Search for new clinical biomarkers targets in prostate cancer (PC) is urgent. Telomeres might be one of these targets. Telomeres are the extremities of linear chromosomes, essential for genome stability and control of cell divisions. Telomere homeostasis relies on the proper functioning of shelterin and CST complexes. Telomeric dysfunction and abnormal expression of its components are reported in most cancers and are associated with PC. Despite this, there are only a few studies about the expression of the main telomere complexes and their relationship with PC progression. We aimed to evaluate the role of shelterin (POT1, TRF2, TPP1, TIN2, and RAP1) and CST (CTC1, STN1, and TEN1) genes and telomere length in the progression of PC. We evaluated genetic alterations of shelterin and CST by bioinformatics in samples of localized ( = 499) and metastatic castration-resistant PC ( = 444). We also analyzed the expression of the genes using TCGA (localized PC = 497 and control = 152) and experimental approaches, with surgical specimens (localized PC = 81 and BPH = 10) and metastatic cell lines (LNCaP, DU145, PC3 and PNT2 as control) by real-time PCR. Real-time PCR also determined the telomere length in the same experimental samples. All acquired data were associated with clinical parameters. Genetic alterations are uncommon in PC, but POT1, TIN2, and TEN1 showed significantly more amplifications in the metastatic cancer. Except for CTC1 and TEN1, which are differentially expressed in localized PC samples, we did not detect an expression pattern relative to control and cell lines. Nevertheless, except for TEN1, the upregulation of all genes is associated with a worse prognosis in localized PC. We also found that increased telomere length is associated with disease aggressiveness in localized PC. The upregulation of shelterin and CST genes creates an environment that favors telomere elongation, giving selective advantages for localized PC cells to progress to more aggressive stages of the disease.

中文翻译：

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Shelterin 和 CST 基因的上调以及更长的端粒与前列腺癌的不良预后特征相关

寻找前列腺癌（PC）新的临床生物标志物靶点刻不容缓。端粒可能是这些目标之一。端粒是线性染色体的末端，对于基因组稳定性和细胞分裂的控制至关重要。端粒稳态依赖于庇护蛋白和 CST 复合物的正常功能。据报道，大多数癌症都存在端粒功能障碍及其成分的异常表达，并且与 PC 相关。尽管如此，关于主要端粒复合物的表达及其与 PC 进展的关系的研究却很少。我们的目的是评估庇护蛋白（POT1、TRF2、TPP1、TIN2 和 RAP1）和 CST（CTC1、STN1 和 TEN1）基因以及端粒长度在 PC 进展中的作用。我们通过生物信息学评估了局部 (= 499) 和转移性去势抵抗性 PC (= 444) 样本中的庇护蛋白和 CST 的遗传改变。我们还使用 TCGA（局部 PC = 497 和对照 = 152）和实验方法分析了基因的表达，其中手术标本（局部 PC = 81 和 BPH = 10）和转移细胞系（LNCaP、DU145、PC3 和 PNT2 为控制）通过实时PCR。实时 PCR 还测定了相同实验样本中的端粒长度。所有获得的数据都与临床参数相关。遗传改变在 PC 中并不常见，但 POT1、TIN2 和 TEN1 在转移性癌症中显示出显着更多的扩增。除了在局部 PC 样本中差异表达的 CTC1 和 TEN1 之外，我们没有检测到相对于对照和细胞系的表达模式。然而，除了TEN1之外，所有基因的上调都与局限性PC的较差预后相关。我们还发现端粒长度的增加与局部 PC 的疾病侵袭性相关。 Shelterin 和 CST 基因的上调创造了一个有利于端粒延长的环境，为局部 PC 细胞提供了选择性优势，使其进展到疾病的更具侵袭性的阶段。