[1]段世举.甲胎蛋白阴性肝癌患者血清外泌体circ RNA100338 和CRNDE 表达水平及预后预测价值研究[J].现代检验医学杂志,2023,38(05):63-69.[doi:10.3969/j.issn.1671-7414.2023.05.012]
　DUAN Shiju.Study on the Expression Level and Prognostic Value of Serum Exosomes Circ RNA100338 and CRNDE in Patients with Alpha-fetoprotein Negative Hepatocellular Carcinoma[J].Journal of Modern Laboratory Medicine,2023,38(05):63-69.[doi:10.3969/j.issn.1671-7414.2023.05.012]
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甲胎蛋白阴性肝癌患者血清外泌体circ RNA100338 和CRNDE 表达水平及预后预测价值研究()
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《现代检验医学杂志》[ISSN:/CN:]

卷:
第38卷
期数:
2023年05期
页码:
63-69
栏目:
论著
出版日期:
2023-09-15

文章信息/Info

Title:
Study on the Expression Level and Prognostic Value of Serum Exosomes Circ RNA100338 and CRNDE in Patients with Alpha-fetoprotein Negative Hepatocellular Carcinoma
文章编号:
1671-7414（2023）05-063-07
作者:
段世举
（联勤保障部队第九四二医院检验病理科，银川 750001）
Author(s):
DUAN Shiju
（Department of Clinical Laboratory and Pathology, Joint Service Support Force 942 Hospital, Yinchuan 750001, China）
关键词:
血清外泌体; 环状核糖核酸100338; 结直肠肿瘤差别表达; 甲胎蛋白阴性肝细胞癌
分类号:
R735.7；730.43
DOI:
10.3969/j.issn.1671-7414.2023.05.012
文献标志码:
A
摘要:
目的 研究甲胎蛋白阴性肝细胞癌(AFP-NHCC）患者血清外泌体环状RNA（circ RNA）100338，长链非编码RNA 结直肠肿瘤差别表达 (colorectal neoplasia differentially expressed，CRNDE) 基因表达及临床预后价值。方法 选取自2018 年1 月～ 2019 年7 月期间联勤保障部队第九四二医院诊治的AFP-NHCC 患者98 例为研究对象，以同期健康体检的70 例健康人作为对照组。实时荧光定量PCR 检测血清外泌体circ RNA 100338 和CRNDE 水平。比较不同临床病理特征AFP-NHCC 患者血清外泌体circ RNA 100338 和CRNDE 水平。受试者工作特征曲线（ROC）分析外泌体circ RNA 100338，CRNDE 评估BCLC 分期B ～ C 期、低分化程度及肝内淋巴结转移的临界值。Kaplan-Meier 生存分析（Log-Rank 检验）分析血清外泌体circ RNA 100338，CRNDE 对AFP-NHCC 患者生存预后的影响。单因素及多因素COX 回归分析影响AFP-NHCC 患者预后的因素。结果 AFP-NHCC 组患者血清外泌体circ RNA100338（2.78±0.67），CRNDE 的相对表达量（3.05±0.70） 高于对照组（0.92±0.31，1.06±0.29）， 差异具有统计学意义（t=21.619，22.435，均P ＜ 0.05）。AFP-NHCC 组患者血清外泌体circ RNA100338 与CRNDE 表达呈显著正相关性（r=0.657，P ＜ 0.05）。BCLC 分期B ～ C 期（3.43±0.69 ，3.71±0.75）、低分化程度（3.64±0.73，4.27±0.74）及并发肝内淋巴结转移（3.96±0.79，4.39±0.76）AFP-NHCC 患者血清外泌体circ RNA100338，CRNDE 表达分别高于BCLC 分期0 ～ A 期（1.87±0.60，2.13±0.61）、高中分化程度（2.02±0.64，1.97±0.61）及无肝内淋巴结转移（2.03±0.60，2.20±0.65）患者，差异均有统计学意义（t=11.648，11.707，13.699；11.100，16.857，15.211，均P ＜ 0.05）。外泌体circ RNA100338 评估BCLC 分期B ～ C 期、低分化程度及肝内淋巴结转移的临界值分别为3.51，3.69 和4.06，外泌体CRNDE 评估BCLC 分期B ～ C 期、低分化程度及肝内淋巴结转移的临界值分别为3.79，4.31 和4.45。circ RNA100338高表达组和低表达组患者三年总体生存率分别为52.08%（25/48）和86.00%（43/50）。circ RNA 100338 高表达组患者累积生存率低于低表达组患者，差异有统计学意义(Log-Rank χ2=12.490, P ＜ 0.05)。CRNDE 高表达组和低表达组患者三年总体生存率分别为51.06%（24/47）和86.27%（44/51）。CRNDE 高表达组患者累积生存率低于低表达组患者，差异有统计学意义(Log-Rank χ2=15.050, P ＜ 0.05)。肿瘤BCLC 分期B ～ C（OR=1.405，P ＜ 0.05）、低分化程度（OR=1.921，P ＜ 0.05）、有肝内淋巴结转移（OR=1.508，P ＜ 0.05），circ RNA100338 高表达（OR=1.906，P ＜ 0.05）及CRNDE高表达（OR=1.733，P ＜ 0.05）是影响AFP-NHCC 患者预后的独立危险因素。结论 AFP-NHCC 患者血清外泌体circRNA 100338，CRNDE 表达升高，两者表达与肿瘤BCLC 分期、病理分化程度及肝内淋巴结转移有关，是影响AFPNHCC患者生存预后的独立危险因素。
Abstract:
Objective To study the expression of serum exosomes circ RNA (circ RNA) 100338 and long chain non-coding RNA colorectal neoplasia differentially expressed(CRNDE) in alpha fetoprotein negative hepatocellular carcinoma (AFP-NHCC) and their clinical prognostic value. Methods 98 patients with AFP-NHCC diagnosed and treated in the Joint Service Support Force 942 Hospital from January 2018 to July 2019 were selected as the study object, and 70 healthy people in the same period were selected as the control group. The levels of circ RNA100338 and CRNDE in serum exosomes were detected by real-time fluorescent quantitative PCR, and the serum exocrine circ RNA100338 and CRNDE levels in AFP-NHCC patients with different clinical features were compared. The receiver operating curve (ROC) was used to analyze the cutoff value of exosomes circ RNA100338, CRNDE in evaluating the BCLC stage B to C, the degree of poor differentiation, and the critical value of intrahepatic lymph node metastasis. Kaplan Meier survival analysis (Log Rank test) was used to analyze the effect of serum exosome circ RNA100338 and CRNDE expression on the prognosis of AFP NHCC patients. Univariate and multivariate COX regression analysis was used to analyze factors affecting the prognosis of patients with AFP-NHCC. Results The relative expression of serum exosomes circ RNA100338 and CRNDE in patients with AFP-NHCC group (2.78 ± 0.67, 3.05 ± 0.70) was significantly higher than that in the control group（0.92±0.31，1.06±0.29），and the differences were statistically significant (t=21.619, 22.435, all P<0.05). There was a significant positive correlation between circ RNA100338 and CRNDE expression in serum exosomes of AFP-NHCC group (r=0.657, P<0.05). The expression of serum exosomes circ RNA100338 and CRNDE in AFP-NHCC patients with BCLC stage B ～ C（3.43±0.69, 3.71±0.75）, low differentiation （3.64±0.73, 4.27±0.74）and intrahepatic lymph node metastasis （3.96±0.79, 4.39±0.76）were significantly higher than those in patients with BCLC stage 0 ～ A（1.87±0.60, 2.13±0.61）, high and middle differentiation （2.02±0.64，1.97±0.61）and no intrahepatic lymph node metastasis（2.03±0.60, 2.20±0.65），and the differences were statistically significant（t=11.648， 11.707, 13.699; 11.100, 16.857, 15.211, all P ＜ 0.05）. The cut-off values for evaluating BCLC stage B ～ C, poorly differentiated degree, and intrahepatic lymph node metastasis were 3.51，3.69，and 4.06 for exosomes circ RNA 100338. The cut-off values for evaluating BCLC stage B ～ C, poorly differentiated degree, and intrahepatic lymph node metastasis for exosomes CRNDE were 3.79, 4.31, and 4.45, respectively. The 3-year overall survival rates of patients with high and low expression of circ RNA100338 were 52.08% (25/48) and 86.00% (43/50), respectively. The cumulative survival of patients with high expression of circ RNA100338 was lower than that of patients with low expression, with a statistically significant difference (Log rank χ2=12.490, P<0.05). The 3-year overall survival rates of patients with high and low CRNDE expression were 51.06% (24/47) and 86.27% (44/51), respectively. The cumulative survival of patients with high CRNDE expression was lower than that of patients with low CRNDE expression (Log rank χ2=15.050, P<0.05). BCLC staging of tumor B ～ C (OR=1.405, P<0.05), low differentiation (OR=1.921, P<0.05), intrahepatic lymph node metastasis (OR=1.508, P<0.05), high expression of circ RNA100338 (OR=1.906, P<0.05) and high expression of CRNDE (OR=1.733, P<0.05) were independent risk factors affecting the prognosis of AFP-NHCC patients. Conclusion The expression of circ RNA100338 and CRNDE in serum exosome of patients with AFP-NHCC were increased, which were related to the BCLC stage, pathological differentiation and intrahepatic lymph node metastasis of tumor, and are independent risk factors for survival and prognosis of patients with AFP-NHCC.

