan clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol (2018) 29(Suppl 4):v79–95. doi: 10.1093/annonc/mdy310 - DOI - PubMed
    1. Stiller CA, Trama A, Serraino D, Rossi S, Navarro C, Chirlaque MD, et al. . Descriptive epidemiology of sarcomas in europe: report from the rarecare project. Eur J Cancer (2013) 49(3):684–95. doi: 10.1016/j.ejca.2012.09.011 - DOI - PubMed
    1. Meng T, Jin J, Jiang C, Huang R, Yin H, Song D, et al. . Molecular targeted therapy in the treatment of chordoma: A systematic review. Front Oncol (2019) 9:30. doi: 10.3389/fonc.2019.00030 - DOI - PMC - PubMed
    1. Pan Y, Lu L, Chen J, Zhong Y, Dai Z. Analysis of prognostic factors for survival in patients with primary spinal chordoma using the seer registry from 1973 to 2014. J Orthop Surg Res (2018) 13(1):76. doi: 10.1186/s13018-018-0784-3 - DOI - PMC - PubMed
    1. Thanindratarn P, Dean DC, Nelson SD, Hornicek FJ, Duan Z. T-Lak cell-originated protein kinase (topk) is a novel prognostic and therapeutic target in chordoma. Cell Prolif (2020) 53(10):e12901. doi: 10.1111/cpr.12901 - DOI - PMC - PubMed

LinkOut - more resources