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:
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.
Expression and clinical significance of extracellular matrix protein 1 in colorectal cancer
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.
关键词
Keywords
references
SUNG H, FERLAY J, SIEGEL R L, et al . Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J ] . CA Cancer J Clin, 2021, 71(3): 209-249. DOI: 10.3322/caac.21660.
YU Z J, TANG H Y, WEI M J. The progression of extracellular matrix protein-1 in malignant epithelial tumors[J]. Shanxi Med J, 2016, 45(10): 1168-1171. DOI: 10.3969/j.issn.0253-9926.2016.10.016.
JIA B, XIE T, QIU X L, et al . Long noncoding RNA FALEC inhibits proliferation and metastasis of tongue squamous cell carcinoma by epigenetically silencing ECM1 through EZH2[J ] . Aging, 2019, 11(14): 4990-5007. DOI: 10.18632/aging.102094.
YIN H J, WANG J S, LI H, et al . Extracellular matrix protein-1 secretory isoform promotes ovarian cancer through increasing alternative mRNA splicing and stemness[J ] . Nat Commun, 2021, 12(1): 1-19. DOI: 10.1038/s41467-021-24315-1.
WANG Z C, ZHOU Q, LI A L, et al . Extracellular matrix protein 1 (ECM1) is associated with carcinogenesis potential of human bladder cancer[J ] . Oncotargets Ther, 2019, 12: 1423-1432. DOI: 10.2147/ott.s191321.
JEONG S, LEE S G, KIM H, et al . Simultaneous expression of long non-coding RNA FAL1 and extracellular matrix protein 1 defines tumour behaviour in young patients with papillary thyroid cancer[J ] . Cancers, 2021, 13(13): 3223. DOI: 10.3390/cancers13133223.
CHEN H, JIA W, LI J. ECM1 promotes migration and invasion of hepatocellular carcinoma by inducing epithelial-mesenchymal transition[J]. World J Surg Oncol, 2016, 14(1): 195. DOI: 10.1186/s12957-016-0952-z.
LIU L Q, HU L, HU X B, et al . MiR-92a antagonized the facilitation effect of extracellular matrix protein 1 in GC metastasis through targeting its 3'UTR region[J ] . Food Chem Toxicol, 2019, 133: 110779. DOI: 10.1016/j.fct.2019.110779.
LAL G, HASHIMI S, SMITH B J, et al . Extracellular matrix 1 (ECM1) expression is a novel prognostic marker for poor long-term survival in breast cancer: a Hospital-based Cohort Study in Iowa[J ] . Ann Surg Oncol, 2009, 16(8): 2280-2287. DOI: 10.1245/s10434-009-0533-2.
STEINHAEUSER S S, MORERA E, BUDKOVA Z, et al . ECM1 secreted by HER2-overexpressing breast cancer cells promotes formation of a vascular niche accelerating cancer cell migration and invasion[J ] . Lab Investig, 2020, 100(7): 928-944. DOI: 10.1038/s41374-020-0415-6.
SHIN I. HER2 signaling in breast cancer[J]. Adv Exp Med Biol, 2021, 1187: 53-79. DOI: 10.1007/978-981-32-9620-6_3.
WU Q W, CHEN D H, LUO Q C, et al . Extracellular matrix protein 1 recruitsmoesin to facilitate invadopodia formation and breast cancer metastasis[J ] . Cancer Lett, 2018, 437: 44-55. DOI: 10.1016/j.canlet.2018.08.022.
GÓMEZ-CONTRERAS P, RAMIRO-DÍAZ J M, SIERRA A, et al . Extracellular matrix 1 (ECM1) regulates the actin cytoskeletal architecture of aggressive breast cancer cells in part via S100A4 and Rho-family GTPases[J ] . Clin Exp Metastas, 2017, 34(1): 37-49. DOI: 10.1007/s10585-016-9827-5.
LEE K M, NAM K, OH S, et al . ECM1 regulates tumor metastasis and CSC-like property through stabilization of β-catenin[J ] . Oncogene, 2015, 34(50): 6055-6065. DOI: 10.1038/onc.2015.54.
HOU Y Q, LOU J T, PENG L, et al . Detection and clinical significance of ECM1 gene expression in colorectal cancer tissue[J ] . World Chin J Dig, 2007, 15(17): 1960-1964. DOI: 10.3969/j.issn.1009-3079.2007.17.015.
HOU Y Q, ZHONG R Q, PENG L, et al . Expression and diagnostic value of ECM1 in colorectal cancer tissues[J ] . Shandong Med J, 2009, 49(52): 1-2. DOI: 10.3969/j.issn.1002-266X.2009.52.001.
URRA F A, FUENTES-RETAMAL S, PALOMINOS C, et al . Extracellular matrix signals as drivers of mitochondrial bioenergetics and metabolic plasticity of cancer cells during metastasis[J ] . Front Cell Dev Biol, 2021, 9: 751301. DOI: 10.3389/fcell.2021.751301.
SCHUMACHER S, VAZQUEZ NUNEZ R, BIERTVMPFEL C, et al . Bottom-up reconstitution of focal adhesion complexes[J ] . FEBS J, 2021. [Online ahead of print ] . DOI: 10.1111/febs.16023.
LI M, WANG Y, LI M W, et al . Integrins as attractive targets for cancer therapeutics[J ] . Acta Pharm Sin B, 2021, 11(9): 2726-2737. DOI: 10.1016/j.apsb.2021.01.004.
Proline-rich protein 11 is highly expressed in colorectal cancer to promote cancer cell invasion and metastasis
Relationships of iduronic acid-2-sulfatase with metastasis and prognosis of colorectal cancer
A novel estrogen receptor expression stratification (low/moderate/high) based on Chinese population provides more accurate prognosis prediction for HR+/HER2- early breast cancer patients
Immunosuppressive microenvironment of TGIF1-overexpressing gastric cancers and its clinical significance
Impact of molecular heterogeneity of NPM1 mutations on prognosis of acute myeloid leukemia: a clinical report of 86 cases
Related Author
Yao TANG
Jie WANG
Guiyin SUN
Zeyu YANG
Xiaoli HE
Tao TANG
Di WANG
Xuemei LIAO
Related Institution
Department of Oncology, Affiliated Hospital of Southwest Medical University
Institute of Pathology, Southwest Cancer Center, Army Medical University (Third Military Medical University)
Department of Stem Cell and Regenerative Medicine, First Affiliated Hospital, Army Medical University (Third Military Medical University)
Department of Breast and Thyroid Surgery, First Affiliated Hospital, Army Medical University (Third Military Medical University)
Chongqing Key Laboratory of Precision Prevention and Treatment for Digestive System Tumors, Department of Gastroenterology, Army Medical Center of PLA/Daping Hospital of Third Military Medical University