Genetic Variants of the TERT Gene, Telomere Length, and Circulating TERT as Prognostic Markers in Rectal Cancer Patients

Abstract

Single-nucleotide polymorphisms (SNPs) in the TERT gene can affect telomere length and TERT expression and have been associated with risk and/or outcome for several tumors, but very few data are available about their impact on rectal cancer. Eight SNPs (rs2736108, rs2735940, rs2736098, rs2736100, rs35241335, rs11742908, rs2736122 and rs2853690), mapping in regulatory and coding regions of the TERT gene, were studied in 194 rectal cancer patients to evaluate their association with constitutive telomere length, circulating TERT mRNA levels, response to neoadjuvant chemoradiotherapy (CRT) and disease outcome. At diagnosis, the rs2736100CC genotype was associated with longer telomeres measured pre-CRT, while the rs2736100CC, rs2736108TT and rs2735940AA were associated with greater telomere erosion evaluated post-CRT. The rs2736108CC and rs2853690AA/GG genotypes, respectively associated with lower telomere erosion and lower levels of circulating TERT post-CRT, were also independently associated with a better response to therapy [OR 4.6(1.1–19.1) and 3.0(1.3–6.9)]. Overall, post-CRT, low levels (≤ median value) of circulating TERT and its stable/decreasing levels compared to those pre-CRT, were independently associated with a better response to therapy [OR 5.8(1.9–17.8) and 5.3(1.4–19.4), respectively]. Furthermore, post-CRT, patients with long telomeres (>median value) and low levels of circulating TERT had a significantly lower risk of disease progression [HR 0.4(0.1–0.9) and 0.3(0.1–0.8), respectively]. These findings suggest that TERT SNPs could be a useful tool for improving the selection of patients who could benefit from CRT and support the role of telomere length and circulating TERT mRNA levels as useful markers for monitoring the response to therapy and disease outcome in rectal cancer patients.

Biological Predictors of De Novo Tumors in Solid Organ Transplanted Patients During Oncological Surveillance: Potential Role of Circulating TERT mRNA

“…Importantly, several studies have been demonstrated that circulating TERT mRNA is an independent prognostic marker in different types of tumors ( 35 ), including gastric ( 48 ), prostatic ( 49 ), lung ( 50 ), and colorectal cancers ( 38 , 46 , 51 ). In addition, TERT mRNA levels in plasma samples of patients with rectal cancer were identified as a predictive marker of response to therapy ( 38 , 39 , 51 ). In the present study, we found that patients of the T cohort showed significantly higher levels of circulating TERT mRNA than those of the NT cohort both at baseline and follow-up.…”

“…RNA was extracted from plasma samples as previously described ( 38 , 39 ), using 1 mL instead of 500 μL of plasma and reagents’ quantities adjusted accordingly. RNA was reverse transcribed into cDNA using the SuperScript TM III RNase reverse transcriptase assay (Thermo Fisher Scientific) in a final volume of 80 μL, according to the manufacturer’s instructions.…”

Immune Activation, Exhaustion and Senescence Profiles as Possible Predictors of Cancer in Liver Transplanted Patients

“…DNA was extracted from PBMC, using QIAmp DNA Blood Mini Kit (Qiagen, Hilden, Germany) according to the manufacturer’s instructions. Relative telomere length (RTL) was determined by monochrome quantitative multiplex real-time PCR, as previously described ( 20 , 21 ).…”

Biomarkers for Predicting the Response to Radiation-Based Neoadjuvant Therapy in Rectal Cancer

“…The TG genotype was more likely to result in complete response (CR) (p = 0.02). Rampazzo et al [33] analysed 8 SNPs (rs11742908, rs2736108, rs2736098, rs2736100, rs2736122, rs2735940, rs2853690 and rs35241335) located in the regulatory and coding regions of the telomerase reverse transcriptase (TERT) gene. Their results showed the rs2853690AA/GG and rs2736108CC genotypes were associated with less telomere erosion and lower levels of circulating TERT following nCRT.…”