The dynamics of telomere length in primary and metastatic colorectal cancer lesions

Abstract

Telomeric sequences, the structures comprised of hexanucleotide repeats and associated proteins, play a pivotal role in chromosome end protection and preservation of genomic stability. Herein we address telomere length (TL) dynamics in primary colorectal cancer (CRC) tumour tissues and corresponding liver metastases. TL was measured by multiplex monochrome real-time qPCR in paired samples of primary tumours and liver metastases along with non-cancerous reference tissues obtained from 51 patients diagnosed with metastatic CRC. Telomere shortening was observed in the majority of primary tumour tissues compared to non-cancerous mucosa (84.1%, p < 0.0001). Tumours located within the proximal colon had shorter TL than those in the rectum (p < 0.05). TL in liver metastases was not significantly different from that in primary tumours (p = 0.41). TL in metastatic tissue was shorter in the patients diagnosed with metachronous liver metastases than in those diagnosed with synchronous liver metastases (p = 0.03). The metastatic liver lesions size correlated with the TL in metastases (p < 0.05). Following the neoadjuvant treatment, the patients with rectal cancer had shortened telomeres in tumour tissue than prior to the therapy (p = 0.01). Patients with a TL ratio between tumour tissue and the adjacent non-cancerous mucosa of ≥ 0.387 were associated with increased overall survival (p = 0.01). This study provides insights into TL dynamics during progression of the disease. The results show TL differences in metastatic lesions and may help in clinical practice to predict the patient’s prognosis.

Current and Future Trends of Colorectal Cancer Treatment: Exploring Advances in Immunotherapy

“…Furthermore, TL has emerged as a potential predictive biomarker for the clinical outcome of anti-EGFR monoclonal antibody therapy in patients with KRAS wild-type metastatic CRC. Therefore, investigations are underway to determine whether mutations in the KRAS oncogene impact telomere deregulation [ 21 , 24 , 27 , 29 , 133 ].…”

“…In contrast to ICIs that greatly exert their action through antagonism of suppressor T-cell receptors, ACT providesits anticarcinogenic effect through isolating the expansion of a great volume of T cells that may overcome certain suppressive immunomodulatory parameters [ 19 ]. Current research in CRC epigenetics highlights the important role of telomeres and their regulating enzyme, telomerase, not only as clinical biomarkers but also as potential therapeutic targets [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. However, it is also well established that immune responses may be negatively affected in cases of telomere attrition [ 27 , 28 ].…”