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基于免疫组织化学方法的人基质细胞蛋白3表达与胃癌病理特征、耐药性及预后的关系

[Relationship Between the Expression of Human Matricellular Protein 3 and the Pathological Features, Drug Resistance, and Prognosis of Gastric Cancer Based on Immunohistochemical Method].

作者信息

Li Jing, Yu Dajun, Chen Shaohua, Xie Bo, Wang Hu

机构信息

( 233000) Department of Surgical Oncology, The First Affiliated Hospital of Bengbu Medical University, Bengbu 233000, China.

出版信息

Sichuan Da Xue Xue Bao Yi Xue Ban. 2024 Jul 20;55(4):893-901. doi: 10.12182/20240760205.

Abstract

OBJECTIVE

To observe the relationship between the expression of human matricellular protein 3 (MATN3) and the pathological features, drug resistance, and prognosis of gastric cancer based on immunohistochemical method.

METHODS

A total of 100 gastric cancer patients treated at the First Affiliated Hospital of Bengbu Medical College from January 2022 to December 2022 were included. MATN3 expression in gastric cancer tissues and paracancerous tissues was assessed by immunohistochemistry. The expression of MATN3 was compared across pathological features. Patients were divided into sensitive and resistant groups based on chemotherapy resistance, and MATN3 expression was compared between these groups. The relationship between MATN3 and recurrence-free survival (RFS) and overall survival (OS) of gastric cancer patients was analyzed using Kaplan-Meier survival curves. Univariate and multifactorial Cox regression analyses were used to analyze the factors affecting the prognosis of gastric cancer patients. Human gastric cancer cells MGC803 were transfected with . The cells were divided into a high expression group (LV- group) and its control group (LV-NC group) and a low expression group (sh- group) and its control group (sh-NC group). Cell proliferation was assessed using the CCK8 assay, cell migration and invasion were assessed using the Transwell assay, and mRNA expression levels were measured using RT-qPCR. A nude mouse xenograft model was constructed by hypodermic injection of MGC-803 cells transfected with , and mRNA expression levels in tumor tissues were measured using RT-qPCR.

RESULTS

Immunohistochemical results showed a significantly higher rate of high MATN3 expression in gastric cancer tissues (64.00%, 64/100) compared to adjacent non-cancerous tissues (31.00%, 31/100) (<0.05). High MATN3 expression was associated with age ≥60 years old, tumor location in the gastric body, tumor size ≥5 cm, lymph node metastasis (N1-N3), histological differentiation (moderate to high), tumor invasion depth (T3-T4), TNM stage (Ⅲ-Ⅳ), distant organ metastasis, recurrence, and mortality (<0.05). Among patients with chemotherapy resistance, the high MATN3 expression rate was 79.49% (31/39) in the resistant group compared to 54.10% (33/61) in the sensitive group (<0.05). Follow-up duration ranged from 11 to 22 months, with a 97.00% follow-up rate and 3 cases lost to follow-up. Kaplan-Meier survival curve analysis showed that patients with high MATN3 expression had significantly lower RFS and OS compared to those with low MATN3 expression (RFS: log-rank=17.291, <0.001; OS: log-rank=21.719, <0.001). Multivariate Cox analysis identified high MATN3 expression (hazard ratio [HR]=2.291, 95% confidence interval [CI]: 1.268-5.392), tumor location in the gastric body (HR=2.057, 95% CI: 1.441-5.666), lymph node metastasis (N1-N3) (HR=2.011, 95% CI: 1.010-2.274), tumor invasion depth (T3-T4) (H=2.977, 95% CI: 1.032-7.853), TNM stage Ⅲ-Ⅳ (HR=2.008, 95% CI: 1.049-3.902), and distant organ metastasis (HR=2.505, 95% CI: 1.529-5.000) as independent risk factors affecting RFS and OS (<0.05). Cell and animal experiments demonstrated that compared to the LV-NC group, the LV- group exhibited significantly higher cell proliferation, migration, and invasion (<0.05), as well as increased tumor volume and mRNA expression in tumor tissues (<0.05). Conversely, the sh- group showed significantly reduced cell proliferation, migration, and invasion, along with decreased tumor volume and mRNA levels compared to the sh-NC group (<0.05).

