Expression of COL6A2 and its clinical significance in gastric cancer

ZHENG Duoan1; ZHENG Manman2; MENG Xiangling3; SUN Dengqun1; SUN Yanjun1; CHEN Xiaoling4

PDF(2071 KB)

Medical Journal of the Chinese People Armed Police Forces ›› 2020, Vol. 31 ›› Issue (9) : 765-770.

Expression of COL6A2 and its clinical significance in gastric cancer

ZHENG Duoan¹, ZHENG Manman², MENG Xiangling³, SUN Dengqun¹, SUN Yanjun¹, CHEN Xiaoling⁴

Author information +

History +

Abstract

Objective To investigate the expression and clinical significance of type Ⅵ collagen alpha 2 chain (COL6A2) in gastric cancer, and to explore the possible underlying mechanisms. Methods Immunohistochemistry was used to detect the expressions of COL6A2 in sixty-two gastric cancer tissues and matched paracancerous tissues. The correlation between COL6A2 expressions and clinicopathological features was analyzed. The survival curve was plotted using the Kaplan-Meier method and validated by the Kaplan-Meier Plotter online database. Data about gastric cancer was downloaded from The Cancer Genome Atlas (TCGA) to analyze the correlation between COL6A2 and epithelial-mesenchymal transition-related protein expressions. Finally, Gene Set Enrichment Analysis (GSEA) was conducted to explore the possible mechanism of COL6A2 in gastric cancer. Results The positive expression rate of COL6A2 in gastric cancer tissues was significantly higher than in matched paracancerous tissues (43.5% vs. 25.8%, P=0.038). High expressions of COL6A2 were significantly correlated with lymph node metastasis, distant metastasis and TNM stage (P<0.05). Consistent with the result of Kaplan-Meier Plotter, survival analysis suggested that gastric cancer patients with high expressions of COL6A2 had a shorter survival time. Meanwhile, COL6A2 was an independent prognostic factor for gastric cancer (HR=2.339, 95% CI: 1.150-4.757, P=0.019). Correlation analysis revealed that COL6A2 expressions were closely related to the expressions of epithelial-mesenchymal transition-related proteins. GSEA showed that high expressions of COL6A2 samples were mainly enriched in several classical signaling pathways including TGF-beta signaling pathway and MAPK signaling pathway. Conclusions COL6A2 is highly expressed in gastric cancer tissues and is associated with poor prognosis. It could be a potential biomarker for the prognosis of gastric cancer patients.

Key words

gastric cancer / COL6A2 / immunohistochemistry / prognosis

Cite this article

EndNote

Ris (Procite)

Bibtex

Download Citations

ZHENG Duoan¹, ZHENG Manman², MENG Xiangling³, SUN Dengqun¹, SUN Yanjun¹, CHEN Xiaoling⁴. Expression of COL6A2 and its clinical significance in gastric cancer[J]. Medical Journal of the Chinese People Armed Police Forces. 2020, 31(9): 765-770

