Expressions and clinical significances of Runx3 and CHD5 in colorectal cancer

doi:10.3760/cma.j.issn.1673-422X.2016.05.008

Abstract

Abstract: ObjectiveTo investigate the expressions and clinical significances of Runtdomainrelated 3 (Runx3) and chromodomain helicase DNAbinding protein 5 (CHD5) in colorectal cancer. MethodsNinetysix colorectal cancer tissue samples and matched adjacent normal tissues and 72 colorectal adenoma tissues were collected. Realtime quantitative polymerase chain reaction (qRTPCR) and Western blotting were used to detect the mRNA and protein expression of Runx3 and CHD5. The associations of Runx3 and CHD5 expression with clinical pathological characteristics, diagnostic value and prognosis relationship of patients were further analyzed. ResultsRunx3 and CHD5 relative expressions of mRNA and protein were 0.35±0.00, 0.28±0.02 and 0.26±0.02, 0.31±0.01, which were significantly lower than those in the matched adjacent tissues 0.95±0.02, 0.92±0.02 and 0.89±0.03, 0.93±0.02 (t=2.36, P＜0.05; t=1.25, P＜0.05; t=1.37, P＜0.05; t=1.13, P＜0.05) and colorectal adenoma tissues 0.89±0.02, 0.90±0.02 and 0.85±0.02, 0.87±0.04 (t=2.27, P＜0.05; t=2.16, P＜0.05; t=1.25, P＜0.05; t=2.65, P＜0.05). Runx3 and CHD5 expressions differed significantly between tumors with different TNM stages (χ2=4.65, P=0.031; χ2=7.89, P=0.005), depths of tumor invasion (χ2=4.17, P=0.041; χ2=4.86, P=0.028), lymph node statuses (χ2=4.20, P=0.040; χ2=7.02, P=0.008), or histological differentiation (χ2=7.31, P=0.036; χ2=9.54, P=0.023). Linear correlation analysis showed that the expressions of the two genes were positively correlated (r=0.572, P=0.001). Receiver operating characteristic (ROC) curve showed that Runx3 and CHD5 had diagnostic value (AUC were 0.712, 0.745; sensitivity and specificity were 45.9%, 52.5% and 83.6%, 81.4% respectively). Runx3 and CHD5 both low expression group compared with the other patient groups in overall survival time (χ2=8.156， P＜0.05) and progressionfree survival (χ2=6.325, P<0.05) had statistically significant differences. ConclusionRunx3 and CHD5 are low expressed in colorectal cancer and may prove useful as biomarkers for diagnosis target and prognostic indication in patients with colorectal cancer.

Key words: Colorectal neoplasms, Pathology, clinical, ROC curve, Runx3, CHD5

Ma Dong, Sun Xuejun. Expressions and clinical significances of Runx3 and CHD5 in colorectal cancer[J]. Journal of International Oncology, 2016, 43(5): 350-355.

References

［1］ Siegel R, Ma JM, Zou ZH, et al. Cancer statistics, 2014［J］. CA Cancer J Clin, 2014, 64(1): 9-29. DOI: 10.3322/caac.21208. ［2］ Wakeman C, Keenan J, Eteuati J, et al. Chemoprevention of colorectal neoplasia［J］. ANZ J Surg, 2015, In press. DOI: 10.1111/ans.13392. ［3］ Xue LN, Bai FH, Wang XY, et al. Expression of RUNX3 gene in pancreatic adenocarcinoma and its clinical significance［J］. Genet Mol Res, 2014, 13(2): 3940-3946. DOI: 10.4238/2014.May.23.4. ［4］ Fatemi M, Paul TA, Brodeur GM, et al. Epigenetic silencing of CHD5, a novel tumorsuppressor gene, occurs in early colorectal cancer stages［J］. Cancer, 2014, 120(2): 172-180. DOI: 10.1002/cncr.28316. ［5］ Yan W, Guo M. Epigenetics of colorectal cancer［J］. Methods Mol Biol, 2015, 1238: 405-424. DOI: 10.1007/9781493918041_22. ［6］ Williamson JS, Harris DA, Beynon J, et al. Review of the development of DNA methylation as a marker of response to neoadjuvant therapy and outcomes in rectal cancer［J］. Clin Epigenetics, 2015, 7(1): 70. DOI: 10.1186/s1314801501113. ［7］ Lotem J, Levanon D, Negreanu V, et al. Runx3 at the interface of immunity, inflammation and cancer［J］. Biochim Biophys Acta, 2015, 1855(2): 131-143. DOI: 10.1016/j.bbcan.2015.01.004. ［8］ Egan CM, Nyman U, Skotte J, et al. CHD5 is required for neurogenesis and has a dual role in facilitating gene expression and polycomb gene repression［J］. Dev Cell, 2013, 26(3): 223-236. DOI: 10.1016/j.devcel.2013.07.008. ［9］ Wong RR, Chan LK, Tsang TP, et al. CHD5 downregulation associated with poor prognosis in epithelial ovarian cancer［J］. Gynecol Obstet Invest, 2011, 72(3): 203-207. DOI: 10.1159/000323883. ［10］ Worthley DL, Whitehall VL, Le Leu RK, et al. DNA methylation in the rectal mucosa is associated with crypt proliferation and fecal shortchain fatty acids［J］. Dig Dis Sci, 2011, 56(2): 387-396. DOI: 10.1007/s1062001013124. ［11］ Mu WP, Wang J, Niu Q, et al. Clinical significance and association of RUNX3 hypermethylation frequency with colorectal cancer: a metaanalysis［J］. Onco Targets Ther, 2014, 7: 1237-1245. DOI: 10.2147/OTT.S62103. ［12］ Watanabe T, Kobunai T, Ikeuchi H, et al. RUNX3 copy number predicts the development of UCassociated colorectal cancer［J］. Int J Oncol, 2011, 38(1): 201-207. ［13］ Liu JB, Zhou QB, Xu JZ, et al. Influence of colorectal cancer tumor suppressor gene CHD5 methylation on its clinical and pathological characteristics［J］. J Biol Regul Homeost Agents, 2016, 29(4): 889-893. ［14］ Kim JH, Cho NY, Bae JM, et al. Nuclear maspin expression correlates with the CpG island methylator phenotype and tumor aggressiveness in colorectal cancer［J］. Int J Clin Exp Pathol, 2015, 8(2): 1920-1928. ［15］ Li X, Hu F, Wang Y, et al. CpG island methylator phenotype and prognosis of colorectal cancer in Northeast China［J］. Biomed Res Int, 2014: 236361. DOI: 10.1155/2014/236361. ［16］ Wang L, He S, Tu Y, et al. Downregulation of chromatin remodeling factor CHD5 is associated with a poor prognosis in human glioma［J］. J Clin Neurosci, 2013, 20(7): 958963. DOI: 10.1016/j.jocn.2012.07.021.

