Evaluation of Carcinoembryonic Antigen, Vascular Endothelial Growth Factor, Neutrophil Elastase as Serological Biomarkers in Patients with Colorectal Cancer

驗證癌胚胎抗原，血管內皮生長因子，嗜中性白血球彈性蛋白酶作為大腸癌病人的血清生物標記

林華卿(Hua-Ching Lin) ； 程俊嘉(Chun-Chia Cheng) ； 黃啟栓(Chi-Shuan Huang) ； 黃任嫻(Jen-Hsien Huang) ； 何愛生(Ai-Sheng Ho)

《中華民國大腸直腸外科醫學會雜誌》 33卷2期 (2022/06) Pp. 51-59

https://doi.org/10.6312/SCRSTW.202206_33(2).11026

摘要

Background. Tumor microenvironment contains tumor cells and other non-tumor cells such as inflammatory cytokines and immune cells. With the high proliferation of tumor cells, VEGF is secreted by tumor cells for exacerbating angiogenesis. Immune cells such as neutrophils recruit to inflammatory tumor tissues and secrete neutrophil elastase (NE) to enhance tumor proliferation and angiogenesis. Aims. We intended to evaluate conventional CEA and high abundant VEGF and NE as the serological biomarkers in patients with colorectal cancer (CRC). Methods. Cancer tissues (n = 3) were confirmed by methylene blue stain. Neutrophils were detected in the CRC tissues by naphthol AS-D chloroacetate esterase stain and MALDI-TOF MS targeting HNP-1 (m/z 3442). In addition, CEA, VEGF, and NE were measured by ELISA in the sera of CRC patients. The correlation statistical analysis and ROC curve were used to evaluate CEA, VEGF, and NE as the serological biomarkers in the CRC patients (n = 27 vs. n = 14 from the healthy volunteers). Results.We found that neutrophils highly accumulated in the CRC tissues compared to the adjacent normal tissues. Meanwhile, CEA, VEGF, and NE all increased in the sera of CRC patients compared to the healthy volunteers, which are independently expressed. Area under ROC curve of CEA, VEGF, and NE was 0.76 (p = 0.008), 0.57 (p = 0.39), 0.76 (p = 0.0077), respectively, indicating that CEA and NE were reliable as the biomarker of CRC patients. Conclusions. We demonstrated that immune cell neutrophils accumulated in the CRC tissues and its secreted enzyme NE may be a serological biomarker of CRC. The study warrants further investigation for the functions of neutrophils in the CRC tumor microenvironment.

關鍵字

Colorectal cancer ； Biomarker ； Carcinoembryonic antigen (CEA) ； Vascular endothelial growth factor (VEGF) ； Neutrophil elastase (NE)

並列摘要

背景：腫瘤微環境包含腫瘤細胞和其他非腫瘤細胞例如發炎因子和免疫細胞。隨著腫瘤細胞的高度增殖，腫瘤細胞分泌VEGF加劇血管生成。嗜中性白血球細胞等免疫細胞遷移到發炎腫瘤組織並分泌neutrophil elastase（NE）以增強腫瘤增殖和血管生成。目的：評估常規CEA，VEGF，NE作為大腸直腸癌（CRC）患者的血清生物標誌。方法：臨床大腸癌症組織（n = 3）通過亞甲藍（methylene blue）染色確認。在CRC組織中通過萘酚AS-D氯乙酸酯酶（naphthol AS-D chloroacetate esterase）染色和MALDI-TOF MS靶向分析HNP-1（m/z 3442）檢測嗜中性白血球。此外，通過ELISA測量CRC患者血清中的CEA、VEGF和NE。相關統計分析和ROC曲線用於評估CEA、VEGF、NE作為CRC患者的血清學生物標誌物（n = 27 vs. n = 14來自健康志願者）。結果：我們發現大腸癌組織有大量嗜中性白血球聚集，相對於健康受試者，病人血清中大量表現CEA、VEGF、NE，但彼此之間並不具有相關性。CEA、VEGF、NE的ROC曲線面積分別為0.76（p = 0.008），0.57（p = 0.39），0.76（p = 0.0077），顯示CEA及NE可能為大腸癌生物標誌。結論：我們證明在大腸直腸癌組織中積累嗜中性白血球細胞，其分泌的NE可能是大腸直腸癌的血清學生物標誌。該研究值得進一步研究嗜中性白血球在CRC腫瘤微環境中的功能。

並列關鍵字

結直腸癌 ； 生物標誌物 ； 癌胚抗原（CEA） ； 血管內皮生長因子（VEGF） ； 中性粒細胞彈性蛋白酶（NE）

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