参考文献/References:

[1] KULIK L, EL-SERAG H B. Epidemiology and management of hepatocellular carcinoma[J].Gastroenterology, 2019, 156(2): 477-491, e1.
[2] LI Wencui, HAN Lizhu, XIAO Bohan, et al. A predictive nomogram of early recurrence for patients with AFP-negative hepatocellular carcinoma underwent curative resection[J]. Diagnostics（Basel Switzerland）,2022,12(5): 1073.
[3] ZHANG Lin, YU Dihua. Exosomes in cancer development, metastasis, and immunity[J]. Biochim Biophys Acta Rev Cancer, 2019, 1871(2): 455-468.
[4] MANSOURY F, BABAEI N, ABDI S, et al. Extremely low frequency magnetic fields induce mTOR and Hsa_ Circ RNA_100338 expression changes in gastric cancer and normal fibroblast cell lines[J]. Cell Journal, 2022, 24(7): 364-369.
[5] ZHOU Yujun, MAO Xingkang, PENG Rui, et al. Circ RNAs in hepatocellular carcinoma: characteristic, functions and clinical significance[J]. International Journal of Medical Sciences, 2022, 19(14): 2033-2043.
[6] JING Hongyu, XIA Huan, QIAN Ming, et al. Long noncoding RNA CRNDE promotes non-small cell lung cancer progression via sponging microRNA-338-3p[J].Biomedicine & Pharmacotherapy, 2019, 110: 825-833.
[7] JI Degang, JIANG Chengwei, ZHANG Lirong, et al. LncRNA CRNDE promotes hepatocellular carcinoma cell proliferation, invasion, and migration through regulating miR-203/ BCAT1 axis[J]. Journal of Cellular Physiology, 2019, 234(5): 6548-6560.
[8] 游幼匡, 段少银．肝内胆管癌与甲胎蛋白阴性肝细胞肝癌的MRI 影像特征对照分析[J]．中国中西医结合影像学杂志, 2020, 18（6）：614-617． YOU Youkuang, DUAN Shaoyin. Comparative analysis of MRI features of intrahepatic cholangiocarcinoma and AFP negative hepatocellular carcinoma[J]. Chinese Imaging Journal of Integrated Traditional and Western Medicine, 2020, 18(6): 614-617.
[9] 黄德发, 陈杰, 杨通, 等．三种方法提取血清外泌体的比较研究[J]．现代检验医学杂志, 2021, 36（6）：139-142． HUANG Defa, CHEN Jie, YANG Tong, et al. Comparative study on three methods for extraction of serum exosomes[J]. Journal of Modern Laboratory Medicine, 2021, 36(6): 139-142.
[10] CHANG H, LI Z B, WU J Y, et al. Circ RNA-100338 induces angiogenesis after myocardial ischemiareperfusion injury by sponging miR-200a-3p[J].European Review for Medical and Pharmacological Sciences, 2020, 24(11): 6323-6332.
[11] CHENG Xiaoli, TIAN Pan, ZHENG Wengzhong, et al. Piplartine attenuates the proliferation of hepatocellular carcinoma cells via regulating hsa_circ_100338 expression [J]. Cancer Medicine, 2020, 9(12): 4265-4273.