CONCLUSION

MATN3 is highly expressed in gastric cancer tissues and is associated with various pathological features, drug resistance and poor prognosis. MATN3 holds potential as a diagnostic marker for poor prognosis and may play a role in the malignant behaviors of gastric cancer cells, including proliferation, migration, and invasion.

摘要

目的

基于免疫组化方法观察人基质细胞蛋白3(MATN3)表达与胃癌病理特征、耐药性及预后的关系。

方法

纳入2022年1月至2022年12月在蚌埠医学院第一附属医院接受治疗的100例胃癌患者。采用免疫组化法评估胃癌组织和癌旁组织中MATN3的表达。比较不同病理特征下MATN3的表达情况。根据化疗耐药性将患者分为敏感组和耐药组,比较两组间MATN3的表达。采用Kaplan-Meier生存曲线分析MATN3与胃癌患者无复发生存期(RFS)和总生存期(OS)的关系。采用单因素和多因素Cox回归分析影响胃癌患者预后的因素。将人胃癌细胞MGC803进行转染。细胞分为高表达组(LV-组)及其对照组(LV-NC组)和低表达组(sh-组)及其对照组(sh-NC组)。采用CCK8法评估细胞增殖,采用Transwell法评估细胞迁移和侵袭,采用RT-qPCR法检测mRNA表达水平。通过皮下注射转染后的MGC-803细胞构建裸鼠异种移植模型,采用RT-qPCR法检测肿瘤组织中mRNA表达水平。

结果

免疫组化结果显示,胃癌组织中MATN3高表达率(64.00%,64/100)显著高于癌旁非癌组织(31.00%,31/100)(P<0.05)。MATN3高表达与年龄≥60岁、肿瘤位于胃体、肿瘤大小≥5 cm、淋巴结转移(N1-N3)、组织学分化(中至高分化)、肿瘤浸润深度(T3-T4)、TNM分期(Ⅲ-Ⅳ期)、远处器官转移、复发及死亡相关(P<0.05)。在化疗耐药患者中,耐药组MATN3高表达率为79.49%(31/39),敏感组为54.10%(33/61)(P<0.05)。随访时间为11至22个月,随访率为97.00%,失访3例。Kaplan-Meier生存曲线分析显示,MATN3高表达患者的RFS和OS显著低于MATN3低表达患者(RFS:log-rank=17.291,P<0.001;OS:log-rank=21.719,P<0.001)。多因素Cox分析确定MATN3高表达(风险比[HR]=2.291,95%置信区间[CI]:1.268-5.392)、肿瘤位于胃体(HR=2.057,95%CI:1.441-5.666)、淋巴结转移(N1-N3)(HR=2.011,95%CI:1.010-2.274)、肿瘤浸润深度(T3-T4)(HR=2.977,95%CI:1.032-7.853)、TNM分期Ⅲ-Ⅳ期(HR=2.008,95%CI:1.049-3.902)及远处器官转移(HR=2.505,95%CI:1.529-5.000)为影响RFS和OS的独立危险因素(P<0.05)。细胞和动物实验表明,与LV-NC组相比,LV-组细胞增殖、迁移和侵袭显著增加(P<0.05),肿瘤体积和肿瘤组织中mRNA表达增加(P<0.05)。相反,与sh-NC组相比,sh-组细胞增殖、迁移和侵袭显著降低,肿瘤体积和mRNA水平降低(P<0.05)。

结论

MATN3在胃癌组织中高表达,与多种病理特征、耐药性及预后不良相关。MATN3有望作为预后不良的诊断标志物,并可能在胃癌细胞的增殖、迁移和侵袭等恶性行为中发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7454/11334280/4a1ed4b8b2f3/scdxxbyxb-55-4-893-1.jpg

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