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1.646000 四川 泸州,西南医科大学附属医院肿瘤科
2.402260 重庆,重庆市江津区中心医院肿瘤科
[孙贵银,E-mail:sunriseok@126.com SUN Guiyin, E-mail: sunriseok@126.com
收稿:2021-10-23,
修回:2021-12-17,
纸质出版:2022-03-30
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隆思睿, 向德兵, 申艺, 等. 细胞外基质蛋白1在结直肠癌中的表达和临床意义[J]. 陆军军医大学学报, 2022,44(6):549-555.
Sirui LONG, Debing XIANG, Yi SHEN, et al. Expression and clinical significance of extracellular matrix protein 1 in colorectal cancer[J]. Journal of Army Medical University, 2022, 44(6): 549-555.
隆思睿, 向德兵, 申艺, 等. 细胞外基质蛋白1在结直肠癌中的表达和临床意义[J]. 陆军军医大学学报, 2022,44(6):549-555. DOI: 10.16016/j.2097-0927.202110140.
Sirui LONG, Debing XIANG, Yi SHEN, et al. Expression and clinical significance of extracellular matrix protein 1 in colorectal cancer[J]. Journal of Army Medical University, 2022, 44(6): 549-555. DOI: 10.16016/j.2097-0927.202110140.
目的
2
探讨细胞外基质蛋白1(extracellular matrix protein 1
ECM1)在结直肠癌中的表达水平及其临床意义。
方法
2
收集肿瘤基因图谱(The Cancer Genome Atlas
TCGA
cancergenome.nih.gov/)、基因表达汇编(Gene Expression Omnibus
GEO,ncbi.nlm.nih.gov/geo/)数据库中结直肠癌组织及正常组织中的测序数据,分析ECM1在二者之间的表达差异及其与肿瘤的分期、预后的关系;收集重庆市江津区中心医院石蜡保存的标本及-80 ℃保存的新鲜结直肠癌组织,用免疫组化、RT-qPCR及Western blot检测ECM1在结直肠癌组织中的表达情况,χ
2
检验分析ECM1表达水平与患者临床病理特征之间的相关性,Kaplan-Meier分析ECM1的表达与结直肠癌患者预后之间的关系,Cox比例风险回归模型分析影响结直肠癌患者预后的临床指标。利用GSEA软件对TCGA数据库中结直肠癌
ECM
1基因进行富集分析,探究ECM1参与结直肠癌发生发展过程的可能调控通路。
结果
2
分析TCGA数据显示,在结直肠癌组织中,
ECM
1 mRNA的表达明显高于正常组织(
P
<
0.000 1),Ⅲ~Ⅳ期结直肠癌患者表达量明显高于Ⅰ~Ⅱ期患者(
P
<
0.05)。GEO数据库生存分析显示,ECM1高表达的患者预后较差(
P
<
0.01)。免疫组化、RT-qPCR及Western blot结果证实,ECM1在癌组织中的表达较癌旁正常组织上调(
P
<
0.001),其表达与患者淋巴结转移情况(
P
<
0.01)、TNM分期(
P
<
0.01)、神经侵犯(
P
<
0.05)和血清CEA水平(
P
<
0.01)密切相关。Kaplan-Meier生存分析显示,高表达ECM1的患者总生存时间明显缩短(
P
<
0.01),ECM1(
HR
=3.556
P
<
0.01)是结直肠癌患者预后的独立危险因素。ECM1高表达样本富集到细胞外基质受体相互作用、焦点粘连
、细胞黏附分子等相关基因集。
结论
2
ECM1在结直肠癌患者癌组织中高表达,与不良预后相关,并在结直肠癌的侵袭转移过程中发挥着重要的作用。
Objective
2
To investigate the expression level and clinical significance of extracellular matrix protein 1 (ECM1) in colorectal cancer.
Methods
2
The data from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database were used to compare the difference of ECM1 expression level in colorectal cancer tissues and adjacent tissues
and to explore the relationship of the level with tumor stage and prognosis. Paraffin preserved specimens and fresh specimens preserved at -80 ℃ and their corresponding clinical data were collected from Jiangjin District Central Hospital. The expression of ECM1 in these tissues was detected by immunohistochemical assay
RT-qPCR and Western blotting.
Chi
-square test was used to analyze the correlation of ECM1 level with patients' clinicopathological features. Kaplan-Meier survival analysis was adopted to analyze the relationship between the expression and prognosis. Cox proportional hazard regression analysis was employed to explore the indicators affecting the prognosis of the patients. ECM1 gene in colorectal cancer in TCGA database was enriched and analyzed by GSEA software to speculate the possible regulatory pathway of the gene involved in the occurrence and development of the cancer.
Results
2
Analysis on the data from TCGA database showed that ECM1 expression was higher in colorectal cancer tissues than adjacent normal tissues (
P
<
0.000 1)
and also higher in TNM stage Ⅲ~Ⅳ when compared with stage Ⅰ~Ⅱ colorectal cancer patients (
P
<
0.05). Survival analysis on the data from GEO database found that the patients with high ECM1 expression had poorer prognosis (
P
<
0.01). The Results of immunohistochemical
qPCR and Weste
rn blotting confirmed that the expression of ECM1 was up-regulated in the cancer tissues than the adjacent normal tissues
and its expression was closely associated with lymph node metastasis (
P
<
0.01)
TNM stage (
P
<
0.01)
nerve invasion (
P
<
0.05) and serum carcinoembryonic antigen (CEA) level (
P
<
0.01). Kaplan Meier survival analysis suggested that the overall survival of the patients with high ECM1 expression was significantly shortened (
P
<
0.01). Cox regression analysis indicated that ECM1 was an independent risk factor for the prognosis (
HR
=3.556
P
<
0.01) and should be used for predicting the prognosis of colorectal cancer. High expression of ECM1 was enriched into gene sets related to extracellular matrix receptor interaction
focal adhesion
cell adhesion molecules and so on.
Conclusion
2
ECM1 is highly expressed in colorectal cancer and associated with poor prognosis
and may play important role in the invasion and metastasis of the tumor.
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