AI Article Synopsis
- Continuous oxidative stress (OS) contributes to the worsening of chronic liver diseases and cancer progression by shortening telomeres in liver cells, though its exact effects on human liver cancer (HCC) are still unclear.
- The study analyzed oxidative stress levels, telomere lengths, and telomerase activity in 68 HCC samples, finding that higher OS grades correlated with shorter telomeres and increased telomerase activity.
- Results indicate that in HCC, high OS promotes cancer cell proliferation and reduces apoptosis, linking OS to poor cancer prognosis and suggesting its potential as a clinical assessment marker for HCC.
Article Abstract
Background/aims: Continuous oxidative stress (OS) plays an important role in the progression of chronic liver diseases and hepatocarcinogenesis through telomere shortening in hepatocytes. However, it has not been established how the OS influences the progression of human hepatocellular carcinomas (HCCs). We examined the correlations of OS with telomere length of cancer cells, telomerase activity and other clinicopathological factors in 68 HCCs.
Methods: The level of 8-hydroxy-2'-deoxyguanosine (8-OHdG) as a marker of OS was examined immunohistochemically and OS was scored in four grades (0-3). The telomere length of cancer cells was measured by quantitative fluorescence in situ hybridization. Telomerase activity was measured by (i) immunodetection of human telomerase reverse transcriptase (hTERT) and (ii) telomere repeat amplification protocol (TRAP) assay. Telomerase related proteins, phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and Akt, and other clinicopathological factors were also evaluated.
Results: As the OS grade increased, the average telomere length became significantly shorter in HCCs, especially in the hTERT-negative group. In the state of high-grade OS, hTERT-positive HCC cells showed more proliferative and less apoptotic features compared with hTERT-negative HCC cells. Telomerase activity, as measured by the TRAP assay, was strongly correlated with OS grade in HCCs. Furthermore, a high OS grade was correlated with the downexpression of PTEN and the activation of Akt.
Conclusions: Oxidative stress enhanced the malignant potential of HCCs through the activation of telomerase, which raises the possibility of using OS as a marker for assessing the clinical state of HCCs.
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| http://dx.doi.org/10.1111/j.1478-3231.2008.01963.x | DOI Listing |
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