| 摘要: |
| ［摘要］ 目的 分析结直肠癌组织及循环肿瘤细胞（CTCs）中即刻早期反应3（IER3）表达及临床意义，旨在明确IER3作为结直肠癌肿瘤标志物的应用潜力，为结直肠癌患者预后评估及靶向治疗药物研发提供参考。方法 招募2017年1月至2024年9月于广西壮族自治区人民医院接受根治性手术治疗的63例结直肠癌患者作为研究对象。收集患者的癌组织及癌旁组织，采用免疫组织化学染色和实时荧光定量聚合酶链反应（RT-qPCR）分别检测IER3蛋白表达和mRNA水平。采集患者术前1 d及术后第7天外周血，采用CanPatrol®膜过滤技术检测外周血CTCs数量及分型，并利用多重RNA原位杂交技术对CTCs中IER3 mRNA表达进行检测。采用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记（TUNEL）法评估肿瘤细胞的凋亡情况。采用电话或门诊复查形式进行随访，末次随访时间为2025年1月15日。分析IER3表达与患者肿瘤细胞凋亡程度、疾病复发和转移风险以及预后的相关性。结果 IER3蛋白在癌组织中的阳性表达率显著高于癌旁组织（90.47% vs 15.87%， χ2=10.833，P<0.001）。癌组织中IER3 mRNA相对表达量显著高于癌旁组织［（1.51±0.51） vs （1.13±0.63），t=3.200，P=0.002］。结直肠癌组织中IER3 mRNA水平与肿瘤细胞凋亡程度显著相关（P<0.05）。IER3 mRNA阳性各型CTCs数量均与浸润深度有关（P<0.05），IER3 mRNA阳性间质型CTCs数量与血管侵犯、淋巴结转移及临床分期有关（P<0.05）。随访期间无失访病例，12例因结直肠癌死亡。术后IER3 mRNA阳性上皮型CTCs数量>1的患者术后累积生存率显著低于术后IER3 mRNA阳性上皮型CTCs数量<1的患者（P<0.05）。结论 IER3在结直肠癌组织中高表达且与肿瘤细胞凋亡程度相关，各类型IER3 mRNA阳性CTCs数量可作为评估肿瘤侵袭性和预测预后的指标，有望成为结直肠癌复发转移风险分层、精准预后评估及个体化治疗的潜在生物标志物。 |
| 关键词: 结直肠癌 IER3 循环肿瘤细胞 细胞凋亡 复发转移 预后 |
| DOI：10.3969/j.issn.1674-3806.2026.06.17 |
| 分类号: |
| 基金项目:广西自然科学基金项目（编号：2023GXNSFAA026257）；广西医疗卫生适宜技术开发与推广应用项目（编号：S201642）；广西壮族自治区卫生和计划生育委员会科研课题（编号：Z20180700） |
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| Expressions of IER3 in colorectal cancer tissues and circulating tumor cells and their clinical significance |
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WEI Chunying1, LI Songlin2, ZHOU Rizhong3, QI Dengping4, ZHONG Xiaogang4
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1.Department of Dermatology, Red Cross Hospital of Yulin City, Yulin 537000, China; 2.Nanning Emergency Medical Center, Nanning 530001, China; 3.Department of Rectal and Anal Surgery, the First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning 530023, China; 4.Department of Colorectal and Anal Surgery, the People′s Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, China
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| Abstract: |
| ［Abstract］ Objective To analyze the expressions of immediate early response 3(IER3) in colorectal cancer tissues and circulating tumor cells(CTCs) and their clinical significance, and to clarify the application potential of IER3 as a tumor biomarker for colorectal cancer, and to provide reference for the prognosis assessment of colorectal cancer patients and the development of therapeutic drugs. Methods A total of 63 patients with colorectal cancer who received radical surgical treatment in the People′s Hospital of Guangxi Zhuang Autonomous Region from January 2017 to September 2024 were recruited as the research subjects. The patients′ cancer tissues and adjacent paracancerous tissues were collected. Immunohistochemistry and real-time fluorescence quantitative polymerase chain reaction(RT-qPCR) were used to detect the protein and mRNA expressions of IER3, respectively. The patients′ peripheral blood samples were collected 1 day before the operation and on the 7th day after the operation. The cell count and classification of CTCs in the peripheral blood were detected by using CanPatrol® filtration membrane technology, and the expression of IER3 mRNA in CTCs was detected by using in situ hybridization technology. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling(TUNEL) was used to evaluate tumor cell apoptosis. The follow-up was conducted through phone calls or outpatient reexaminations. The last follow-up date was January 15, 2025. The correlations of IER3 expression with the degree of tumor cell apoptosis, disease recurrence and metastatic risk, and prognosis of the patients were analyzed. Results The positive expression rate of IER3 protein in cancer tissues was significantly higher than that in adjacent paracancerous tissues(90.47% vs 15.87%, χ2=10.833, P<0.001). The relative expression level of IER3 mRNA in cancer tissues was significantly higher than that in adjacent paracancerous tissues［(1.51±0.51) vs (1.13±0.63), t=3.200, P=0.002］. The expression level of IER3 mRNA in colorectal cancer tissues was significantly correlated with the degree of tumor cell apoptosis(P<0.05). The cell count of IER3 mRNA-positive CTCs in each subtype was correlated with the depth of tumor invasion(P<0.05), whereas the cell count of IER3 mRNA-positive mesenchymal CTCs was correlated with vascular invasion, lymph node metastasis and clinical stages(P<0.05). No patients in this study were lost to follow-up, among whom 12 patients died of colorectal cancer. The patients with the postoperative cell count of IER3 mRNA-positive epithelial CTCs>1 exhibited significantly lower postoperative cumulative survival rate than those with the postoperative cell count of IER3 mRNA-positive epithelial CTCs<1(P<0.05). Conclusion IER3 is highly expressed in colorectal cancer tissues and correlated with the degree of tumor cell apoptosis. The cell count of IER3 mRNA-positive CTCs in various subtypes can serve as indicators for evaluating tumor invasiveness and predicting prognosis, and IER3 is expected to be a potential biomarker for risk stratification of recurrence and metastasis, precise prognostic assessment and individualized treatment of colorectal cancer. |
| Key words: Colorectal cancer Immediate early response 3(IER3) Circulating tumor cells Apoptosis Recurrence and metastasis Prognosis |
