The expression level of serum miR-96 and miR-424-5p in patients with colorectal cancer and its clinical significance
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摘要:
目的 分析血清miR-96和miR-424-5p表达与结直肠癌患者临床病理特征及预后的关系,探究两者联合检测对结直肠癌的诊断价值。 方法 收集2015年1—12月河南省人民医院收治的120例结直肠癌患者、40例结直肠腺瘤患者及40例健康受试者血清,采用实时荧光定量PCR(RT-PCR)方法检测血清miR-96和miR-424-5p的表达水平,分析其与结直肠癌患者临床病理特征及预后的关系,构建受试者工作特征(ROC)曲线评估血清miR-96和miR-424-5p的诊断效能。 结果 MiR-96和miR-424-5p在结直肠癌患者血清中的表达水平显著高于结直肠腺瘤患者和健康受试者,差异有统计学意义(均P < 0.05);TNM分期Ⅲ/Ⅳ期、低分化和有远处转移患者血清miR-96表达水平显著高于TNM分期Ⅰ/Ⅱ期、高中分化和无远处转移患者(均P < 0.01);TNM分期Ⅲ/Ⅳ期患者血清miR-424-5p表达水平显著高于TNM分期Ⅰ/Ⅱ期患者(均P < 0.01)。血清miR-96和miR-424-5p高表达患者的5年生存率及平均生存时间均低于血清miR-96和miR-424-5p低表达患者(均P < 0.01)。MiR-96和miR-424-5p诊断结直肠癌的曲线下面积(AUC)分别为0.727和0.720,特异性分别为71.2%和86.2%,两者联合检测的AUC和特异性分别为0.780和93.7%,均大于两者单独诊断(均P < 0.05)。 结论 血清miR-96和miR-424-5p表达水平升高与结直肠癌的发生、发展及预后不良相关,联合检测血清miR-96和miR-424-5p对于结直肠癌的诊断具有一定的参考价值。 Abstract:Objective To investigate the relationship between the expression of serum miR-96 and miR-424-5p and the clinicopathological characteristics and prognosis of patients with colorectal cancer (CRC), as well as explore the diagnostic value of serum miR-96 and miR-424-5p detection in CRC. Methods The serum samples of 120 patients with CRC, 40 patients with colorectal adenomas (CRAs) and 40 healthy controls from January to December 2015 in Henan Provincial People's Hospital were collected. The expression levels of miR-96 and miR-424-5p were detected by real-time quantitative PCR (RT-PCR). The relationship between the expression of miR-96 and miR-424-5p and the clinicopathological characteristics or the prognosis of patients with CRC was analysed. The receiver operating characteristic (ROC) curves were constructed to evaluate the diagnostic efficacy of serum miR-96 and miR-424-5p. Results The expression levels of serum miR-96 and miR-424-5p in patients with CRC were significantly higher than those in patients with CRA or healthy controls, with statistically significant differences (all P < 0.05). The expression level of serum miR-96 in patients with TNM stage Ⅲ/Ⅳ, low differentiation and distant metastasis was higher than those in patients with TNM Ⅰ/Ⅱ, moderate or high differentiation and without distant metastasis (all P < 0.01). The expression level of serum miR-424-5p in patients with TNM stage Ⅲ/Ⅳ was higher than that in patients with TNM Ⅰ/Ⅱ (all P < 0.01). The 5-year survival rate and mean survival time of patients with high expression of serum miR-96 and miR-424-5p were lower than those with low expression of serum miR-96 and miR-424-5p (all P < 0.01). The area under the curve (AUC) and specificity of miR-96 versus miR-424-5p in CRC were 0.727 and 71.2% versus 0.720 and 86.2%, respectively. The combined detection of AUC or specificity was 0.780 and 93.7%, which was greater than any single detection (all P < 0.05). Conclusion The increased expression levels of serum miR-96 and miR-424-5p were correlated with the occurrence, development and poor prognosis of CRC. The combined detection of serum miR-96 and miR-424-5p has significant reference value for the diagnosis of CRC. -
Key words:
- Colorectal cancer /
- MiR-424-5p /
- MiR-96 /
- Clinicopathological characteristics /
- Prognosis /
- Diagnosis value
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表 1 血清miR-96和miR-424-5p表达水平与结直肠癌临床病理特征的关系(x±s)
Table 1. Relationship between the expression levels of serum miR-96 and miR-424- 5P and clinicopathological features of colorectal cancer(x±s)
项目 例数 miR-96 t值 P值 miR-424-5p t值 P值 性别 男性 72 1.29±0.48 1.280 0.203 1.16±0.36 0.766 0.446 女性 48 1.18±0.45 1.11±0.30 年龄(岁) ≤60 58 1.25±0.46 0.212 0.832 1.12±0.34 0.429 0.669 > 60 62 1.27±0.49 1.15±0.34 肿瘤直径(cm) ≤3 55 1.25±0.54 0.269 0.789 1.13±0.37 0.167 0.867 > 3 65 1.27±0.43 1.14±0.31 肿瘤发病部位 结肠 46 1.31±0.52 0.915 0.362 1.18±0.30 1.046 0.298 直肠 74 1.23±0.44 1.11±0.36 TNM分期 Ⅰ~Ⅱ期 66 1.14±0.41 3.061 0.003 1.06±0.32 2.710 0.008 Ⅲ~Ⅳ期 54 1.40±0.52 1.23±0.33 分化程度 高/中分化 78 1.14±0.36 4.093 < 0.001 1.10±0.34 1.724 0.087 低分化 42 1.49±0.58 1.21±0.31 淋巴结转移 无 61 1.18±0.43 1.859 0.065 1.09±0.32 1.696 0.093 有 59 1.34±0.51 1.19±0.34 远处转移 无 94 1.19±0.41 3.350 0.001 1.11±0.34 1.579 0.117 有 26 1.53±0.62 1.23±0.32 -
