Expression and Prognostic Value of miR-145-5p and FSCN1 in Gastric Cancer Tissues
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摘要:
目的 探讨微小RNA-145-5p（miR-145-5p）、肌成束蛋白-1（fascin actin-bundling protein-1，FSCN1）在胃癌组织中的表达及生存预测价值。 方法 选取邯郸市第一医院2019年8月—2021年8月收治的胃癌患者103例。对患者癌组织及癌旁组织FSCN1mRNA、miR-145-5p表达进行检测并分析，使用Pearson分析评估miR-145-5p、FSCN1 mRNA表达的相关性，受试者工作特征曲线下面积（area under the curve，AUC）评估miR-145-5p、FSCN1 mRNA对胃癌患者预后的预测价值；Cox比例风险回归模型对不良预后影响因素进行分析，并采用Kaplan-Meier法进行生存分析。 结果 与癌旁组织比较，癌组织的miR-145-5p表达水平降低（P < 0.05），FSCN1 mRNA表达升高（P<0.05）。与高分化、肿瘤分期I+II期、浸润深度T1～T2、无淋巴结转移、肿瘤最大直径<5 cm癌组织比较，低中分化、肿瘤分期III+IV期、浸润深度T3～T4、有淋巴结转移、肿瘤最大直径≥5 cm的癌组织 miR-145-5p表达水平降低，而FSCN1 mRNA表达升高（P < 0.05）。Pearson分析显示，miR-145-5p与FSCN1 mRNA表达在患者癌组织中为负相关关系（r = -0.617，P = 0.000）。COX多因素回归分析表明，低中分化、肿瘤分期III+IV期、肿瘤最大直径≥5 cm、浸润深度T3～T4、miR-145-5p低表达、FSCN1 mRNA高表达、有淋巴结转移是胃癌不良预后的危险因素（P < 0.05）。Kaplan-Meier生存曲线表明，miR-145-5p低表达组与miR-145-5p高表达组3年总生存率差异有统计学意义（P < 0.05）。FSCN1 mRNA低表达组与FSCN1 mRNA高表达组3年总生存率差异有统计学意义（P < 0.05）。ROC曲线分析结果显示，miR-145-5p、FSCN1 mRNA联合检测的AUC、灵敏度分别为0.947、92.3%，均显著高于单项指标的AUC、灵敏度（P < 0.05）。 结论 miR-145-5p、FSCN1与胃癌患者的临床病理特征有密切关系，是其生存预后有效预测指标。 -
关键词:
- 微小RNA-145-5p /
- 肌成束蛋白-1 /
- 胃癌 /
- 生存预测价值
Abstract:Objective To explore the expression and prognostic value of microRNA-145-5p （miR-145-5p） and fascin actin-bundling protein-1 （FSCN1） in gastric cancer tissues. Methods The study participants were selected from 103 gastric cancer patients treated at The First Hospital of Handan from August 2019 to August 2021. The expression levels of miR-145-5p and FSCN1 mRNA in the cancer tissues and adjacent non-cancerous tissues of gastric cancer patients were measured. Pearson correlation analysis was used to assess the relationship between the expression of miR-145-5p and FSCN1 mRNA. The area under curve （AUC） was used to evaluate the prognostic value of miR-145-5p and FSCN1 mRNA for gastric cancer patients. The Cox proportional hazards regression model was used to analyze factors influencing adverse prognosis, and Kaplan-Meier method was employed for survival analysis. Results The expression level of miR-145-5p was lower in cancer tissues compared to adjacent tissues （P < 0.05）, while the expression level of FSCN1 mRNA was higher in cancer tissues compared to adjacent tissues （P < 0.05）. The expression level of miR-145-5p was lower in cancer tissues of the patients with moderate-to-poor differentiation, tumor stage III+IV, invasion depth T3-T4, lymph node metastasis, or maximum tumor diameter ≥5 cm, compared to those with high differentiation, tumor stage I+II, invasion depth T1-T2, no lymph node metastasis, or maximum tumor diameter <5 cm, whereas the expression level of FSCN1 mRNA was higher （P < 0.05）. Pearson analysis revealed a negative correlation between miR-145-5p and FSCN1 mRNA expression in cancer tissues （r = -0.617, P = 0.000）. COX multivariate regression analysis indicated that moderate-to-poor differentiation, tumor stage III+IV, maximum tumor diameter≥5 cm, invasion depth T3-T4, low miR-145-5p expression, high FSCN1 mRNA expression, and lymph node metastasis were risk factors for poor prognosis in gastric cancer （P < 0.05）. Kaplan-Meier survival curves demonstrated a statistically significant difference in the 3-year overall survival rate between the low and high miR-145-5p expression groups （P < 0.05）. Similarly, a statistically significant difference was observed between the low and high FSCN1 mRNA expression groups （P < 0.05）. ROC curve analysis showed that the combined detection of miR-145-5p and FSCN1 mRNA yielded an AUC of 0.947 and a sensitivity of 92.3%, both of which were significantly higher than those of individual indicators （P < 0.05）. Conclusion MiR-145-5p and FSCN1 are closely related to the clinical pathological characteristics of gastric cancer patients and are effective prognostic indicators for survival. -
