Toapichattrakul Piyapasara, Autsavapromporn Narongchai, Duangya Aphidet, Pojchamarnwiputh Suwalee, Nachiangmai Wittanee, Kittidachanan Kittikun, Chakrabandhu Somvilai
Division of Radiation Oncology, Department of Radiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
Division of Diagnostic Radiology, Department of Radiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
J Gastrointest Oncol. 2024 Oct 31;15(5):2117-2128. doi: 10.21037/jgo-24-488. Epub 2024 Oct 29.
The most detrimental effect of DNA damage from radiation is DNA double-strand breaks, making it critical to identify reliable biomarkers for treatment response in cancer therapy. Gamma-H2AX (γ-H2AX), a marker of DNA double-strand breaks, was evaluated in this study as a potential biomarker for treatment response in locally advanced rectal cancer patients undergoing preoperative concurrent chemoradiation (CCRT).
Thirty patients with locally advanced rectal cancer received preoperative CCRT. Peripheral blood mononuclear cells (PBMCs) were collected at five time points: baseline, 24 hours after the first radiation fraction, mid-treatment, end of treatment, and six weeks post-CCRT. γ-H2AX levels were measured in these samples. MRI was used to assess treatment response based on magnetic resonance tumor regression grade (mrTRG). Patients were classified as responders or non-responders based on mrTRG. -test and repeated measures analysis of variance (ANOVA) evaluated dynamic changes in γ-H2AX levels, and a multilevel linear regression model analyzed the relationship between γ-H2AX levels and treatment response.
Nineteen out of thirty patients (63.33%) were classified as responders. Significant dynamic changes in γ-H2AX levels were observed between non-responders and responders (P=0.01). The multilevel linear regression model showed a trend towards increased γ-H2AX levels in responders [1.17, 95% confidence interval (CI): -0.02 to 2.34, P=0.053]. Significant differences in γ-H2AX levels were observed from baseline to mid-treatment, end of treatment, and six weeks post-CCRT. Pathologic complete response (pCR) after CCRT was associated with significantly higher γ-H2AX ratios compared to those without pCR (P=0.04). However, no significant difference was identified in the multilevel linear regression model.
γ-H2AX may have potential as a biomarker for treatment response in locally advanced rectal cancer patients undergoing preoperative CCRT, although further validation is required.
辐射造成的DNA损伤最有害的影响是DNA双链断裂，因此在癌症治疗中识别可靠的治疗反应生物标志物至关重要。本研究评估了γ-H2AX（一种DNA双链断裂标志物）作为接受术前同步放化疗（CCRT）的局部晚期直肠癌患者治疗反应潜在生物标志物的可能性。
30例局部晚期直肠癌患者接受术前CCRT。在五个时间点采集外周血单个核细胞（PBMC）：基线、首次放疗后24小时、治疗中期、治疗结束时以及CCRT后六周。检测这些样本中的γ-H2AX水平。采用磁共振成像（MRI）根据磁共振肿瘤退缩分级（mrTRG）评估治疗反应。根据mrTRG将患者分为反应者或无反应者。采用t检验和重复测量方差分析（ANOVA）评估γ-H2AX水平的动态变化，并采用多水平线性回归模型分析γ-H2AX水平与治疗反应之间的关系。
30例患者中有19例（63.33%）被分类为反应者。无反应者和反应者之间γ-H2AX水平存在显著动态变化（P=0.01）。多水平线性回归模型显示反应者的γ-H2AX水平有升高趋势[1.17，95%置信区间（CI）：-0.02至2.34，P=0.053]。从基线到治疗中期、治疗结束时以及CCRT后六周，γ-H2AX水平存在显著差异。与未达到病理完全缓解（pCR）的患者相比，CCRT后达到pCR的患者γ-H2AX比值显著更高（P=0.04）。然而，在多水平线性回归模型中未发现显著差异。
γ-H2AX可能有潜力作为接受术前CCRT的局部晚期直肠癌患者治疗反应的生物标志物，尽管还需要进一步验证。
