This study aimed to examine the expression and clinical significance of chemokine-like factor-like MARVEL transmembrane domain-containing family member 8 (CMTM8) in gastric cancer (GC). The mRNA and protein expression of CMTM8 were detected by bioinformatics analysis and immunohistochemistry (IHC), respectively. Bioinformatics analysis found that there was a high mRNA expression of CMTM8 in GC tissues, but failed to identify a significant relationship with the clinicopathological features or prognosis of GC patients. However, IHC results showed that the positive expression of CMTM8 protein in GC tissues was significantly lower than that of adjacent nontumor tissues and correlated with differentiation, tumor node metastasis stage, and distal metastasis of GC patients (p < 0.05). Moreover, the survival time of GC patients with negative CMTM8 protein expression group was shorter than that of positive CMTM8 protein expression group by Kaplan–Meier survival analysis (p < 0.05). Cox proportional hazards model (COX) regression analysis indicated that CMTM8 protein was an independent protective factor for the overall survival of GC patients. Further Gene Set Enrichment Analysis suggested that CMTM8 may be involved in regulating the calcium signaling pathway, cell adhesion molecules, and cytokine–cytokine receptor interaction in GC. Our study shows that CMTM8 protein is downregulated in GC tissues, and CMTM8 protein expression is related to GC metastasis and the prognosis of GC patients.
Get full access to this article
View all access options for this article.
References
1.
BeiC., TanC., ZhuX., WangZ., and TanS. (2018). Association between polymorphisms in CMTM family genes and hepatocellular carcinoma in Guangxi of China. DNA Cell Biol, 37, 691–696.
2.
BothJ., KrijgsmanO., BrasJ., SchaapG.R., BaasF., YlstraB., et al. (2014). Focal chromosomal copy number aberrations identify CMTM8 and GPR177 as new candidate driver genes in osteosarcoma. PLoS One 9,e115835.
3.
BrayF., FerlayJ., SoerjomataramI., SiegelR.L., TorreL.A., and JemalA. (2018). Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 68, 394–424.
4.
CaiX., DengJ., MingQ., CaiH., and ChenZ. (2020). Chemokine-like factor 1: a promising therapeutic target in human diseases. Exp Biol Med (Maywood), 245, 1518–1528.
5.
ChenS., DuY., HuangY., WangX., GuQ., and DongZ. (2007). Effects of novel human chemokine-like factor superfamily 8 on proliferation and EGFR expression of HL-60 cells. J Exp Hematol 15,458.
6.
ChenW., XiaC., ZhengR., ZhouM., LinC., ZengH., et al. (2019). Disparities by province, age, and sex in site-specific cancer burden attributable to 23 potentially modifiable risk factors in China: a comparative risk assessment. Lancet Glob Health, 7, e257–e269.
7.
ChoiY.K., WooS.M., ChoS.G., MoonH.E., YunY.J., KimJ.W., et al. (2013). Brain-metastatic triple-negative breast cancer cells regain growth ability by altering gene expression patterns. Cancer Genom Proteom, 10, 265–275.
8.
DonningerH., BonomeT., RadonovichM., Pise-MasisonC.A., BradyJ., ShihJ.H., et al. (2004). Whole genome expression profiling of advance stage papillary serous ovarian cancer reveals activated pathways. Oncogene, 23, 8065–8077.
9.
DuanH.J., LiX.Y., LiuC., and DengX.L. (2020). Chemokine-like factor-like MARVEL transmembrane domain-containing family in autoimmune diseases. Chin Med J (Engl), 133, 951–958.
10.
GaoD., HuH., WangY., YuW., ZhouJ., WangX., et al. (2015). CMTM8 inhibits the carcinogenesis and progression of bladder cancer. Oncol Rep, 34, 2853–2863.
11.
GohL.Y., LeowA.H., and GohK.L. (2014). Observations on the epidemiology of gastrointestinal and liver cancers in the Asia-Pacific region. J Dig Dis, 15, 463–468.
12.
GuoX., ZhangS., TanS., BeiC., ZhangH., ZhuX., et al. (2020). Downregulated CMTM2 poses potential clinical significance in hepatocellular carcinoma. DNA Cell Biol, 39, 683–689.
13.