References

[1] Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2018, 68(6): 394-424.
[2] Siegel R L, Miller K D, Jemal A. Cancer statistics, 2018[J]. CA Cancer J Clin, 2018, 68(1): 7-30.
[3] Karimi P, Islami F, Anandasabapathy S, et al. Gastric cancer: descriptive epidemiology, risk factors, screening, and prevention[J]. Cancer Epidemiol Biomarkers Prev, 2014, 23(5): 700-713.
[4] Lamande S R, Bateman J F. Collagen Ⅵ disorders: Insights on form and function in the extracellular matrix and beyond[J]. Matrix Biol, 2018, 71-72: 348-367.
[5] Zhu H, Chen H, Wang J, et al. Collagen stiffness promoted non-muscle-invasive bladder cancer progression to muscle-invasive bladder cancer[J]. Onco Targets Ther, 2019, 12: 3441-3457.
[6] Haq F, Ahmed N, Qasim M. Comparative genomic analysis of collagen gene diversity[J]. Biotech, 2019, 9(3): 83.
[7] Cheon D J, Tong Y, Sim M S, et al. A collagen remodeling gene signature regulated by TGF-beta signaling is associated with metastasis and poor survival in serous ovarian cancer[J]. Clin Cancer Res, 2014, 20(3): 711-723.
[8] Peng J, Chen W, Chen J, et al. Overexpression of chloride channel-3 predicts unfavorable prognosis and promotes cellular invasion in gastric cancer[J]. Cancer Manag Res, 2018, 10: 1163-1175.
[9] Huang Z, Zhang N, Zha L, et al. Aberrant expression of the autocrine motility factor receptor correlates with poor prognosis and promotes metastasis in gastric carcinoma[J]. Asian Pac J Cancer Prev, 2014, 15(2): 989-997.
[10] Bushby K M, Collins J, Hicks D. Collagen type Ⅵ myopathies[J]. Adv Exp Med Biol, 2014, 802: 185-199.
[11] Jin Z, Yao J, Xie N, et al. Melittin constrains the expression of identified key genes associated with bladder cancer[J]. J Immunol Res, 2018, 2018: 5038172.
[12] Yang J, Hou Z, Wang C, et al. Gene expression profiles reveal key genes for early diagnosis and treatment of adamantinomatous craniopharyngioma[J]. Cancer Gene Ther, 2018, 25(9-10): 227-239.
[13] Hogan L E, Meyer J A, Yang J, et al. Integrated genomic analysis of relapsed childhood acute lymphoblastic leukemia reveals therapeutic strategies[J]. Blood, 2011, 118(19): 5218-5226.
[14] Chen Y C, Huang R L, Huang Y K, et al. Methylomics analysis identifies epigenetically silenced genes and implies an activation of beta-catenin signaling in cervical cancer[J]. Int J Cancer, 2014, 135(1): 117-127.
[15] Childs E J, Chaffee K G, Gallinger S, et al. Association of common susceptibility variants of pancreatic cancer in higher-risk patients: a pacgene study[J]. Cancer Epidemiol Biomarkers Prev, 2016, 25(7): 1185-1191.
[16] Chaffer C L, San Juan B P, Lim E, et al. EMT, cell plasticity and metastasis[J]. Cancer Metastasis Rev, 2016, 35(4): 645-654.
[17] Yang L, Qiu J, Xiao Y, et al. AP-2beta inhibits hepatocellular carcinoma invasion and metastasis through Slug and Snail to suppress epithelial-mesenchymal transition[J]. Theranostics, 2018, 8(13): 3707-3721.
[18] Zhu W, Cai M Y, Tong Z T, et al. Overexpression of EIF5A2 promotes colorectal carcinoma cell aggressiveness by upregulating MTA1 through C-myc to induce epithelial-mesenchymaltransition[J]. Gut, 2012, 61(4): 562-575.
[19] Massague J. TGFbeta in Cancer[J]. Cell, 2008, 134(2): 215-230.
[20] Saitoh M. Epithelial-mesenchymal transition is regulated at post-transcriptional levels by transforming growth factor-beta signaling during tumor progression[J]. Cancer Sci, 2015, 106(5): 481-488.
[21] Cantelli G, Crosas-Molist E, Georgouli M, et al. TGFBeta-induced transcription in cancer[J]. Semin Cancer Biol, 2017, 42: 60-69.
[22] Chen J, Ji T, Wu D, et al. Human mesenchymal stem cells promote tumor growth via MAPK pathway and metastasis by epithelial mesenchymal transition and integrin alpha5 in hepatocellular carcinoma[J]. Cell Death Dis, 2019, 10(6): 425.
[23] Park J, Scherer P E. Adipocyte-derived endotrophin promotes malignant tumor progression[J]. J Clin Invest, 2012, 122(11): 4243-4256.
[24] Voiles L, Lewis D E, Han L, et al. Overexpression of type Ⅵ collagen in neoplastic lung tissues[J]. Oncol Rep, 2014, 32(5): 1897-1904.