Serum levels of 8-hydroxy-deoxyguanosine were positively correlated with ionizing radiation in non-small cell lung cancer, with possible prognostic significance in the squamous pathology subgroup in an observational study.
Ionizing radiation is associated with DNA damage, which can be direct or indirect, as with the production of reactive oxygen species (ROS). The most common ROS-induced base lesion is the addition of guanine and a hydroxyl group to the eighth position of the purine base, forming 8-hydroxy-deoxyguanosine (8-OHdG).
A study in the journal Biomedicines examined the 8-OHdG serum concentrations in a group of irradiated non-small cell lung cancer (NSCLC) patients, their correlation to radiation dose, and their potential prognostic value.
Patient Characteristics
The study comprised 52 NSCLC patients, of which 37 were males, who underwent loco-regional radiotherapy on primary tumor sites at stages IIIA to IIIC. The average patient age was 66.8 years. A total of 31% of patients had squamous histology, and 69% had non-squamous histology. All were smokers.
Plasma Concentrations of 8-OHdG Were Strongly Correlated With Irradiation Dose
All patients demonstrated a significant increase in the mean 8-OHdG plasma concentrations (p<0.01). A strong correlation was established between 8-OHdG increases and irradiation dose (correlation index r=0.975). Additionally, a significant increase was observed in 8-OHdG plasma concentrations in NSCLC with non-squamous histology, particularly after 20 Gy irradiation doses. Meanwhile, 8-OHdG plasma concentrations demonstrated an initial significant increase (p<0.01) after 10–15 Gy, followed by a significant decrease (p<0.01) after 20 Gy in NSCLC with squamous histology.
Differential Correlation of 8-OHdG Plasma Concentrations With Pretreatment Tumor Volume
The 8-OHdG plasma concentrations per cm3 of the pretreatment irradiated tumor volume were significantly higher (p<0.001) in patients with squamous than those with non-squamous histology. The mean 8-OHdG plasma concentrations demonstrated a much stronger correlation (r=0.92, p<0.001) with the pretreatment total irradiated tumor volume in patients with squamous histology, while no significant correlation was observed in those with non-squamous histology. In squamous NSCLC, 8-OHdG production was strongly correlated with the irradiated tumor volume per irradiation dose up to 20 Gy, but the correlation index decreased at doses higher than 25 Gy, likely due to the quicker tumor response. In non-squamous histology, a weak negative correlation was observed, which became higher at 30 Gy, suggesting higher 8-OHdG production from non-squamous tumors, disproportionate to their size, before and after irradiation.
Correlation Established Between 8-OHdG Concentration Changes and Tumor Response Rate
A very weak positive correlation was observed between post-radiotherapy 8-OHdG concentration changes and the tumor response rate status. The correlation was stronger in patients with squamous histology.
The correlations between the irradiated tumor volume per the respectively produced 8-OHdG concentrations at different irradiation doses and tumor response rates were strongly negative (r=−0.93 at 10 Gy, p<0.001) in patients with squamous histology but were positive (r=0.66 at 60 Gy, p<0.01) in patients with non-squamous histology, attributed to higher 8-OHdG production by these tumors. A very strong correlation was observed between the ratios of 8-OHdG concentrations to the respective pre-radiotherapy 8-OHdG concentrations and the corresponding tumor response rates at different irradiation doses in patients with squamous histology (p<0.001).
Histological Disparities in Irradiation Response and Predictive 8-OHdG Levels
The response rates of patients with non-squamous and squamous histology to irradiation were 58% and 68.7%, respectively. On plotting the 8-OHdG plasma concentration at a 10 Gy irradiation dose to the baseline (0 Gy), the area under the receiver operating characteristic curve value was 0.873 (95% confidence interval: 0.614–0.984), p<0.0001, with an associated criterion cutoff value of >1378 (sensitivity: 72.7%, specificity: 100%). When normalizing this ratio to body surface area, the area under the curve value was 0.927, p<0.0001, with an associated criterion cutoff value of >708 (sensitivity: 100%, specificity: 80%).
Levels of 8-OHdG CloselyCorrelated With the Development of Radiation-Induced Toxicities
Lastly, a very strong and significant positive correlation was established between the correlation coefficient (r) of 8-OHdG concentrations at different irradiation doses and the grade of irradiation-induced toxicities (r=0.98, p<0.01).
Source:
Orfanakos, K., Alifieris, C., Verigos, E. K., Deligiorgi, M. V., Verigos, K., Panayiotidis, M. I., Nikolaou, M., & Trafalis, D. T. (2024). The predictive value of 8-Hydroxy-Deoxyguanosine (8-OHDG) serum concentrations in irradiated Non-Small Cell Lung Carcinoma (NSCLC) patients. Biomedicines, 12(1), 134. https://doi.org/10.3390/biomedicines12010134
