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中华结直肠疾病电子杂志

中华结直肠疾病电子杂志 ›› 2019, Vol. 08 ›› Issue (06) : 560 -565. doi: 10.3877/cma.j.issn.2095-3224.2019.06.004

所属专题： 文献；

论著

ETS2在结直肠癌组织中的表达及临床意义
汪军1, 黄裕2, 孙强2, 魏舒迅2, 祝徐军1, 王长明1, 李新星2,†(), 徐健1,†()   
  1. 1. 201999　上海市宝山区中西医结合医院普外科
    2. 200003　上海长征医院结直肠外科
  • 收稿日期:2019-03-25 出版日期:2019-12-25
  • 通信作者: 李新星, 徐健
  • 基金资助:
    国家自然科学基金项目(No.81402002)

Expressions of ETS2 in colorectal cancer tissues and its clinical significance

Jun Wang1, Yu Huang2, Qiang Sun2, Shuxun Wei2, Xujun Zhu1, Changming Wang1, Xinxing Li2,†(), Jian Xu1,†()   

  1. 1. Department of General Surgery, Baoshan Integrated Traditional Chinese and Western Medicine Hospital, Shanghai 201999, China
    2. Department of Colorectal Surgery, Shanghai Changzheng Hospital, Shanghai 200003, China
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引用本文：

汪军, 黄裕, 孙强, 魏舒迅, 祝徐军, 王长明, 李新星, 徐健. ETS2在结直肠癌组织中的表达及临床意义[J]. 中华结直肠疾病电子杂志, 2019, 08(06): 560-565.

Jun Wang, Yu Huang, Qiang Sun, Shuxun Wei, Xujun Zhu, Changming Wang, Xinxing Li, Jian Xu. Expressions of ETS2 in colorectal cancer tissues and its clinical significance[J]. Chinese Journal of Colorectal Diseases(Electronic Edition), 2019, 08(06): 560-565.

目的

探讨转录因子ETS2（E-twenty six 2）在结直肠癌组织中的表达情况，分析其与结直肠癌患者临床病理参数之间的关系，并评估其临床预后价值。

方法

收集新鲜的结直肠癌、癌旁和相应正常组织，以及结直肠癌和癌旁组织的石蜡标本，采用实时荧光定量PCR法检测组织中ETS2 mRNA的表达，免疫组化检测石蜡切片中ETS2蛋白的表达。

结果

结直肠癌组织中ETS2 mRNA的表达明显高于癌旁组织和正常组织（P<0.001），而癌旁组织和正常组织中的ETS2 mRNA表达量差异无统计学意义（P>0.05）。免疫组化结果显示ETS2在52.07%（63/121）的结直肠癌中表达，而仅在13.04%（6/46）的癌旁组织中表达，两者比较差异有统计学意义（P<0.05）。ETS2表达与肿瘤分化程度、浸润深度、淋巴结转移以及MMR状态有关（P<0.05）。ETS2表达与结直肠癌患者术后无进展生存有关（P<0.001）。采用COX多因素回归分析发现，ETS2表达（HR：0.461，95%CI：0.271~0.683，P=0.003）和浸润深度（HR：0.352，95%CI：0.113~0.769，P=0.015）是结直肠癌患者术后无进展生存的独立预后因子。

结论

与癌旁组织相比，ETS2在结直肠癌组织中的转录和翻译水平都过表达，ETS2是预测结直肠癌患者术后无进展生存的潜在标记物。

关键词: 结直肠肿瘤, 预后, ETS2, 浸润深度, 标记物
Objective

To investigate the expressions of ETS2 (E-twenty six 2) in colorectal cancer tissues, analyze the relationships between clinic-pathological parameters and ETS2 expression, and evaluate its clinical prognostic value.

Methods

We collected fresh colorectal cancer, paracancerous and the corresponding normal tissues, and specimens of paraffin of colorectal cancer and adjacent to carcinoma. Real-time fluorescent quantitative PCR and immunohistochemistry were used to detect ETS2 mRNA expression and protein expression respectively.

