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

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.

TRB CDR3 chemical complementarity with HBV epitopes correlates with increased hepatocellular carcinoma, disease‐free survival

“…NHP2, otherwise known as H/ACA ribonucleoprotein complex subunit, is an oncogene, like BRF2, and belongs to the H/ACA small nucleolar ribonucleoprotein (snoRNP) gene family and plays a crucial role in ribosome formation 36 and formation of the telomerase complex 37 . This latter function accounts for the gene's oncogenicity with increased expression having been observed in numerous cancers, such as endometrial cancer, 38 colorectal cancer, 39,40 and squamous cell lung cancer 41 . Most pertinent to this report, higher expression of NHP2, as well as other H/ACA snoRNP family genes, has also been correlated with poorer prognoses for HCC patients 42 .…”

Ribosome biogenesis‐based predictive biomarkers in endocrine therapy (Anastrozole) combined with mTOR inhibitor (Vistusertib) in endometrial cancer: translational study from the VICTORIA trial in collaboration with the GINECO group

“…mRNA levels of NHP2 and NOP10 indeed specifically distinguished non‐responders from responders to the Vistusertib + Anastrozole combination. Interestingly, it has been shown that NHP2 expression level was associated with prognosis in endometrial cancer [ 22 ]. Moreover, we also observed in a large dataset that high level of NHP2 was associated with poor outcome, in consistence with the fact that high NHP2 levels predict the lack of response to the Vistusertib + Anastrozole combination.…”

The roles of NOP56 in cancer and SCA36

“…However, the difference in NOP56 expression between endometrial cancer and healthy endometrial epithelium was not statistically significant. Using statistical methods, NOP56 was found to be significantly and positively correlated with telomere-associated protein TERF2 ( 70 ). In the whole blood mRNA gene expression of metastatic renal cell carcinoma, the increase of NOP56 was statistically significant ( 71 ).…”