Abstract
Outside a few affluent countries with adequate vaccination and screening coverage, cervical cancer remains the leading cause of cancer-related deaths in women in many countries. Currently, a major problem is that a substantial proportion of patients are already at an advanced cancer stage when diagnosed. There is increasing evidence that indicates the involvement of translationally controlled tumor protein 1 (TPT1) overexpression in cancer development, but little is known about its implication in cervical cancer. We assessed the levels of TPT1 in surgical tissue and sera of patients with cervicitis, cervical intraepithelial neoplasia III, and cervical cancer, as well as in normal and cancerous cervical cell lines. Gene sets, pathways, and functional protein interactions associated with TPT1 were identified using the TCGA data cohort of cervical cancer. We found that the TPT1 expression was significantly increased in cervical cancer tissue compared to all nonmalignant cervical tissues, including samples of cervicitis, cervical intraepithelial neoplasia III, and normal controls. Serum level of TPT1 was also increased in cervical cancer patients compared to healthy subjects. Furthermore, elevated TPT1 expression was significantly correlated with lymph node metastasis and a low differentiation degree of the cancer. In the cancerous tissues and cell lines, selective markers of PI3K/AKT/mTOR pathway over-activation, apoptosis repression, and EMT were detected, and their interaction with TPT1 was supported by biometrics analyses. Our results, for the first time, demonstrate a strong correlation of upregulated TPT1 expression with cervical cancer progression, suggesting that TPT1 might provide a potential biomarker for cervical cancer progression.
Highlights
Controlled tumor protein 1 (TPT1/TCTP, aka histamine-releasing factor HRF and fortilin) is a highly conserved protein abundantly present in all eukaryotic organisms (Li et al, 2001) and is involved in almost all fundamental biological processes underpinning growth, stress response, and survival (Bommer and Telerman, 2020)
We found that the TPT1 protein abundance was almost doubled in the cancerous tissues compared to the paired paracancerous tissues (Figure 1A)
The TPT1 gene transciption was remarkably upregulated in cervical cancer cell lines (Figure 1D)
Summary
Controlled tumor protein 1 (TPT1/TCTP, aka histamine-releasing factor HRF and fortilin) is a highly conserved protein abundantly present in all eukaryotic organisms (Li et al, 2001) and is involved in almost all fundamental biological processes underpinning growth, stress response, and survival (Bommer and Telerman, 2020). TPT1 overexpression in circulation or tissues of patients has been documented in leukemia (Yağcı et al, 2013) and cancers in most main human organs such as the lung (Chen et al, 2013; Sun et al, 2019), liver (Chan et al, 2012; Lin et al, 2020), colon (Bommer et al, 2017), prostate (Kaarbø et al, 2013; Rocca et al, 2015), breast (Neuhäuser et al, 2019), etc. The TPT1 gene was identified as the most differentially downregulated in revertant human leukemia cell U937 and breast cancer cells such as MCF7, compared with their malignant counterparts (Tuynder et al, 2002). Inhibition of TPT1 by anti-sense cDNA or siRNA in vitro or injection of antagonistic drugs, such as anti-histaminic compounds into tumor-bearing mice, suppressed the malignant phenotype of cancers of the breast, lung, and colon and melanoma (Tuynder et al, 2004). By analyzing both tissue and serum TPT1 levels from clinical subjects and online databases, we attempt to clarify the relevance of TPT1 to cervical cancer development and the potential value of serum TPT1 as a facile indicator of cancer diagnosis and prognosis
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