大腸直腸癌患者腫瘤切除前後的半胱胺酸狀態與氧化壓力及穀胱甘肽相關抗氧化能力之關係

大腸直腸癌患者相較健康受試者有較高的氧化壓力及抗氧化能力。半胱胺酸除了可透過自身結構的硫氫基 (-SH)捕捉自由基外，也是穀胱甘肽生合成的速限物質。若半胱胺酸處在缺乏的狀況可能會影響自身的抗氧化能力及限制穀胱甘肽的生合成，進而干擾大腸直腸癌患者的氧化壓力及抗氧化能力的平衡。目前尚未清楚大腸直腸癌患者於腫瘤切除前後的血漿及組織半胱胺酸狀態是否會影響血漿及組織的氧化壓力。本研究目的為探討大腸直腸癌患者於腫瘤切除前後以及大腸直腸腫瘤和鄰近周邊正常組織的半胱胺酸與氧化壓力以及穀胱甘肽相關抗氧化能力的變化及相關性。 於臺中榮民總醫院大腸直腸外科招募欲接受大腸直腸腫瘤切除的患者。採集患者於腫瘤切除前和切除後一個月的空腹血液，以及收集大腸直腸癌腫瘤組織和鄰近周邊正常組織，用以分析半胱胺酸、同半胱胺酸、氧化壓力指標 (丙二醛、高級氧化蛋白產物)、抗氧化能力指標 (總抗氧化能力、穀胱甘肽、氧化型穀胱甘肽、穀胱甘肽相關酵素活性、超氧歧化酶活性)。 結果顯示大腸直腸癌患者腫瘤切除後的血漿半胱胺酸、同半胱胺酸、高級氧化蛋白產物以及穀胱甘肽相關抗氧化能力的數值皆顯著高於腫瘤切除前。腫瘤組織的半胱胺酸、同半胱胺酸、高級氧化蛋白產物、穀胱甘肽及其相關抗氧化酵素的數值顯著高於鄰近周邊正常組織，但丙二醛的數值則是鄰近周邊正常組織顯著高於腫瘤組織。調整相關干擾因子後，腫瘤切除前的血漿半胱胺酸濃度與血漿同半胱胺酸、總抗氧化能力及穀胱甘肽硫轉移酶的數值呈顯著正相關。腫瘤切除後的血漿半胱胺酸則與血漿同半胱胺酸、穀胱甘肽及氧化型穀胱甘肽的濃度呈顯著正相關。鄰近周邊正常組織的半胱胺酸濃度與同半胱胺酸、氧化壓力指標以及抗氧化能力指標的數值大多呈顯著正相關。然而，腫瘤組織的半胱胺酸濃度與丙二醛及高級氧化蛋白產物無顯著相關性，僅與總抗氧化能力及抗氧化酵素活性有顯著相關性。 大腸直腸癌患者雖在腫瘤切除後一個月相較腫瘤切除前以及腫瘤組織相較鄰近周邊正常組織有較高的氧化壓力，不過同時也因有較高的血漿半胱胺酸濃度及穀胱甘肽相關抗氧化能力能與之抗衡。

Patients with colorectal cancer has been shown to have increased oxidative stress and decreased antioxidant capacities when compared to healthy controls. Cysteine not only would directly scavenge free radicals though its thiol group (-SH), but also be a limiting substrate for glutathione (GSH) synthesis. If cysteine is in a deficient state, it might affect its antioxidant ability, and limit GSH synthesis, and may further interfere with the balance of oxidative stress and antioxidant capacity in colorectal cancer patients. However, it is not clear whether cysteine status in plasma and tissue has an impact on plasma and tissue oxidative stress and GSH related antioxidant capacities in colorectal cancer patients before and after tumor resection. The purpose of this study was to evaluate the changes and associations of cysteine with oxidative stress and GSH-related antioxidant capacity in plasma and tissue before and after tumor resection in patients with colorectal cancer. We recruited patients with colorectal cancer and were scheduled to undergo tumor resection from the Colorectal Surgery Division of Taichung Veterans General Hospital, Taichung. Fasting blood samples were drawn on one day before tumor resection (pre-resection) and 1 month after tumor resection (post-resection). Colorectal tumor tissue and its adjacent normal tissues were obtained at the time of surgical resection. Samples were used to measure cysteine, homocysteine, and oxidative stress indicators (malondialdehyde, MDA; advanced oxidized protein products, AOPPs), antioxidant capacity indicators (trolox equivalent antioxidant capacity, TEAC; GSH; oxidized glutathione, GSSG; GSH-dependent enzymes activities, superoxide dismutase activity, SOD). Results showed that patients had significantly higher levels of plasma cysteine, homocysteine, AOPPs and GSH-dependent antioxidant capacity after tumor resection when compared with values of pre-resection. Levels of cysteine, homocysteine, AOPPs, GSH, and activities of GSH-related antioxidant enzymes in tumor tissue were significantly higher than those levels in adjacent normal tissues, while MDA level in adjacent normal tissue was higher than the level in tumor tissue. After adjusting for confounders, plasma cysteine concentration was significantly positively associated with the levels of plasma homocysteine, TEAC and glutathione S-transferase (GST) at pre-resection. Plasma cysteine concentration was significantly positively associated with homocysteine, GSH and GSSG at post-resection. Cysteine concentration in adjacent normal tissue was significantly positively associated with levels of homocysteine, oxidative stress and most of antioxidant capacity indicators in adjacent normal tissue, while cysteine levels in tumor tissue was significantly associated with levels of homocysteine, TEAC, and antioxidant enzyme activities in tumor tissue.Although patients with colorectal cancer had higher oxidative stress status in plasma after tumor resection and in tumor tissue when compared with status in plasma at post-resection and adjacent normal tissue, they were simultaneously had higher cysteine and GSH-related antioxidant capacity to cope with high oxidative stress status.