HanW., DingP., XuM., WangL., RuiM., ShiS., et al. (2003). Identification of eight genes encoding chemokine-like factor superfamily members 1–8 (CKLFSF1-8) by in silico cloning and experimental validation. Genomics, 81, 609–617.
14.
HanW., LouY., TangJ., ZhangY., ChenY., LiY., et al. (2001). Molecular cloning and characterization of chemokine-like factor 1 (CKLF1), a novel human cytokine with unique structure and potential chemotactic activity. Biochem J, 357, 127–135.
15.
HuH., ChenJ.W., XuK.X., WangD., WangY., WangG.W., et al. (2013). [Expressions of CMTM8 and E-cadherin in primary and metastatic clear cell renal cell carcinoma]. Beijing Da Xue Xue Bao Yi Xue Ban, 45, 537–541.
16.
HuangY., LiF., and DuY. (2006). Effects of CKLFSF8 on expression of EGFR of BGC823 cell. J Zhengzhou Univ (Med Sci), 41, 617–619.
17.
HuangZ.M., LiP.L., YangP., HouX.D., YangY.L., XuX., et al. (2019). Overexpression of CMTM7 inhibits cell growth and migration in liver cancer. Kaohsiung J Med Sci, 35, 332–340.
18.
JinC., DingP., WangY., and MaD. (2005). Regulation of EGF receptor signaling by the MARVEL domain-containing protein CKLFSF8. FEBS Lett, 579, 6375–6382.
19.
JinC., WangY., HanW., ZhangY., HeQ., LiD., et al. (2007). CMTM8 induces caspase-dependent and -independent apoptosis through a mitochondria-mediated pathway. J Cell Physiol, 211, 112–120.
20.
KongL.L., WangZ.Y., HanN., ZhuangX.M., WangZ.Z., LiH., et al. (2014). Neutralization of chemokine-like factor 1, a novel C-C chemokine, protects against focal cerebral ischemia by inhibiting neutrophil infiltration via MAPK pathways in rats. J Neuroinflammation 11,112.
21.
LiD., JinC., YinC., ZhangY., PangB., TianL., et al. (2007). An alternative splice form of CMTM8 induces apoptosis. Int J Biochem Cell Biol, 39, 2107–2119.
22.
LiM., LuoF., TianX., YinS., ZhouL., and ZhengS. (2020). Chemokine-like factor-like MARVEL transmembrane domain-containing family in hepatocellular carcinoma: latest advances. Front Oncol 10,595973.
23.
MezzadraR., SunC., JaeL.T., Gomez-EerlandR., de VriesE., WuW., et al. (2017). Identification of CMTM6 and CMTM4 as PD-L1 protein regulators. Nature, 549, 106–110.
24.
ShiW., ZhangC., NingZ., HuaY., LiY., ChenL., et al. (2021). CMTM8 as an LPA1-associated partner mediates lysophosphatidic acid-induced pancreatic cancer metastasis. Ann Transl Med 9,42.
25.
SuY., LinY., ZhangL., LiuB., YuanW., MoX., et al. (2014). CMTM3 inhibits cell migration and invasion and correlates with favorable prognosis in gastric cancer. Cancer Sci, 105, 26–34.
26.
WangJ., ZhangG., ZhangY., LuoY., SongQ., QiuX., et al. (2014). CMTM1_v17 is a novel potential therapeutic target in breast cancer. Oncol Rep, 32, 1829–1836.
27.
ZhangS., PeiX., HuH., ZhangW., MoX., SongQ., et al. (2016). Functional characterization of the tumor suppressor CMTM8 and its association with prognosis in bladder cancer. Tumour Biol, 37, 6217–6225.
28.
ZhangW., MendozaM.C., PeiX., IlterD., MahoneyS.J., ZhangY., et al. (2012). Down-regulation of CMTM8 induces epithelial-to-mesenchymal transition-like changes via c-MET/extracellular signal-regulated kinase (ERK) signaling. J Biol Chem, 287, 11850–11858.
29.
ZhangW., QiH., MoX., SunQ., LiT., SongQ., et al. (2017). CMTM8 is frequently downregulated in multiple solid tumors. Appl Immunohistochem Mol Morphol, 25, 122–128.
30.
ZhuX., QiG., LiC., BeiC., TanC., ZhangY., et al. (2019). Expression and clinical significance of CMTM6 in hepatocellular carcinoma. DNA Cell Biol, 38, 193–197.
