Expression of DTX2 molecule in colorectal cancer tissues and its clinical significances_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

MA Zhennan , XU Guangda , LIU Fuquan , ZHANG Xiaowei ,  ZHAO Xuefeng

Department of General Surgery, Dalian University Affiliated Xinhua Hospital, Dalian, Liaoning 116021, P. R. China;

Corresponding author：

ZHAO Xuefeng, Email: zoserbong@163.com

Keywords：

colorectal cancer; DTX2 molecule; prognosis; database data; clinical data

DOI：

10.7507/1007-9424.202010080

Video：

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Objective To detect expression of DTX2 molecule in colorectal cancer (CRC) tissues and investigate its clinical significances.Methods Oncomine and GEPIA databases were used to analyze the expression of DTX2 gene in CRC tissues and normal colorectal tissues, and online data of human protein atlas (HPA) was used to analyze the relationship between DTX2 protein expression and survival prognosis of patients with CRC. The expressions of DTX2 mRNA and protein were detected in the 55 cases of CRC tissues and corresponding paracancerous normal (PN) tissues by using qRT-PCR, Western blot, and immunohistochemistry methods, respectively. The correlations between the expression of DTX2 and the clinicopathologic characteristics were analyzed.Results ① The data from Oncomine and GEPIA databases showed that the expression levels of DTX2 mRNA in the CRC tissues were significantly higher than those in the normal colorectal tissues (P<0.05); HPA online data analysis showed that the overall survival of CRC patients with low expression of DTX2 was better than that with high expression of DTX2 (P=0.009 8). ② The results of qRT-PCR and Western blot showed that the expression levels of DTX2 mRNA and protein in the CRC tissues were higher than those in the PN tissues (t=0.722, P<0.001; t=1.314, P<0.001); The results of immunohistochemical staining showed that the positive rate of DTX2 protein expression in the CRC tissues was higher than that in the PN tissues (χ²=0.899, P<0.001). The positive rate of DTX2 protein expression and the expression levels of DTX2 mRNA and protein were related to the depth of tumor invasion, lymph node metastasis, and TNM stage of CRC patients, that was, the deeper depth of tumor invasion, the more lymph node metastasis, and the later TNM stage, the higher positive rate of DTX2 protein expression, the higher expression levels of DTX2 mRNA and protein (P<0.05).Conclusions DTX2 protein may be a novel biomarker for estimating progression of CRC. However, prognosis evaluation of DTX2 protein on CRC needs further clinical research.

Citation： MA Zhennan, XU Guangda, LIU Fuquan, ZHANG Xiaowei, ZHAO Xuefeng. Expression of DTX2 molecule in colorectal cancer tissues and its clinical significances. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2021, 28(7): 861-866. doi: 10.7507/1007-9424.202010080 Copy

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6.	Nakayama M, Oshima M. Mutant p53 in colon cancer. J Mol Cell Biol, 2019, 11(4): 267-276.
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13.	Gaedcke J, Grade M, Jung K, et al. Mutated KRAS results in overexpression of DUSP4, a MAP-kinase phosphatase, and SMYD3, a histone methyltransferase, in rectal carcinomas. Genes Chromosomes Cancer, 2010, 49(11): 1024-1034.
14.	王锡山. 中美结直肠癌流行病学特征及防诊治策略的对比分析. 中华结直肠疾病电子杂志, 2017, 6(6): 447-453.
15.	Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin, 2016, 66(2): 115-132.
16.	Xie B, Zhang P, Liu M, et al. Deltex1 polymorphisms are associated with hepatitis B vaccination non-response in Southwest China. PLoS One, 2016, 11(2): e0149199.
17.	Zhi X, Chen C. WWP1: a versatile ubiquitin E3 ligase in signaling and diseases. Cell Mol Life Sci, 2012, 69(9): 1425-1434.
18.	Luo D, de Morree A, Boutet S, et al. Deltex2 represses MyoD expression and inhibits myogenic differentiation by acting as a negative regulator of Jmjd1c. Proc Natl Acad Sci U S A, 2017, 114(15): E3071-E3080.
19.	Maki K, Sasaki K, Sugita F, et al. Acute myeloid leukemia with t(7; 21)(q11.2;q22) expresses a novel, reversed-sequence RUNX1-DTX2 chimera. Int J Hematol, 2012, 96(2): 268-273.
20.	Tsuchiya M, Nakajima Y, Hirata N, et al. Ubiquitin ligase CHIP suppresses cancer stem cell properties in a population of breast cancer cells. Biochem Biophys Res Commun, 2014, 452(4): 928-932.
21.	Chen J, Imanaka N, Chen J, et al. Hypoxia potentiates Notch signaling in breast cancer leading to decreased E-cadherin expression and increased cell migration and invasion. Br J Cancer, 2010, 102(2): 351-360.
22.	Götte M, Greve B, Kelsch R, et al. The adult stem cell marker Musashi-1 modulates endometrial carcinoma cell cycle progression and apoptosis via Notch-1 and p21WAF1/CIP1. Int J Cancer, 2011, 129(8): 2042-2049.

1. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.
2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin, 2019, 69(1): 7-34.
3. Chen W. Cancer statistics: updated cancer burden in China. Chin J Cancer Res, 2015, 27(1): 1.
4. Chen W, Sun K, Zheng R, et al. Cancer incidence and mortality in China, 2014. Chin J Cancer Res, 2018, 30(1): 1-12.
5. 孙可欣, 郑荣寿, 张思维, 等. 2015年中国分地区恶性肿瘤发病和死亡分析. 中国肿瘤, 2019, 28(1): 1-11.
6. Nakayama M, Oshima M. Mutant p53 in colon cancer. J Mol Cell Biol, 2019, 11(4): 267-276.
7. Wen J, Min X, Shen M, et al. ACLY facilitates colon cancer cell metastasis by CTNNB1. J Exp Clin Cancer Res, 2019, 38(1): 401.
8. 李向阳, 刘臻. 甲状腺乳头状癌中DTX2的表达与临床意义. 沈阳: 中国医科大学, 2018.
9. Thul PJ, Lindskog C. The human protein atlas: A spatial map of the human proteome. Protein Sci, 2018, 27(1): 233-244.
10. 赵雪峰, 赵美兰, 许广大. TMPRSS4在胃癌中的表达及其临床意义. 中国医科大学学报, 2018, 47(11): 969-974.
11. Ki DH, Jeung HC, Park CH, et al. Whole genome analysis for liver metastasis gene signatures in colorectal cancer. Int J Cancer, 2007, 121(9): 2005-2012.
12. Skrzypczak M, Goryca K, Rubel T, et al. Modeling oncogenic signaling in colon tumors by multidirectional analyses of microarray data directed for maximization of analytical reliability. PLoS One, 2010, 5(10): e13091.
13. Gaedcke J, Grade M, Jung K, et al. Mutated KRAS results in overexpression of DUSP4, a MAP-kinase phosphatase, and SMYD3, a histone methyltransferase, in rectal carcinomas. Genes Chromosomes Cancer, 2010, 49(11): 1024-1034.
14. 王锡山. 中美结直肠癌流行病学特征及防诊治策略的对比分析. 中华结直肠疾病电子杂志, 2017, 6(6): 447-453.
15. Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin, 2016, 66(2): 115-132.
16. Xie B, Zhang P, Liu M, et al. Deltex1 polymorphisms are associated with hepatitis B vaccination non-response in Southwest China. PLoS One, 2016, 11(2): e0149199.
17. Zhi X, Chen C. WWP1: a versatile ubiquitin E3 ligase in signaling and diseases. Cell Mol Life Sci, 2012, 69(9): 1425-1434.
18. Luo D, de Morree A, Boutet S, et al. Deltex2 represses MyoD expression and inhibits myogenic differentiation by acting as a negative regulator of Jmjd1c. Proc Natl Acad Sci U S A, 2017, 114(15): E3071-E3080.
19. Maki K, Sasaki K, Sugita F, et al. Acute myeloid leukemia with t(7; 21)(q11.2;q22) expresses a novel, reversed-sequence RUNX1-DTX2 chimera. Int J Hematol, 2012, 96(2): 268-273.
20. Tsuchiya M, Nakajima Y, Hirata N, et al. Ubiquitin ligase CHIP suppresses cancer stem cell properties in a population of breast cancer cells. Biochem Biophys Res Commun, 2014, 452(4): 928-932.
21. Chen J, Imanaka N, Chen J, et al. Hypoxia potentiates Notch signaling in breast cancer leading to decreased E-cadherin expression and increased cell migration and invasion. Br J Cancer, 2010, 102(2): 351-360.
22. Götte M, Greve B, Kelsch R, et al. The adult stem cell marker Musashi-1 modulates endometrial carcinoma cell cycle progression and apoptosis via Notch-1 and p21WAF1/CIP1. Int J Cancer, 2011, 129(8): 2042-2049.

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Expression of DTX2 molecule in colorectal cancer tissues and its clinical significances

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