[12] HUANG Xiuyan, HUANG Zili, XU Yonghua, et al. Comprehensive circular RNA RNA profiling reveals the regulatory role of the circ RNA-100338/miR-141-3p pathway in hepatitis B-related hepatocellular carcinoma[J]. Scientific Reports, 2017, 7(1): 5428.
[13] HUANG Xiuyan, HUANG Zili, ZHANG Pingbao, et al. CircRNA-100338 is associated with mTOR signaling pathway and poor prognosis in hepatocellular carcinoma [J]. Frontiers in Oncology, 2019, 9: 392.
[14] HANNA G K, MADANY M, TAY A S S, et al. ZEB1 loss increases glioma stem cell tumorigenicity and resistance to chemoradiation [J]. Journal of Neurosurgery, 2022, 138(5):1313-1324.
[15] SONG Lairong, LI Xiaojie, XU Xiaoying, et al. Comprehensive analysis of the prognostic value and molecular function of CRNDE in glioma at bulk and single-cell levels[J]. Cells, 2022, 11(22): 3669.
[16] LIU Y C, LIN Y H, CHI H C, et al. CRNDE acts as an epigenetic modulator of the p300/YY1 complex to promote HCC progression and therapeutic resistance[J].Clinical Epigenetics, 2022, 14(1): 106.
[17] LIN Chao, XIANG Yien, SHENG Jiyao, et al. Long non-coding RNA CRNDE promotes malignant progression of hepatocellular carcinoma through the miR-33a-5p/CDK6 axis[J]. Journal of Physiology and Biochemistry, 2020, 76(3): 469-481.
[18] CHEN Lingxi, SUN Liangbo, DAI Xufang, et al. LncRNA CRNDE promotes ATG4B-mediated autophagy and alleviates the sensitivity of sorafenib in hepatocellular carcinoma cells[J]. Frontiers in Cell and Developmental Biology, 2021, 9: 687524.
[19] ZHANG Feifei, WANG Hui, YU Jiang, et al. LncRNA CRNDE attenuates chemoresistance in gastric cancer via SRSF6-regulated alternative splicing of PICALM[J]. Molecular Cancer, 2021, 20(1): 6.
[20] TAKAHASHI S, NORO R, SEIKE M, et al. Long noncoding RNA CRNDE is involved in resistance to EGFR tyrosine kinase inhibitor in EGFR-mutant lung cancer via eIF4A3/MUC1/EGFR signaling[J]. International Journal of Molecular Sciences, 2021, 22(8): 4005.
[21] KLINGE C M. Non-coding RNAs in breast cancer: intracellular and intercellular communication[J]. Non Coding RNA, 2018, 4(4): 40.

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备注/Memo

备注/Memo:
基金项目：宁夏回族自治区科技支撑计划项目（XT201817）：多个血清指标联合对于甲胎蛋白阴性肝癌患者术后预后价值分析。
作者简介：段世举（1988-），男，本科，主管技师，主要从事分子生物与微生物研究，E-mail：duanshiju665@163.com。
更新日期/Last Update: 2023-09-15