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Title: [Relationship Between the Expression of Human Matricellular Protein 3 and the Pathological Features, Drug Resistance, and Prognosis of Gastric Cancer Based on Immunohistochemical Method].
Author: Li J, Yu D, Chen S, Xie B, Wang H.
Journal: Sichuan Da Xue Xue Bao Yi Xue Ban; 2024 Jul 20; 55(4):893-901. PubMed ID: 39170027.
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 MATN3. The cells were divided into a high expression group (LV-MATN3 group) and its control group (LV-NC group) and a low expression group (sh-MATN3 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 MATN3 mRNA expression levels were measured using RT-qPCR. A nude mouse xenograft model was constructed by hypodermic injection of MGC-803 cells transfected with MATN3, and MATN3 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) (P<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 (P<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 (P<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, P<0.001; OS: log-rank=21.719, P<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 (P<0.05). Cell and animal experiments demonstrated that compared to the LV-NC group, the LV-MATN3 group exhibited significantly higher cell proliferation, migration, and invasion (P<0.05), as well as increased tumor volume and MATN3 mRNA expression in tumor tissues (P<0.05). Conversely, the sh-MATN3 group showed significantly reduced cell proliferation, migration, and invasion, along with decreased tumor volume and MATN3 mRNA levels compared to the sh-NC group (P<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. 目的: 探索胃癌患者人母系蛋白3（MATN3）表达的临床意义及其致病机制。方法: 收集2022年1月–2022年12月蚌埠医科大学第一附属医院肿瘤外科收治的胃癌患者100例，采用免疫组化法检测胃癌组织和癌旁组织的MATN3表达情况，比较各病理特征、化疗耐药与胃癌组织MATN3表达水平的关系。利用Kaplan-Meier生存曲线分析MATN3与胃癌患者无复发生存期（recurrence-free survival, RFS）和总生存期（overall survival, OS）的关系，Cox等比例风险回归分析影响胃癌患者预后的因素。转染MATN3至人胃癌细胞MGC803，将细胞分为高表达组（LV-MATN3组）及其对照（LV-NC组），低表达组（sh-MATN3组）及其对照（sh-NC组），CCK8法检测细胞增殖，Transwell实验检测细胞的迁移和侵袭，RT-qPCR检测MATN3 mRNA表达水平。将转染MATN3的MGC-803细胞注射到裸鼠皮下，构建移植瘤模型，RT-qPCR检测肿瘤组织中MATN3 mRNA表达水平。结果: 免疫组化结果显示胃癌组织MATN3高表达率〔64.00%（64/100）〕高于癌旁组织〔31.00%（31/100）〕（P<0.05）。MATN3高表达与年龄≥60岁、肿瘤部位胃体（主体胃）、肿瘤直径≥5 cm、淋巴结转移（N1～N3）、组织学分化（中高分化）、肿瘤浸润深度（T3～T4）、TNM分期（Ⅲ～Ⅳ）、远处器官有转移、有复发和死亡因素有关（P<0.05）。化疗耐药组MATN3高表达率为79.49%（31/39），高于化疗敏感组的54.10%（33/61）（P<0.05）。随访11～22个月，100例胃癌患者中有3例失访，随访率97.00%。生存曲线分析显示，MATN3高表达患者的RFS和OS低于MATN3低表达患者（P均<0.001）。Cox等比例风险回归多因素分析显示，MATN3高表达〔风险比（HR）=2.291，95%置信区间（CI）：1.268～5.392〕、肿瘤部位主体胃（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（HR=2.008，95%CI：1.049～3.902）和远处器官有转移（HR=2.505，95%CI：1.529～5.000）均为影响胃癌患者RFS和OS的独立危险因素（P<0.05）。细胞和动物实验结果显示，与LV-NC组比较，LV-MATN3组细胞增殖、迁移和侵袭能力明显升高（P<0.05），肿瘤体积以及肿瘤组织中MATN3 mRNA表达水平升高（P<0.05）；与sh-NC组比较，sh-MATN3组细胞增殖、迁移和侵袭能力降低（P<0.05），肿瘤体积缩小（P<0.05），肿瘤组织中MATN3 mRNA表达水平降低（P<0.05）。结论: MATN3参与胃癌细胞恶性行为，在胃癌组织高表达，且与病理特征、耐药性和患者不良预后相关。

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