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 Jan 6;23(2):626.
doi: 10.3390/ijms23020626.

Telomere and Telomerase-Associated Proteins in Endometrial Carcinogenesis and Cancer-Associated Survival

Lucy Button  1 , Bryony Rogers  1 , Emily Thomas  1 , Alice Bradfield  2 , Rafah Alnafakh  1 , Josephine Drury  1 , Dharani K Hapangama  1   2
Affiliations

Telomere and Telomerase-Associated Proteins in Endometrial Carcinogenesis and Cancer-Associated Survival

Lucy Button et al. Int J Mol Sci. .

Abstract

Risk of relapse of endometrial cancer (EC) after surgical treatment is 13% and recurrent disease carries a poor prognosis. Research into prognostic indicators is essential to improve EC management and outcome. "Immortality" of most cancer cells is dependent on telomerase, but the role of associated proteins in the endometrium is poorly understood. The Cancer Genome Atlas data highlighted telomere/telomerase associated genes (TTAGs) with prognostic relevance in the endometrium, and a recent in silico study identified a group of TTAGs and proteins as key regulators within a network of dysregulated genes in EC. We characterise relevant telomere/telomerase associated proteins (TTAPs) NOP10, NHP2, NOP56, TERF1, TERF2 and TERF2IP in the endometrium using quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC). qPCR data demonstrated altered expression of multiple TTAPs; specifically, increased NOP10 (p = 0.03) and reduced NHP2 (p = 0.01), TERF2 (p = 0.01) and TERF2IP (p < 0.003) in EC relative to post-menopausal endometrium. Notably, we report reduced NHP2 in EC compared to post-menopausal endometrium in qPCR and IHC (p = 0.0001) data; with survival analysis indicating high immunoscore is favourable in EC (p = 0.0006). Our findings indicate a potential prognostic role for TTAPs in EC, particularly NHP2. Further evaluation of the prognostic and functional role of the examined TTAPs is warranted to develop novel treatment strategies.

Keywords: endometrial cancer; endometrium; immunohistochemistry; protein; qPCR; telomerase; telomere.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
The Structure of the human telomere and telomerase. Telomere is composed of tandem repeats of nucleotide sequence TTAGGG with a single stranded G-rich 3′ overhang. The six-protein complex shelterin or telosome protects telomere ends. TERF1, TERF2 and POT1 directly bind to the telomere interconnected by TERF2IP, TIN2 and TPP1. Telomerase is comprised of three main components hTERT, hTERC and DKC1. hTERC harbours an H/ACA motif which is associated with DKC1 and small nucleolar RNPs NOP10, NHP2 and GAR1.
Figure 2
Figure 2
qPCR data for selected telomere and telomerase associated transcripts NOP10, NHP2, NOP56, TERF1, TERF2 and TERF2IP. Individual points shown are the mean of technical triplicates, with the median indicated by the line. Post-menopausal, n = 6; Cancer, n = 21 for all genes examined.
Figure 3
Figure 3
Scatterplots to show Quickscores for NOP10, NHP2, NOP56, TERF1, TERF2 and TERF2IP. Line indicates median. NOP10 pre-menopausal n = 12, post-menopausal n = 11 (pre-menopausal vs. postmenopausal p = 0.059), cancer n = 39; NHP2 pre-menopausal n = 12, post-menopausal n = 11, cancer n = 41; NOP56 pre-menopausal n = 7, post-menopausal n = 12, cancer n = 43; TERF1 pre-menopausal n = 6, post-menopausal n = 10, cancer n = 30; TERF2 pre-menopausal n = 12, post-menopausal n = 16, cancer n = 51; TERF2IP pre-menopausal n = 12, post-menopausal n = 17, cancer n = 57.
Figure 4
Figure 4
Representative photomicrographs of NOP10, NHP2, NOP56, TERF1, TERF2 and TERF2IP immunohistochemical staining in human endometrial samples from pre-menopausal, post-menopausal and cancer patients. Magnification 40×, scale bar is 60 microns. Positive staining appears brown.
Figure 5
Figure 5
Survival curves obtained from IHC Quickscores of experimental data. Low quickscore data shown in grey, high quickscore data in black. (a) Overall survival (OS). Low NOP10 n = 15, high NOP10 n = 26, p = 0.56; low NHP2 n = 27 median survival 14 months, high NHP2 n = 12, median survival undefined, p = 0.0006; low NOP56 n = 27, median survival 30 months, high NOP56 n = 16 median survival 16 months, p = 0.02; low TERF1 n = 19, high TERF1 n = 11, p = 0.78; low TERF2 n = 41, high TERF2. n = 11, p = 0.97; low TERF2IP n = 25, high TERF2IP n = 33, p = 0.69. (b) Disease-free survival (DFS). Low NOP10 n = 15, high NOP10 n = 26, p = 0.8; low NHP2 n = 27 median DFS 11.5 months, high NHP2 n = 12, median DFS undefined, p < 0.005; low NOP56 n = 27, median DFS undefined, high NOP56 n = 16 median DFS 10 months, p < 0.05; low TERF1 n = 19, high TERF1 n = 11, p = 0.69; low TERF2 n = 41, high TERF2. n = 11, p = 0.96; low TERF2IP n = 25, high TERF2IP n = 33, p = 0.70.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Amant F., Moerman P., Neven P., Timmerman D., Van Limbergen E., Vergote I. Endometrial cancer. Lancet. 2005;366:491–505. doi: 10.1016/S0140-6736(05)67063-8. - DOI - PubMed
    1. Cancer Research UK Uterine Cancer Statistics. [(accessed on 10 October 2021)]. Available online: https://www.cancerresearchuk.org/health-professional/cancer-statistics/s....
    1. Fung-Kee-Fung M., Dodge J., Elit L., Lukka H., Chambers A., Oliver T. Follow-up after primary therapy for endometrial cancer: A systematic review. Gynecol. Oncol. 2006;101:520–529. doi: 10.1016/j.ygyno.2006.02.011. - DOI - PubMed
    1. Adishesh M., Hapangama D.K. Enriching Personalized Endometrial Cancer Research with the Harmonization of Biobanking Standards. Cancers. 2019;11:1734. doi: 10.3390/cancers11111734. - DOI - PMC - PubMed
    1. Meyne J., Ratliff R.L., Moyzis R.K. Conservation of the human telomere sequence (TTAGGG)n among vertebrates. Proc. Natl. Acad. Sci. USA. 1989;86:7049–7053. doi: 10.1073/pnas.86.18.7049. - DOI - PMC - PubMed