[1]	Zhang Rui, Chu Yanliu. Research progress of colorectal cancer risk assessment models based on FIT and gut microbiota [J]. Journal of International Oncology, 2024, 51(6): 370-375.
[2]	Gao Fan, Wang Ping, Du Chao, Chu Yanliu. Research progress on intestinal flora and non-surgical treatment of the colorectal cancer [J]. Journal of International Oncology, 2024, 51(6): 376-381.
[3]	Wang Junyi, Hong Kaibin, Ji Rongjia, Chen Dachao. Effect of cancer nodules on liver metastases after radical resection of colorectal cancer [J]. Journal of International Oncology, 2024, 51(5): 280-285.
[4]	Sun Guobao, Yang Qian, Zhuang Qingchun, Gao Binbin, Sun Xiaogang, Song Wei, Sha Dan. Research progress on the histopathological growth patterns of colorectal liver metastasis [J]. Journal of International Oncology, 2024, 51(2): 114-118.
[5]	Liu Debao, Sun Ziwen, Lu Shoutang, Xu Haidong. Expression and clinical significance of ASB6 in colorectal cancer tissues [J]. Journal of International Oncology, 2023, 50(8): 470-474.
[6]	Chen Zhuo, Tao Jun, Chen Lin, Ke Jing. Value of detection of peripheral blood miR-194 combined with fecal miR-143 in the clinical screening of colorectal cancer [J]. Journal of International Oncology, 2023, 50(5): 268-273.
[7]	Huang Zhen, Zhang Caiyutian, Ke Shaobo, Shi Wei, Zhao Wensi, Chen Yongshun. Construction of postoperative prognosis model for patients with colorectal cancer [J]. Journal of International Oncology, 2023, 50(3): 157-163.
[8]	Xu Liangfu, Li Yuanfei. Research progress on tumor microenvironment and immune combination therapy of MSS colorectal cancer [J]. Journal of International Oncology, 2023, 50(3): 186-190.
[9]	Liu Yujie, Zhao Zhiqiang, Wang Zicheng. Levels and diagnostic value of TOP2A and ERBB2 in peripheral blood mononuclear cells of patients with early colorectal cancer [J]. Journal of International Oncology, 2023, 50(12): 717-722.
[10]	Tao Hong, Yin Hong, Luo Hong, Tao Jiayu. Potential strategies for targeting tumor-associated macrophages to enhance the efficacy of immune checkpoint inhibitors for colorectal cancer [J]. Journal of International Oncology, 2023, 50(11): 683-687.
[11]	Wang Xi, Wu Chuanqing. Research progress in reversing multidrug resistance in colorectal cancer [J]. Journal of International Oncology, 2023, 50(1): 42-46.
[12]	Gao Yizhao, Liu Yang, Liu Qiulong, Xing Jinliang. Application of circulating cell-free nucleic acid in clinical diagnosis and treatment of colorectal cancer [J]. Journal of International Oncology, 2022, 49(9): 555-559.
[13]	He Zhefeng, Wu Yiyang, Li Zhenjun, Ying Xiaojiang. Predictive value of inflammatory markers in colorectal cancer [J]. Journal of International Oncology, 2022, 49(9): 560-563.
[14]	Zhao Ying, Zhang Gehong. Study on the correlations between AGR, PLR and NLR changes and chemotherapy efficacy of metastatic colorectal cancer [J]. Journal of International Oncology, 2022, 49(8): 473-477.
[15]	Huang Mengpan, Wang Xuehong, Lu Yongfu. Mechanism of FOXA2 in colorectal cancer and its application in diagnosis and treatment [J]. Journal of International Oncology, 2022, 49(8): 490-493.