Association of longer telomere length in cancer cells and cancer-associated fibroblasts with worse prognosis

Abstract

Background Telomere dysfunction has been reported to be directly involved in carcinogenesis owing to chromosomal instability and immortalization; however, the clinicopathological significance of telomeres remains controversial. We have shown that telomere shortening occurs in normal-appeared duct cells at the initiation and then progresses during the progression of pancreatic cancer. In this study, we determined the clinicopathological and prognostic value of telomere length (TL) in cancer progression. Methods TL in both cancer cells and cancer-associated fibroblasts (CAFs) was analyzed by high throughput quantitative fluorescence in situ hybridization (FISH) using a previously reported cohort comprising 1,434 cases of adenocarcinoma (ADC), squamous cell carcinoma (SCC), adenosquamous carcinoma (ASC), hepatocellular carcinoma (HCC), and renal cell carcinoma (RCC), which are known cancers with a significantly low incidence of alternative lengthening of telomeres. Cases were divided into two groups as follows: longer and shorter telomeres, according to the median TL of cancer cells and CAFs. The statistical significance of TL in cancer cells and CAFs on clinicopathological characteristics and prognosis were analyzed. Results There was a close association between TL in cancer cells and CAFs. Longer telomeres in cancer cells and CAFs were associated with aggressive features such as advanced stage, high mitosis score and nuclear score, poorly differentiated cancer, and desmoplastic stroma in ADC. Furthermore, a longer TL was an independent prognostic factor for ADC, SCC and RCC. Conclusion Longer telomeres are associated with worse prognosis in ADC, SCC and RCC. Thus, TL is a novel biomarker for the diagnosis of aggressive cancers with poor prognoses.

Correlation of Short Leukocyte Telomeres and Oxidative Stress with the Presence and Severity of Lung Cancer Explored by Principal Component Analysis

“…Furthermore, the telomere length is heritable to a significant extent (Samavat et al, 2021;Vaiserman and Krasnienkov, 2021). Contrary to the above-mentioned studies in which TL was measured in peripheral blood, a more recent study in which TL was measured in cancer cells and cancer-associated fibroblasts (CAFs) found longer telomeres to be associated with worse prognosis in adenocarcinoma and squamous cell carcinoma and acknowledged it as a novel biomarker for the diagnosis of aggressive cancers with poor prognoses (Matsuda et al, 2023). In studies exploring the role of cancer cell telomere length in cancer risk, both shorter and longer telomere lengths have been found to be associated with increased cancer risk (Chen et al, 2014), the possible explanation of the latter suggested to be lying in the germline mutations of the telomere maintenance genes causing telomerase up-regulation (Chen et al, 2014).…”

Epistemology of the Origin of Cancer II: Fibroblasts Are the First Cells to Undergo Neoplastic Transformation

“…CAFs have also been identified in precancerous lesions of the blood, for example, monoclonal gammopathy of unknown significance [181][182][183] and the breast. Tenascin, which is a marker for CAFs [184], has also been detected in precancerous breast lesions as well as in ductal or lobular carcinoma in situ [185][186][187][188][189][190][191][192][193].…”

High expression of RTEL1 predicates worse progression in gliomas and promotes tumorigenesis through JNK/ELK1 cascade

“…In addition, telomere length was found significantly shortened in chronic myeloid leukemia [ 6 ]. However, in most solid tumors such as glioma [ 7 ], lung adenocarcinoma [ 8 ], neuroblastoma [ 9 ], bladder cancer [ 10 ], melanoma [ 11 , 12 ], hepatocellular carcinoma [ 13 ], and kidney cancer [ 14 ], the telomere length was increased compared with normal tissues [ 15 – 18 ].…”