Results

Our results showed that the expression of ETS2 mRNA in colorectal cancer tissues was significantly higher than that in adjacent and normal tissues (P<0.001), while there was no significant difference between adjacent and normal tissues (P>0.05). Immuno-histochemical results showed that ETS2 was expressed in 52.07% (63/121) colorectal cancer tissues, but only in 13.04% (6/46) para-cancerous tissues, showing a significant difference (P<0.05). ETS2 expression was closely associated with tumor differentiation, invasion depth, lymph node metastasis, and MMR status (all P<0.05). ETS2 expression was associated with postoperative progression-free survival in patients with colorectal cancer (P<0.001). Multivariate regression analysis using Cox model showed that ETS2 expression (HR: 0.461, 95% CI: 0.271~0.683, P=0.003) and infiltration depth (HR: 0.352, 95% CI: 0.113~0.769, P=0.015) were independent prognostic factors for postoperative progressive-free survival of colorectal cancer patients.

Conclusion

Compared with para-cancerous tissues, ETS2 was overexpressed in transcriptional and translational levels of colorectal cancer. Moreover, ETS2 was a potential marker for predicting postoperative progression-free survival in patients.

Key words: Colorectal neoplasms, Prognosis, ETS2, Infiltration depth, Marker
图1 ETS2 mRNA的表达。1A：结直肠癌、癌旁和正常配对的新鲜组织。1B：病理分期Ⅰ期和Ⅱ~Ⅲ期结直肠癌新鲜组织
图2 ETS2蛋白在结直肠癌、癌旁组织中的表达情况，其中蓝色颗粒代表细胞核、不表达ETS2蛋白，褐色颗粒代表细胞核表达ETS2蛋白。2A：ETS2蛋白在癌旁组织和癌组织中的表达（×100倍）；2B：ETS2蛋白在癌组织中低表达和高表达图（×200倍）
图3 Kaplan-Meier生存曲线。ETS2高表达的结直肠癌患者无病生存期更差
表1 ETS2蛋白的表达与结直肠癌患者病理临床参数的关系
参数 例数 ETS2表达 检验值 P值
低表达 高表达
性别 ? ? ? 0.007 0.935
? 　女 34 17 17 ? ?
? 　男 87 41 46 ? ?
年龄（岁） ? ? ? 0.012 0.911
? 　≤60 38 19 19 ? ?
? 　>60 83 39 44 ? ?
肿瘤直径（cm） ? ? ? 1.943 0.163
? 　≤3 99 44 55 ? ?
? 　>3 22 14 8 ? ?
肿瘤位置 ? ? ? 0.871 0.351
? 　结肠 73 38 35 ? ?
? 　直肠 48 20 28 ? ?
分化程度 ? ? ? 19.577 <0.001
? 　中/高分化 38 30 8 ? ?
? 　低/未分化 83 28 55 ? ?
浸润深度 ? ? ? 22.036 <0.001
? 　T1 44 34 10 ? ?
? 　T2-T4 77 24 53 ? ?
淋巴结转移 ? ? ? 9.593 0.002
? 　N0 69 42 27 ? ?
? 　N1-N2 52 16 36 ? ?
MMR状态 ? ? ? 4.811 0.028
? 　MSS 80 42 38 ? ?
? 　MSI 41 16 35 ? ?
进展* ? ? ? 7.042 0.008
? 　有 55 25 30 ? ?
? 　无 34 26 8 ? ?
表2 结直肠癌临床病理参数的单因素和多因素的无进展生存分析
预后因素 单因素分析 多因素分析
RR 95%CI P值 RR 95%CI P值#
性别 1.013 0.678~1.644 0.732 ? ? ?
年龄（岁） 1.018 0.772~1.809 0.453 ? ? ?
肿瘤直径（cm） 0.943 0.525~1.372 0.563 ? ? ?
肿瘤位置 1.291 0.821~2.692 0.702 ? ? ?
分化程度 0.094 0.175~0.457 0.001 0.816 0.124~2.706 0.114
浸润深度 0.303 0.156~0.489 0.002 0.352 0.113~0.769 0.015
淋巴结转移是否 0.413 0.263~0.509 0.011 0.795 0.271~2.281 0.670
病理分期 0.203 0.052~0.317 0.001 0.422 0.313~0.569 0.005
MMR状态 0.403 0.356~0.889 0.037 0.852 0.683~1.678 0.502
ETS2表达 0.251 0.161~0.411 0.000 0.461 0.271~0.683 0.003
[1]
Han S, Gao J, Zhou Q, et al. Role of intestinal flora in colorectal cancer from the metabolite perspective: a systematic review [J]. Cancer Management and Research, 2018, 10: 199-206.
[2]
de Klerk CM, Gupta S, Dekker E, et al. Expert Working Group ′Coalition to reduce inequities in colorectal cancer screening′ of the World Endoscopy O. Socioeconomic and ethnic inequities within organised colorectal cancer screening programmes worldwide [J]. Gut, 2018, 67(4): 679-687.
[3]
Kayser K, Acquati C, Reese JB, et al. A systematic review of dyadic studies examining relationship quality in couples facing colorectal cancer together [J]. Psycho-oncology, 2018, 27(1): 13-21.