[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[J]. CA Cancer J Clin, 2018, 68: 394-424. doi: 10.3322/caac.21492 [2] SIEGEL R L, MILLER K D, GODING SAUER A, et al. Colorectal cancer statistics, 2020[J]. CA Cancer J Clin, 2020, 70: 145-164. doi: 10.3322/caac.21601 [3] LU T X, ROTHENBERG M E. MicroRNA[J]. J Allergy Clin Immunol, 2018, 141(4): 1202-1207. doi: 10.1016/j.jaci.2017.08.034 [4] RAPADO-GONZÁLEZ Ó ÁLVAREZ-CASTRO A, LÓPEZ-LÓPEZ R, et al. Circulating microRNAs as promising biomarkers in colorectal cancer[J]. Cancers (Basel), 2019, 11(7): 898. doi: 10.3390/cancers11070898 [5] SUN Y, LIU Y, COGDELL D, et al. Examining plasma microRNA markers for colorectal cancer at different stages[J]. Oncotarget, 2016, 7(10): 11434-11449. doi: 10.18632/oncotarget.7196 [6] HE P Y, YIP W K, JABAR M F, et al. Effect of the miR-96-5p inhibitor and mimic on the migration and invasion of the SW480-7 colorectal cancer cell line[J]. Oncol Lett, 2019, 18(2): 1949-1960. [7] 胡思锋, 王庆光, 李耀锋, 等. 微小RNA-96对结直肠癌细胞迁移及侵袭的影响[J]. 中华实验外科杂志, 2019, 36(1): 83-85. doi: 10.3760/cma.j.issn.1001-9030.2019.01.026HU S F, WANG Q G, LI Y F, et al. Effect of miR-96 on migration and invasion of colorectal cancer cells[J]. Chinese Journal of Experimental Surgery, 2019, 36(1): 83-85. doi: 10.3760/cma.j.issn.1001-9030.2019.01.026 [8] GE T, XIANG P, MAO H, et al. Inhibition of miR-96 enhances the sensitivity of colorectal cancer cells to oxaliplatin by targeting TPM1[J]. Exp Ther Med, 2020, 20(3): 2134-2140. [9] DASTMALCHI N, HOSSEINPOURFEIZI M A, KHOJASTEH S M B, et al. Tumor suppressive activity of miR-424-5p in breast cancer cells through targeting PD-L1 and modulating PTEN/PI3K/AKT/mTOR signaling pathway[J]. Life Sci, 2020, 259: 118239. doi: 10.1016/j.lfs.2020.118239 [10] MA L L, LIANG L, ZHOU D, et al. Tumor suppressor miR-424-5p abrogates ferroptosis in ovarian cancer through targeting ACSL4[J]. Neoplasma, 2020, 8: 200707N705. [11] ZHAO C, ZHAO F, CHEN H, et al. microRNA-424-5p inhibits the proliferation, migration, and invasion of nasopharyngeal carcinoma cells by decreasing AKT3 expression[J]. Braz J Med Biol Res, 2020, 53(7): e9029. doi: 10.1590/1414-431x20209029 [12] 王红, 曹梦迪, 刘成成, 等. 中国人群结直肠癌疾病负担: 近年是否有变?[J]. 中华流行病学杂志, 2020, 41(10): 1633-1642. doi: 10.3760/cma.j.cn112338-20200306-00273WANG H, CAO M D, LIU C C, et al. Disease burden of colorectal cancer in China: Any changes in recent years?[J]. Chinese Journal of Epidemiology, 2020, 41(10): 1633-1642. doi: 10.3760/cma.j.cn112338-20200306-00273 [13] 吴春晓, 顾凯, 龚杨明, 等. 2015年中国结直肠癌发病和死亡情况分析[J]. 中国癌症杂志, 2020, 30(4): 241-245. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGAZ202004001.htmWU C X, GU K, GONG Y M, et al. Analysis of incidence and mortality of colorectal cancer in China, 2015[J]. China Oncology, 2020, 30(4): 241-245. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGAZ202004001.htm [14] LONG J L, HE Q L, YIN YT, et al. The effect of miRNA and autophagy on colorectal cancer[J]. Cell Prolif, 2020, 53(10): e12900. [15] YIN X L, CHAI Z T, SUN X T, et al. Overexpression of microRNA-96 is associated with poor prognosis and promotes proliferation, migration and invasion in cholangiocarcinoma cells via MTSS1[J]. Exp Ther Med, 2020, 19(4): 2757-2765. [16] NING S F, LIU H Z, GAO B, et al. miR-155, miR-96 and miR-99a as potential diagnostic and prognostic tools for the clinical management of hepatocellular carcinoma[J]. Oncol Lett, 2019, 18(3): 3381-3387. [17] CHENG Z, SHU H S, CUI Y, et al. MiR-424-5p inhibits proliferation, invasion and promotes apoptosis and predicts good prognosis in glioma by directly targeting BFAR[J]. Pathol Oncol Res, 2020, 26(4): 2327-2335. doi: 10.1007/s12253-020-00831-1 [18] YUE C F, CHEN J R, LI Z Y, et al. microRNA-96 promotes occurrence and progression of colorectal cancer via regulation of the AMPKα2-FTO-m6A/MYC axis[J]. J Exp Clin Cancer Res, 2020, 39(1): 240. doi: 10.1186/s13046-020-01731-7 [19] SAHAMI-FARD M H, KHEIRANDISH S, SHEIKHHA M H. Expression levels of miR-143-3p and miR-424-5p in colorectal cancer and their clinical significance[J]. Cancer Biomark, 2019, 24(3): 291-297. doi: 10.3233/CBM-182171