Yes-associated protein 1 (YAP1) expression and nuclear localization have been found to be increased in various cancers [1−4]. YAP1 is one of the most important effectors of the Hippo signaling pathway and is involved in crosstalk with other cancer-promoting pathways. The Hippo pathway plays a crucial role in organ size control and tissue regeneration [5]. The roles of Hippo pathway dysregulation in tumorigenesis and cancer progression have been widely reported [6]. As a potent oncogene activated in many cancers, YAP1 has a negatively regulated downstream target in the Hippo signaling pathway and functions as a transcriptional coactivator involved in the regulation of cell growth, proliferation, and apoptosis [2,7−9]. YAP1 plays a key role as a tumor suppressor in the Hippo signaling pathway and enhances gene transcription by binding to transcription factors [10]. Specifically, YAP1 contributes to cancer development by promoting malignant phenotypes, the expansion of cancer stem cells, and drug resistance of cancer cells. YAP1 is considered a potent oncogene closely linked to the progression of several cancer types [11,12], and YAP1 overexpression in cancer cell lines can also promote tumor growth [13,14]. Therefore, YAP1 promotes tumorigenesis, but the underlying mechanisms by which YAP1 exerts this effect require further exploration.

Telomeres are cellular nucleoprotein complexes, and their main function is to maintain chromosomal integrity and genomic stability [15]. A telomere is a ribonucleoprotein complex composed of 2 main core subunits: telomerase reverse transcriptase (TERT), which constitutes the catalytic subunit, and a functional telomerase RNA component (TR or TERC) that provides a template for telomerase elongation [16]. A positive correlation between TERT mRNA levels and telomerase activity has been reported, suggesting that telomerase is primarily regulated by TERT expression [17]. Telomerase is active in adult germ-line tissues, immortal cells [18], and most malignant tumors [19]. TERT induces stemness of cancer cells to promote metastasis and recurrence [20]. In cancer cells, the upregulation of TERT transcriptional activity has been reported [21]. TERT overexpression has been detected in more than 80% to 90% of human cancers [15]. Thus, TERT overexpression may represent the mechanism by which cancer cells prevent telomere shortening and become immortal [22]. Zhang et al. [23] recently reported that YAP1 regulates TERT expression, and that hyperactivation of YAP1 promotes telomerase activity and increases telomeric length, causing an increase in TERT expression. They also showed that TERT expression was positively correlated with YAP1 activation in liver cancer tissues. Several studies have reported that TERT overexpression contributes to cancer progression [24]. Therefore, YAP1 promotes TERT expression, which may contribute to tumor progression [25]. However, several studies have highlighted the importance of TERC in cancer because of findings indicating that TERC expression may be highly upregulated in a variety of cancers [26−30]. Although TERC is associated with the development of several diseases, its underlying mechanisms in cancer are poorly understood. In addition, the correlation between the expression of YAP1 and telomerase-associated genes in cancer has not been completely explored.

In the present study, we analyzed YAP1 expression in normal and different types of tumor tissues based on The Cancer Genome Atlas (TCGA) data using online databases and tools. We also evaluated the prognostic value of YAP1 expression its correlation with the expression of 2 major telomerase components (TERT and TERC) in various cancer types on the basis of TCGA data.

In the past decade, previous studies have focused on determining YAP1 expression to improve the understanding of its prognostic significance and potential effect on various cancer types. YAP1 is a potent oncogene [24], and its levels are frequently increased in many cancer types [1,14,36−38]. The expression and role of YAP1 in cancer are cell type-dependent, and its expression may contribute to cancer development [2,6,9,39]. Upregulation of YAP1 expression has been observed in multiple cancer types. YAP1 overexpression has been reported in patients with hepatocellular carcinoma (HCC), colorectal cancers, LUAD, ovarian cancer, and prostate cancer [2,3,14,40]. These findings suggest the potential oncogenic role of YAP1 in multiple cancer types.

Zhang et al. [41] performed the immunohistochemical analyzes of primary esophageal squamous cell carcinoma tumor resection samples from patients, and reported that overexpression of YAP1 was associated with tumor relative to adjacent tissue samples. In addition, Collak et al. [42] identified overexpression of YAP1 in nuclear and cytosolic of benign prostates using immunohistochemistry, whereas moderate expression of YAP1 was found in cellular locations of prostate intraepithelial neoplasia and prostate cancer. These findings show differences in expression levels of YAP1 across cancer tissue samples, and are consistent with those presented in this study.

In this study, we showed that the prognostic value of YAP1 expression was significant in various cancer types. Importantly, our data provide evidence that YAP1 expression is correlated with telomerase (TERT and TERC) expression in various cancer types. Previous studies have reported that YAP1 is a prognostic marker for OS and DFS in HCC [2]. YAP1 expression is a remarkable predictor of poor prognosis in HCC patients with negative keratin 19 cells [9]. YAP1 expression has also been significantly correlated with a poor prognosis in OV [6,36,43,44]. However, our results showed that YAP1 expression did not have a prognostic role in various cancers, including HCC and OSC, based on TCGA data. Interestingly, higher expression of YAP1 predicted poorer OS in patients with ACC and PAAD, and poorer DFS in patients with ACC and BLCA. According to these results, we suggest that higher expression of YAP1 may be significantly correlated to a poorer prognosis in various cancers.

Telomerase is active in adult germ-line tissues, immortal cells [18], and most types of malignant tumors [19]. It is upregulated during tumorigenesis through the transcriptional regulation of TERT in up to 90% of cancers [45−48]. Upregulation of TERC is an early event in tumorigenesis, and TERC could be more closely correlated with tumor grade than telomerase activity or TERT expression [49−55]. TERC activity is associated with cancer, but its underlying mechanisms are poorly understood. This is the first study to explore the correlations between YAP1 expression and telomerase expression (TERT and TERC) in various cancer types. Our data indicated that YAP1 expression was negatively correlated with TERT in BLCA, BRCA, CHOL, COAD, LGG, MESO, PRAD, READ, SARC, TGCT, THCA, and THYM. YAP1 expression was positively correlated with TERT in OV and UVM, but negatively correlated with TERC in BLCA, BRCA, DLBC, GBM, HNSC, LIHC, LUSC, MESO, OV, PRAD, READ, TGCT, and THYM. Our findings may suggest that YAP1 expression affects TERT and TERC expression in different cancer types. However, further investigation should be performed to elucidate the potential role of YAP1 and telomere-related gene expression, which may contribute to novel research and therapies for treating various cancer types. Our results indicate that YAP1 expression is correlated with 2 major components of telomerase, and is associated with a poor prognosis in various cancer types.

In this study, we attempted to confirm the clinical value of YAP1 expression in various cancer types and its effect on telomerase. Although YAP1 expression was different in many cancer types, the detailed mechanism underlying YAP1 regulation should be established in future studies.

We suggest that YAP1 could be a potential prognostic biomarker, which may stimulate novel cancer research. Understanding the correlation between YAP1 expression and telomerase may provide insights into telomere-related diseases, including different types of cancers. Therefore, future oncology research could seek to understand the biological functions of YAP1 and the correlation between YAP1 and telomere-associated gene expression.