Dataset Information

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-appearing duct cells at initiation and then continues 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 using a previously reported cohort comprising 1434 cases of adenocarcinoma (ADC), squamous cell carcinoma (SCC), adenosquamous carcinoma, hepatocellular carcinoma, and renal cell carcinoma (RCC), which are known cancers with a statistically significantly low incidence of alternative lengthening of telomeres. Cases were divided into 2 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 was 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.

Conclusions

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.

SUBMITTER: Matsuda Y

PROVIDER: S-EPMC9905972 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Publications

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

Matsuda Yoko Y Ye Juanjuan J Yamakawa Keiko K Mukai Yuri Y Azuma Kazuki K Wu Linxuan L Masutomi Kenkichi K Yamashita Taro T Daigo Yataro Y Miyagi Yohei Y Yokose Tomoyuki T Oshima Takashi T Ito Hiroyuki H Morinaga Soichiro S Kishida Takeshi T Minamoto Toshinari T Kojima Motohiro M Kaneko Shuichi S Haba Reiji R Kontani Keiichi K Kanaji Nobuhiro N Okano Keiichi K Muto-Ishizuka Mariko M Yokohira Masanao M Saoo Kousuke K Imaida Katsumi K Suizu Futoshi F

Journal of the National Cancer Institute 20230201 2

<h4>Background</h4>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-appearing duct cells at initiation and then continues during the progression of pancreatic cancer. In this study, we determined the clinicopathological and prognostic value of telomere length (TL) in cancer p ...[more]

PMID: 36567450

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Project description:BackgroundTelomeres are essential for chromosomal integrity and stability. Shortened telomere length (TL) has been associated with risk of cancers and aging-related diseases. Several studies have explored associations between TL and cancer prognosis, but the results are conflicting.MethodsProspective studies on the relationship between TL and cancer survival were identified by a search of PubMed up to May 25, 2015. There were no restrictions on the cancer type or DNA source. The quality of the included studies was assessed using the Newcastle-Ottawa Scale. Meta-analysis approaches were conducted to determine pooled relative risks and 95% confidence intervals.ResultsThirty-three articles containing forty-five independent studies were ultimately involved in our meta-analysis, of which twenty-seven were about overall cancer survival and eighteen were about cancer progression. Short TL was associated with increased cancer mortality risk (RR = 1.30, 95%CI: 1.06-1.59) and poor cancer progression (RR = 1.44, 95%CI: 1.10-1.88), both with high levels of heterogeneity (I2 = 83.5%, P = 0.012for overall survival and I2 = 75.4%, P = 0.008 for progression). TL was an independent predictor of overall cancer survival and progression in chronic lymphocytic leukemia. Besides, short telomeres were also associated with increased colorectal cancer mortality and decreased overall survival of esophageal cancer, but not in other cancers. Cancer progression was associated with TL in Asian and America populations and short TL predicted poor cancer survival in older populations. Compared with tumor tissue cells, TL in blood lymphocyte cells was better for prediction. In addition, the associations remained significant when restricted to studies with adjustments for age, with larger sample sizes, measuring TL using southern blotting or estimating risk effects by hazard ratios.ConclusionShort TL demonstrated a significant association with poor cancer survival, suggesting the potential prognostic significance of TL. Additional large well-designed studies are needed to confirm our findings.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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