肝腫瘤切除前後的氧化壓力及抗氧化能力之變化及與肝癌復發的相關性

肝癌患者由於癌症病程的進展會造成體內氧化壓力與抗氧化能力的失衡，但是肝癌患者接受腫瘤切除前後之氧化壓力與抗氧化能力的變化及與肝癌復發狀況的相關性則尚未清楚。本研究目的是比較肝癌復發與未復發患者於腫瘤切除前後的血漿、肝臟腫瘤組織與鄰近周邊正常組織的氧化壓力及抗氧化能力之變化；同時探討氧化壓力及抗氧化能力與肝癌復發的相關性。於臺中榮民總醫院一般外科招募共招募 83 位欲接受肝腫瘤切除患者。採集患者腫瘤切除前一天和腫瘤切除後一個月的空腹血液進行氧化壓力指標 (丙二醛)、總抗氧化能力、穀胱甘肽與相關抗氧化酵素活性分析，以及分析患者肝臟腫瘤組織及其鄰近周邊正常組織中丙二醛、總抗氧化能力與穀胱甘肽濃度。以病歷查詢患者於腫瘤切除日至 2019 年 1 月 28 日止的復發情形。結果顯示 39 位復發與 44 位未復發的肝癌患者於腫瘤切除後的氧化壓力皆較腫瘤切除前有顯著下降；穀胱甘肽、氧化型穀胱甘肽濃度及穀胱甘肽還原酶活性於腫瘤切除後顯著上升。肝癌復發患者相較於未復發患者在接受腫瘤切除前有顯著較高的血漿穀胱甘肽還原酶活性及顯著較低的血漿穀胱甘肽硫轉移酶活性。肝癌復發患者的腫瘤組織及鄰近周邊正常組織的穀胱甘肽濃度顯著高於未復發者。利用Cox比例風險模式分析結果顯示肝癌患者接受腫瘤切除前血漿穀胱甘肽還原酶 (HR, 0.964, 95% CI, 0.936 – 0.993) 與穀胱甘肽過氧化酶 (HR, 0.994, 95% CI, 0.989 – 1.000) 活性下降及鄰近周邊正常組織中總抗氧化能力數值 (HR, 0.993, 95% CI, 0.986 – 1.000) 下降會顯著增加肝癌復發風險。肝癌復發與未復發患者於腫瘤切除前後有相似的氧化壓力及抗氧化能力的變化，且肝癌患者接受腫瘤切除前的血漿穀胱甘肽還原酶與穀胱甘肽過氧化酶活性以及鄰近周邊正常組織中總抗氧化能力皆可預測肝癌患者接受腫瘤切除後之肝癌復發情形。

Patients might have an imbalance of oxidative stress and antioxidant capacities during the progression of hepatocellular carcinoma (HCC). However, it is not clear the changes of oxidative stress and antioxidant capacities before and after tumor resection and the association with the recurrence of HCC. The purpose of this study was to compare the changes of oxidative stress and antioxidant capacities in plasma before and after tumor resection, and in tumor and adjacent normal liver tissue in patients with recurrent and non-recurrent HCC. Additional purpose was to evaluate the association of oxidative stress and antioxidant capacities with the recurrence of HCC. We recruited 83 patients with HCC who would undergo tumor resection from the division of general surgery of Taichung Veterans General Hospital, Taiwan. Fasting blood samples were collected on the day before and one month after tumor resection to measure oxidative stress marker (malondialdehyde, MDA), trolox equivalent antioxidant capacity (TEAC), glutathione and antioxidant enzymes. Tumor and adjacent normal liver tissue were collected to measure MDA, TEAC and glutathione. The duration of the recurrence was recorded from the day receiving tumor resection to January 28, 2019. Results showed 39 patients with recurrent HCC and 44 patients with non-recurrent HCC had significantly lower levels of MDA, but had significantly higher levels of glutathione and oxidized glutathione and the activity of glutathione reductase (GRd) after tumor resection compared to the levels before tumor resection. Patients with recurrent HCC had significantly higher activity of GRd, but had significantly lower activity of glutathione-S-transferase (GST) compared to patients with non-recurrent HCC. There was a significantly higher glutathione level in both tumor and adjacent normal liver tissues of patients with recurrent HCC compared to patients with non-recurrent HCC. Cox proportional hazard analysis showed the decreased of plasma GR (HR, 0.964, 95% CI, 0.936 – 0.993) and glutathione peroxidase (GPx) (HR, 0.994, 95% CI, 0.989 – 1.000) activities before tumor resection and the decreased of TEAC level (HR, 0.993, 95% CI, 0.986 – 1.000) in adjacent normal liver tissue were significantly associated with the increased risk of HCC recurrence. In conclusion, there were similar changes of oxidative stress and antioxidant capacities before and after tumor resection in patients with recurrent and non-recurrent HCC. In addition, plasma GRd and GPx activities before tumor resection and TEAC in adjacent normal tissue were significant predictors of HCC recurrence.