[4]
Fry EA, Inoue K. Aberrant expression of ETS1 and ETS2 proteins in cancer [J].Cancer reports and reviews, 2018, 2(3): 10.
[5]
Zhang G, Zhang L, Yang X, et al. High ETS2 expression predicts poor prognosis in acute myeloid leukemia patients undergoing allogeneic hematopoietic stem cell transplantation [J]. Annals of hematology, 2019, 98(2): 519-525.
[6]
Wallace JA, Li F, Balakrishnan S, et al. Ets2 in tumor fibroblasts promotes angiogenesis in breast cancer [J]. PloS One, 2013, 8(8): e71533.
[7]
Torres A, Alshalalfa M, Davicioni E, et al. ETS2 is a prostate basal cell marker and is highly expressed in prostate cancers aberrantly expressing p63 [J]. The Prostate, 2018, 78(12): 896-904.
[8]
Fry EA, Mallakin A, Inoue K. Translocations involving ETS family proteins in human cancer [J]. Integrative cancer science and therapeutics, 2018, 5(4): 4-12.
[9]
Zhang GW, Tian X, Li Y, et al. Down-regulation of ETS2 inhibits the invasion and metastasis of renal cell carcinoma cells by inducing EMT via the PI3K/Akt signaling pathway [J]. Biomedicine & pharmacotherapy, 2018, 104: 119-126.
[10]
Liu DD, Kang Y. Ets2 anchors the prometastatic function of mutant p53 in osteosarcoma [J]. Genes & development, 2017, 31(18): 1823-1824.
[11]
Peraki I, Palis J, Mavrothalassitis G. The Ets2 Repressor Factor (Erf) Is Required for Effective Primitive and Definitive Hematopoiesis [J]. Molecular and cellular biology, 2017, 37(19): e00183-17.
[12]
Ma S, Fang Z, Luo W, et al. The C-ETS2-TFEB axis promotes neuron survival under oxidative stress by regulating lysosome activity [J]. Oxidative medicine and Cellular Longevity, 2016, 2016: 4693703.
[13]
Liu X, Zhang C, Zhang Z, et al. E26 transformation-specific transcription factor ETS2 as an oncogene promotes the progression of hypopharyngeal cancer [J]. Cancer biotherapy & radiopharmaceuticals, 2017, 32(9): 327-334.
[14]
Baker K, Foulkes WD, Jass JR. MSI-H colorectal cancers preferentially retain and expand intraepithelial lymphocytes rather than peripherally derived CD8+ T cells[J]. Cancer Immunology, Immunotherapy: CII, 2009, 58(1): 135-144.
[15]
Lawes DA, Pearson T, Sengupta S, et al. Is MSI-H of value in predicting the development of metachronous colorectal cancer? [J]. European Journal of Cancer, 2006, 42(4): 473-476.
[16]
Lee JJ, Chu E. Recent advances in the clinical development of immune checkpoint blockade therapy for mismatch repair proficient (pMMR)/non-MSI-H metastatic colorectal cancer [J]. Clinical Colorectal Cancer, 2018, 17(4): 258-273.
[17]
Gatalica Z, Vranic S, Xiu J, et al. High microsatellite instability (MSI-H) colorectal carcinoma: a brief review of predictive biomarkers in the era of personalized medicine [J]. Familial cancer, 2016, 15(3): 405-412.
[18]
Sclafani F. PD-1 inhibition in metastatic dMMR/MSI-H colorectal cancer [J]. The Lancet Oncology, 2017, 18(9): 1141-1142.
[19]
Diaz LA. The promise of liquid biopsy in colorectal cancer [J]. Clinical Advances in Hematology & Oncology: H&O, 2014, 12(10): 688-689.
[20]
Ray K. Colorectal cancer: Liquid biopsy enables real-time monitoring of molecular alterations in CRC [J]. Nature reviews Gastroenterology & hepatology, 2015, 12(7): 372.
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