<p>Telomere Length in Renal Cell Carcinoma: The Jekyll and Hyde Biomarker of Ageing of the Kidney</p>

Abstract

Renal cell carcinoma (RCC) is a heterogeneous group of cancers where the clear cell (ccRCC) is the most common and the most lethal. The absence of accurate diagnostic and follow-up biomarkers along with the time-limited response to therapies may explain the lethality and shows the necessity of new sensitive and specific biomarkers. One of the most studied molecules are the telomeres: specialized ribonucleoprotein structures that keep the structural integrity of the genome. Among other features, telomere length (TL) has been widely studied in several tumor models regarding its biomarker potential, due to the easy detection and quantification. The scope of this review was to analyze all the information about this parameter in RCC. There was some disparity in the results of the studies, since some pointed to an association between short TL and risk or poor outcome of RCC; others between long TL and RCC outcome and some did not find any association. We propose some epidemiological and biological explanations to these differences. The telomeres may play a dual role during RCC carcinogenesis in the early stages, short telomeres may increase RCC risk and in late carcinogenesis, long telomeres seem to be associated with tumor prognosis. However, the controversy of the results along with the lack of specificity are some problems that need to be clarified for the usage of TL as a prognostic biomarker.

Shorter Leukocyte Telomere Length Is Associated with Worse Survival of Patients with Bladder Cancer and Renal Cell Carcinoma

“…The reason for this discrepancy may be differences in cohort sizes and tumor stages. Of note, Morais and colleagues suggested that TL may have a dual role in RCC, specifically that short TL could increase RCC risk and cancer progression in late carcinogenesis, while long telomeres may be associated with tumor prognosis in early stages [85]. The relationship between PBL TL and RCC risk and the survival of patients with RCC still remains to be further clarified in future studies.…”

Does Subtelomeric Position of COMMD5 Influence Cancer Progression?

“…Thus, the association between telomere length and the risk of cancer remains conflicting and these observations suggest that telomeres may play diverse roles in different type of cancers. In renal cancer, Morais et al proposed that telomeres may play a dual role during RCC carcinogenesis; in the early stages, short telomeres may increase RCC risk and in late carcinogenesis, long telomeres seem to be associated with bad tumor prognosis ( 71 ). Using a large series of colorectal cancers, Rampazzo et al demonstrated that telomere length varies not only with tumor stage but also differs according to tumor location, being longer in rectal cancers ( p = 0.03) ( 78 ).…”

Roles of telomeres and telomerase in age‑related renal diseases (Review)

“…As RCCs are often diagnosed at an advanced stage, patients with RCC have a poor survival rate, <8% ( 30 ). TL is known to gradually shorten with age, which may lead to chromosomal instability and subsequent tumorigenesis ( 31 ). While some previous studies have demonstrated that a shortened TL promoted poor outcomes for patients with RCC ( 32 ), others studies have failed to elucidate such a relationship ( 33 , 34 ).…”

“…While some previous studies have demonstrated that a shortened TL promoted poor outcomes for patients with RCC ( 32 ), others studies have failed to elucidate such a relationship ( 33 , 34 ). However, Morais and Dias ( 31 ) suggested that TL may serve a dual role in RCC, for instance, short telomere length can increase RCC risk in late carcinogenesis, while long telomere length appears to be associated with tumor prognosis in the early stages. Therefore, an increasing number of researchers have also investigated methods, such as reverse transcription PCR, TRF-Southern blotting and fluorescence in situ hybridization, for measuring TL to predict the survival of patients with RCC ( 4 , 35 , 36 ).…”