Key words:
- MicroRNA-145-5p /
- Fascin actin-bundling protein-1 /
- Gastric cancer /
- Prognostic value
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图 1 FSCN1 mRNA和miR-145-5p在不同组织中的表达情况[（$\bar x \pm s $），n = 103]
A：miR-145-5p表达情况；B：FSCN1 mRNA表达情况；*P < 0.05。
Figure 1. Expression of FSCN1 mRNA and miR-145-5p in different tissues [（$\bar x \pm s $），n = 103]
图 2 miR-145-5p高表达组和miR-145-5p低表达组3年总生存率
Figure 2. 3-year overall survival rate of miR-145-5p high expression group and miR-145-5p low expression group
图 3 FSCN1 mRNA高表达组和FSCN1 mRNA低表达组3年总生存率
Figure 3. 3-year overall survival rate of FSCN1 mRNA high expression group and FSCN1 mRNA low expression group
图 4 胃癌组织中miR-145-5p和FSCN1 mRNA表达预测患者死亡的ROC曲线
Figure 4. ROC curve of miR-145-5p and FSCN1 mRNA expression in gastric cancer tissue predicting patient mortality
表 1 引物序列
Table 1. Primer sequences
基因 正向引物 反向引物 引物长度（bp） miR-145-5 5'-GGTGCAGTGCTGCATCT-3' 5'-CTCAACTGGTGTCGTGGA-3' 17 内参U6 5'-GCTTCGGCAGCACATATACT-3' 5'-GTGCAGGGTCCGAGGTATTC-3' 20 FSCN1 mRNA 5'-CTGGCTACACGCTGGAGTTC-3' 5'-CTGAGTCCCCTGCTGTCTCC-3' 20 内参GAPDH 5'-GTCAACGGATTTGGTCTGTATT-3' 5'-AGTCTTCTGGGTGGCAGTGAT-3' 21 
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表 2 患者miR-145-5p、FSCN1 mRNA表达情况[（$\bar x \pm s $），n = 103]
Table 2. Expression of miR-145-5p and FSCN1 mRNA in patients [（$\bar x \pm s $），n = 103]
组别 miR-145-5p FSCN1 mRNA 癌组织 5.21±1.03 4.21±0.87 癌旁组织 9.13±1.84 2.35±0.56 t 18.867 18.245 P <0.001* <0.001* *P < 0.05。
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表 3 不同病理特征胃癌患者miR-145-5p、FSCN1 mRNA表达水平的比较[（$\bar x \pm s $），n = 103]
Table 3. Comparison of miR-145-5p and FSCN1 mRNA expression levels in gastric cancer patients with different pathological features [（$\bar x \pm s $），n = 103]
因素 n miR-145-5p t P FSCN1 mRNA t P 性别 0.239 0.811 0.222 0.825 男 60 5.23 ± 1.07 4.23 ± 0.91 女 43 5.18 ± 1.01 4.19 ± 0.89 年龄（岁） 0.144 0.886 ≥60 41 5.22 ± 1.04 4.20 ± 0.90 0.113 0.911 <60 62 5.19 ± 1.03 4.22 ± 0.87 Hp感染 0.234 0.816 0.174 0.862 有 72 5.19 ± 1.05 4.22 ± 0.87 无 31 5.24 ± 1.07 4.19 ± 0.85 肿瘤最大直径（cm） 2.287 0.024 2.811 0.006* ≥5 59 4.97 ± 1.01 4.47 ± 0.90 <5 44 5.44 ± 1.06 3.98 ± 0.84 分化程度（n） 2.621 0.010 2.815 0.006* 低中分化 65 5.09 ± 1.02 4.45 ± 0.83 高分化 38 5.42 ± 1.09 3.96 ± 0.89 TNM分期（n） 2.718 0.008 2.701 0.008* I+II 45 5.58 ± 1.05 4.01 ± 0.85 III+IV 58 5.01 ± 1.06 4.46 ± 083 淋巴结转移（n） 2.164 0.033 2.384 0.019* 有 49 5.05 ± 1.02 4.45 ± 0.84 无 54 5.36 ± 1.04 4.05 ± 0.86 T分期 2.205 0.029 2.606 0.011* T1～T2 48 5.49 ± 1.07 4.03 ± 0.87 T3～T4 55 5.02 ± 1.09 4.48 ± 0.88 *P < 0.05。
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表 4 COX回归分析赋值说明
Table 4. Explanation of COX regression analysis assignment
变量 赋值 肿瘤最大直径 <5 cm=0，≥5 cm=1 分化程度 高分化=0，低中分化=1 肿瘤分期 Ⅰ+Ⅱ=0，Ⅲ+Ⅳ=1 淋巴结转移 无=0，有=1 浸润深度 T1～T2=0，T3～T4=1 miR-145-5p 高表达=0，低表达=1 FSCN1 mRNA 低表达=0，高表达=1
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表 5 胃癌患者预后的多因素COX回归分析
Table 5. Multivariate Cox regression analysis of prognosis in gastric cancer patients
变量 单因素分析 多因素分析 HR 95%CI P HR 95%CI P 肿瘤最大直径 4.07 1.72～11.14 0.001 3.91 1.18～18.51 0.022* 分化程度 1.29 1.03～1.61 0.030 1.63 1.05～2.55 0.034* 肿瘤分期 1.87 1.26～2.85 0.003 1.93 1.55～2.41 <0.001 淋巴结转移 2.14 1.27～3.59 0.004 2.75 1.22～6.23 0.014* 浸润深度 1.93 1.22～3.08 0.007 1.84 1.25～2.72 0.003* miR-145-5p 2.12 1.11～4.05 0.024 2.68 1.81～3.98 <0.001 FSCN1 mRNA 3.56 1.56～8.06 0.002 3.678 1.630～8.304 0.002* *P < 0.05。
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表 6 胃癌组织中miR-145-5p和FSCN1 mRNA表达联合预测价值
Table 6. Joint predictive value of miR-145-5p and FSCN1 mRNA expression in gastric cancer tissue
指标 AUC 标准误 95%CI 特异度 灵敏度 miR-145-5p 0.797 0.043 0.712～0.884 80.1 72.4 FSCN1 mRNA 0.828 0.046 0.741～0.918 73.2 81.2 联合 0.947 0.021 0.905～0.987 65.6 92.3
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