miR-544a在结直肠癌组织中的表达及其意义

doi:10.3969/j.issn.1004-616x.2024.02.007

摘要/Abstract

摘要： 目的：探讨结直肠癌患者组织中微小RNA-544a(miR-544a)的表达水平及其与患者预后的关系。方法：选取2016年1月—2019年2月住院并接受手术的150例结直肠癌患者，采用实时荧光定量PCR法检测癌组织中miR-544a的表达情况，免疫组织化学法检测癌组织中Ki67、CD4、CD8表达情况。Mann-Whitney U检验、卡方检验和Fisher精确检验分析癌组织中miR-544a表达水平与患者临床病理指标的关系。单因素和多因素 Cox 回归分析影响结直肠癌预后的因素。Kaplan-Meier 法分析结直肠癌组织中miR-544a表达水平与患者无病生存期(DFS)、总生存期(OS)的关系。结果：结直肠癌组织中 miR-544a相对表达水平为 1.85±0.15，高于癌旁正常组织的1.06±0.21，差异具有统计学意义(P<0.01)。miR-544a表达水平与周围神经侵犯率、T分期、N分期有关(均为P<0.01)，miR-544a高表达组神经侵犯率高，T、N分期较晚。免疫组织化学检测结果显示，miR-544a高表达组Ki67评分为120.2±33.7，低表达组Ki67评分为112.4±40.8，两组差异无统计学意义(P>0.05)；miR-544a高表达组患者CD4、CD8评分分别为15.5±5.3和 24.8±7.6，均低于 miR-544a低表达组(分别为 21.3±7.2和 29.6±8.9)，差异均具有统计学意义(均为 P<0.05)。单因素、多因素 Cox回归分析显示肿瘤N、M分期及miR-544a表达水平与CRC患者根治术后DFS、OS显著相关(均为 P<0.01)。结论：结直肠癌组织中miR-544a表达水平上调，miR-544a高表达与结直肠癌患者较晚的N、M分期以及不良预后有关，且miR-544a可能是反映免疫治疗效果的潜在标志物。

关键词: 结直肠癌, 微小RNA, miR-544a, 预后, 肿瘤标志物

Abstract: OBJECTIVE： To explore expression level and clinical prognostic value of microRNA-544a (miR-544a) in tissues of colorectal cancer patients. METHODS：From January 2016 to February 2019， 150 patients with colorectal cancer were selected. Real time fluorescence quantitative PCR was used to detect expression levels of miR-544a in tissues， and immunohistochemistry was used to detect the expression of Ki67，CD4，and CD8 in tissues. Mann Whitney U-test，chi square test，and Fisher′s exact test were used to analyze relationships between miR-544a expression level in cancer tissue and clinical pathological indicators of patients. Univariate and multivariate Cox regressions were used to analyze factors affecting the prognosis of colorectal cancer. The Kaplan-Meier method was used to analyze relationships between expression levels of miR-544a in tissues and disease-free survival (DFS) and overall survival (OS) of patients. RESULTS： The relative expression level of miR-544a in colorectal cancer tissue (1.85±0.15) was significantly higher than that in the adjacent normal tissues (1.06 ± 0.21) (P<0.01). The expression level of miR-544a was related to the incidence of peripheral nerve invasion，T staging，and N staging (all P<0.01)，while the high expression group of miR-544a had a higher incidence of nerve invasion and a later T and N staging. The immunohistochemical results showed that the Ki67 score of the miR-544a high expression group was 120.2±33.7，while the Ki67 score of the low expression group was 112.4±40.8，with no significant difference between the two groups (P> 0.05). The CD4 and CD8 scores of patients in the miR-544a high expression group were 15.5±5.3 and 24.8± 7.6， respectively， lower than those in the miR-544a low expression group (21.3 ± 7.2 and 29.6 ± 8.9， respectively)， with statistically significant differences (all P<0.05). Univariate and multivariate COX regression showed significant correlations between tumor N，M staging，and miR-544a expression levels and postoperative DFS and OS in CRC patients (all P<0.01). CONCLUSION： Upregulation of miR-544a expression in colorectal cancer tissue may be associated with delayed N and M stagings in colorectal cancer patients，and miR-544a may be a potential biomarker for immunotherapy efficacy.

Key words: colorectal cancer, miRNA, miR-544a, prognosis, tumor biomarker

中图分类号:

R735.3

童晶, 王丹. miR-544a在结直肠癌组织中的表达及其意义[J]. 癌变·畸变·突变, 2024, 36(2): 124-128,137.

