Telomere in colorectal cancer associated with distant metastases and predicted a poor prognosis

Ye, Xiaorong; Li, Jianjiong; Song, Chenjun; Chen, Wenbin

doi:10.21037/tcr-20-3341

Cited by 5 publications

(5 citation statements)

References 35 publications

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“…We confirmed that primary CRC tissue exhibits shorter TL compared to non-cancerous reference mucosa, which has been previously described by us and many other studies 13 , 17 , 22 – 26 . This phenomenon strongly supports the notion that the telomere crisis might be one of the pivotal events in the disease development 24 .…”

Section: Discussionsupporting

confidence: 92%

“…Our result is in agreement with Le Balc’h et al who also did not find any association between TL in tumours of patients with CRC and the presence or absence of distant metastasis at the time of diagnosis 17 . However, in a study by Ye et al patients diagnosed with advanced CRC with distant metastases had shorter telomeres in primary tumours compared to those of non-metastatic patients 22 .…”

Section: Discussionmentioning

confidence: 90%

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

Kroupa

Kubeček

Tomášová

et al. 2023

Sci Rep

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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.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 90%

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

Kroupa

Kubeček

Tomášová

et al. 2023

Sci Rep

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“…Clinically, there has been much interest in telomere length and telomerase activity and its association with malignant transformation (90,91). Several studies indicated that CRCs display shorter telomeres when compared with the surrounding mucosa, especially in distant metastases (92)(93)(94). Telomere shortening can be accelerated by oxidative stress due to 8-oxoguanine formation at telomeres (95,96).…”

Section: Discussionmentioning

confidence: 99%

Deficiency in mammalian STN1 promotes colon cancer development via inhibiting DNA repair

Nguyễn

Kim

et al. 2023

Sci. Adv.

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Despite the high lethality of colorectal cancers (CRCs), only a limited number of genetic risk factors are identified. The mammalian ssDNA-binding protein complex CTC1-STN1-TEN1 protects genome stability, yet its role in tumorigenesis is unknown. Here, we show that attenuated CTC1/STN1 expression is common in CRCs. We generated an inducible STN1 knockout mouse model and found that STN1 deficiency in young adult mice increased CRC incidence, tumor size, and tumor load. CRC tumors exhibited enhanced proliferation, reduced apoptosis, and elevated DNA damage and replication stress. We found that STN1 deficiency down-regulated multiple DNA glycosylases, resulting in defective base excision repair (BER) and accumulation of oxidative damage. Collectively, this study identifies STN1 deficiency as a risk factor for CRC and implicates the previously unknown STN1-BER axis in protecting colon tissues from oxidative damage, therefore providing insights into the CRC tumor–suppressing mechanism.

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“…Telomere length in cancer tissue was substantially shorter than in normal mucosa. Advanced CRC (stage II-IV) cancers have longer telomeres than stage I tumors (Ye et al, 2021). According to Taheri et al (2022), CRC tissue had reduced hTERT expression levels.…”

Section: Telomerasementioning

confidence: 99%

Novel biomarkers used for early diagnosis and tyrosine kinase inhibitors as targeted therapies in colorectal cancer

Jiang,

Zhou,

2023

Front. Pharmacol.

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Colorectal cancer (CRC) is the third most common and second most lethal type of cancer worldwide, presenting major health risks as well as economic costs to both people and society. CRC survival chances are significantly higher if the cancer is diagnosed and treated early. With the development of molecular biology, numerous initiatives have been undertaken to identify novel biomarkers for the early diagnosis of CRC. Pathological disorders can be diagnosed at a lower cost with the help of biomarkers, which can be detected in stool, blood, and tissue samples. Several lines of evidence suggest that the gut microbiota could be used as a biomarker for CRC screening and treatment. CRC treatment choices include surgical resection, chemotherapy, immunotherapy, gene therapy, and combination therapies. Targeted therapies are a relatively new and promising modality of treatment that has been shown to increase patients’ overall survival (OS) rates and can inhibit cancer cell development. Several small-molecule tyrosine kinase inhibitors (TKIs) are being investigated as potential treatments due to our increasing awareness of CRC’s molecular causes and oncogenic signaling. These compounds may inhibit critical enzymes in controlling signaling pathways, which are crucial for CRC cells’ development, differentiation, proliferation, and survival. On the other hand, only one of the approximately 42 TKIs that demonstrated anti-tumor effects in pre-clinical studies has been licensed for clinical usage in CRC. A significant knowledge gap exists when bringing these tailored medicines into the clinic. As a result, the emphasis of this review is placed on recently discovered biomarkers for early diagnosis as well as tyrosine kinase inhibitors as possible therapy options for CRC.

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Telomere in colorectal cancer associated with distant metastases and predicted a poor prognosis

Cited by 5 publications

References 35 publications

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

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

Deficiency in mammalian STN1 promotes colon cancer development via inhibiting DNA repair

Novel biomarkers used for early diagnosis and tyrosine kinase inhibitors as targeted therapies in colorectal cancer

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