■观察人体细胞蛋白3(MATN3)的表达与病理特征之间的关系,耐药性,基于免疫组织化学方法的胃癌预后。
■纳入了2022年1月至2022年12月在蚌埠医学院第一附属医院治疗的100例胃癌患者。免疫组化法检测MATN3在胃癌组织和癌旁组织中的表达。在病理特征之间比较MATN3的表达。根据化疗耐药情况将患者分为敏感组和耐药组,并比较这些组之间的MATN3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。用MATN3转染人胃癌细胞MGC803。将细胞分为高表达组(LV-MATN3组)及其对照组(LV-NC组)和低表达组(sh-MATN3组)及其对照组(sh-NC组)。使用CCK8测定法评估细胞增殖,使用Transwell测定法评估细胞迁移和侵袭,使用RT-qPCR测量MATN3mRNA表达水平。通过皮下注射MATN3转染的MGC-803细胞构建裸鼠异种移植模型,并使用RT-qPCR测量肿瘤组织中MATN3mRNA的表达水平。
■免疫组化结果显示,MATN3在胃癌组织中的高表达率(64.00%,64/100)与邻近非癌组织相比(31.00%,31/100)(P<0.05)。MATN3高表达与年龄≥60岁有关,肿瘤在胃体的位置,肿瘤大小≥5cm,淋巴结转移(N1-N3),组织学分化(中度至高度),肿瘤浸润深度(T3-T4),TNM分期(Ⅲ-Ⅳ期),远处器官转移,复发,死亡率(P<0.05)。在化疗耐药的患者中,抗性组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11~22个月,随访率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明显低于MATN3低表达患者(RFS:log-rank=17.291,P<0.001;OS:log-rank=21.719,P<0.001)。多变量Cox分析确定了MATN3的高表达(风险比[HR]=2.291,95%置信区间[CI]:1.268-5.392),肿瘤在胃体中的位置(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)(H=2.977,95%CI:1.032-7.853),TNM分期Ⅲ-Ⅳ期(HR=2.008,95%CI:1.049-3.902),远处器官转移(HR=2.505,95%CI:1.529~5.000)是影响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-MATN3组表现出明显更高的细胞增殖,迁移,和侵袭(P<0.05),以及肿瘤体积和肿瘤组织中MATN3mRNA表达增加(P<0.05)。相反,sh-MATN3组细胞增殖明显减少,迁移,和入侵,与sh-NC组相比,肿瘤体积和MATN3mRNA水平降低(P<0.05)。
■MATN3在胃癌组织中高表达,与多种病理特征有关,耐药及预后不良。MATN3有可能作为不良预后的诊断标志物,并可能在胃癌细胞的恶性行为中起作用。包括扩散,迁移,和入侵。
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.