TONG Jing, WANG Dan. Expression and significance of miR-544a in patients with colorectal cancer[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2024, 36(2): 124-128,137.

参考文献

[1] ZHENG R, ZHANG S W, ZENG H, et al. Cancer incidence and mortality in China, 2016[J]. J Nation Cancer Center, 2022, 2(1):1-9.
[2] KOULOURIS A, TSAGKARIS C, MESSARITAKIS I, et al. Resectable colorectal cancer:current perceptions on the correlation of recurrence risk, microbiota and detection of genetic mutations in liquid biopsies[J]. Cancers, 2021, 13(14):3522.
[3] IMAI K, BENITEZ C C, ALLARD M A, et al. Impact of surgical treatment for recurrence after 2-stage hepatectomy for colorectal liver metastases, on patient outcome[J]. Ann Surg, 2019, 269(2):322-330.
[4] HE B X, ZHAO Z Y, CAI Q D, et al. miRNA-based biomarkers, therapies, and resistance in cancer[J]. Int J Biol Sci, 2020, 16(14):2628-2647.
[5] ZHANG N, HU X Y, DU Y N, et al. The role of miRNAs in colorectal cancer progression and chemoradiotherapy[J]. Biomed Pharmacother, 2021, 134:111099.
[6] AZARI H, KARIMI E, SHEKARI M, et al. Construction of a lncRNA-miRNA-mRNA network to determine the key regulators of the Th1/Th2 imbalance in multiple sclerosis[J]. Epigenomics, 2021, 13(22):1797-1815.
[7] MA X M, MA T, CHANG L, et al. Correlation between miRNA-124, miRNA-544a, and TNF-α levels in acute spinal cord injury[J]. Spinal Cord, 2022, 60(9):779-783.
[8] HE Q R, ZHAO L N, LIU Y H, et al. Circ-SHKBP1 regulates the angiogenesis of U87 glioma-exposed endothelial cells through miR-544a/FOXP1 and miR-379/FOXP2 pathways[J]. Mol Ther Nucleic Acids, 2018, 10:331-348.
[9] LU P W, GU Y T, LI L, et al. miR-544a promotes breast cancer cell migration and invasion reducing cadherin 1 expression[J]. Oncol Res, 2016, 23(4):165-170.
[10] MO X M, ZHANG F H, LIANG H, et al. miR-544a promotes the invasion of lung cancer cells by targeting cadherina 1 in vitro[J]. Onco Targets Ther, 2014, 7:895-900.
[11] YANAKA Y, MURAMATSU T, UETAKE H, et al. miR-544a induces epithelial-mesenchymal transition through the activation of WNT signaling pathway in gastric cancer[J]. Carcinogenesis, 2015, 36(11):1363-1371.
[12] ZHENG W P, MENG F L, WANG L Y. miR-544a Stimulates endometrial carcinoma growth via targeted inhibition of reversion-inducing cysteine-rich protein with Kazal motifs[J]. Mol Cell Probes, 2020, 53:101572.
[13] SUN S F, SU C Y, ZHU Y X, et al. microRNA-544a regulates migration and invasion in colorectal cancer cells via regulation of homeobox A10[J]. Dig Dis Sci, 2016, 61(9):2535-2544.
[14] ZHANG L F, LIU L Y, LI X. miR-526b-3p mediates doxorubicin-induced cardiotoxicity by targeting STAT3 to inactivate VEGFA[J]. Biomed Pharmacother, 2020, 123:109751.
[15] PIERCEALL W E, WOLFE M, SUSCHAK J, et al. Strategies for H-score normalization of preanalytical technical variables with potential utility to immunohistochemical-based biomarker quantitation in therapeutic response diagnostics[J]. Anal Cell Pathol (Amst), 2011, 34(3):159-168.
[16] MESSERSMITH W A. NCCN guidelines updates:management of metastatic colorectal cancer[J]. J Natl Compr Cancer Netw, 2019, 17(5.5):599-601.
[17] PAIJENS S T, VLEDDER A, DE BRUYN M, et al. Tumorinfiltrating lymphocytes in the immunotherapy era[J]. Cell Mol Immunol, 2021, 18(4):842-859.
[18] OSTROUMOV D, FEKETE-DRIMUSZ N, SABOROWSKI M, et al. CD4 and CD8 T lymphocyte interplay in controlling tumor growth[J]. Cell Mol Life Sci, 2018, 75(4):689-713.