CD44 is a prognostic biomarker and correlated with immune infiltrates in gastric cancer

被引：41

作者：

Hou, Weiyan ^{[1
]}

Kong, Lingwei ^{[2
]}

Hou, Zhiping ^{[3
]}

Ji, Hairu ^{[3
]}

机构：

[1] Chengde Med Univ, Coll Basic Med, Chengde, Peoples R China

[2] Chengde Med Univ, Affiliated Hosp, Dept Orthopaed, Chengde, Peoples R China

[3] Chengde Med Univ, Dept Pathol, Shangerdaohezi Ave, Chengde 067000, Hebei, Peoples R China

来源：

BMC MEDICAL GENOMICS | 2022年 / 15卷 / 01期

关键词：

CD44; Gastric cancer; Prognosis; Immune infiltration; Bioinformatics; CELL MARKER CD44; STEM-CELL; EXPRESSION; IDENTIFICATION; MIGRATION; ROLES; NANOG;

D O I：

10.1186/s12920-022-01383-w

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Objective Gastric carcinoma is the most common malignant tumour of the human digestive system worldwide. CD44 serves as a marker for several tumour stem cells, including gastric cancer. However, the prognostic value of CD44 and its correlation with immune infiltration in gastric cancer remain unclear. Methods The relative expression level of CD44 RNA in gastric cancer was analysed in the TCGA and GEPIA2 databases and validated in the GEO database. Differences in CD44 between gastric cancer cell lines and normal cells were detected by real-time PCR, and the HPA database was used to analyse the differential expression of CD44 protein in gastric cancer and normal tissues. The effect of CD44 on the proliferation and migration of gastric cancer cells was detected by CCK8 and transwell assays. UALCAN was used to analyse the relationship between CD44 expression and clinical parameters, and the Kaplan-Meier Plotter was used to evaluate the prognostic value, including overall survival (OS), progression-free survival (PFS) and post-progression survival (PPS). The CD44 gene and protein interaction network was constructed by using the Linked Omics, GeneMANIA, STRING and DisGeNET databases. GO and KEGG analyses and GSEA of CD44 were performed by using R language. The correlation between CD44 and immune infiltration was explored by using the TIMER, CIBERSORT and GEPIA databases. Results CD44 is highly expressed in gastric cancer compared with normal tissues. Inhibition of proliferation and migration of gastric cancer cells after CD44 knockdown was observed. The UALCAN database showed that CD44 was independent of sex in gastric cancer but correlated with cancer stage and lymph node metastasis. Kaplan-Meier Plotter online analysis showed that OS, PFS and PPS were prolonged in the CD44 low-expression group. GO and KEGG analyses and GSEA results showed that CD44 was mainly located in the endoplasmic reticulum and the extracellular matrix containing collagen, which was mainly involved in protein digestion and absorption. TIMER, CIBERSORT and GEPIA showed that CD44 was associated with infiltrating immune cells and thereby affected survival prognosis. Conclusion CD44 is highly expressed in gastric cancer and is an independent prognostic factor associated with immune invasion, which can be used as a candidate prognostic biomarker to determine the prognosis associated with gastric immune invasion.

引用

页数：17

共 61 条

[1] Outcomes to first-line pembrolizumab in patients with non-small-cell lung cancer and very high PD-L1 expression [J].

Aguilar, E. J. ;

Ricciuti, B. ;

Gainor, J. F. ;

Kehl, K. L. ;

Kravets, S. ;

Dahlberg, S. ;

Nishino, M. ;

Sholl, L. M. ;

Adeni, A. ;

Subegdjo, S. ;

Khosrowjerdi, S. ;

Peterson, R. M. ;

Digumarthy, S. ;

Liu, C. ;

Sauter, J. ;

Rizvi, H. ;

Arbour, K. C. ;

Carter, B. W. ;

Heymach, J. V. ;

Altan, M. ;

Hellmann, M. D. ;

Awad, M. M. .

ANNALS OF ONCOLOGY, 2019, 30 (10) :1653-1659

[2] Characterization of the immunophenotypes and antigenomes of colorectal cancers reveals distinct tumor escape mechanisms and novel targets for immunotherapy [J].

Angelova, Mihaela ;

Charoentong, Pornpimol ;

Hackl, Hubert ;

Fischer, Maria L. ;

Snajder, Rene ;

Krogsdam, Anne M. ;

Waldner, Maximilian J. ;

Bindea, Gabriela ;

Mlecnik, Bernhard ;

Galon, Jerome ;

Trajanoski, Zlatko .

GENOME BIOLOGY, 2015, 16

[3] Specialized dendritic cells induce tumor-promoting IL-10+IL-17+ FoxP3neg regulatory CD4+ T cells in pancreatic carcinoma [J].

Barilla, Rocky M. ;

Diskin, Brian ;

Caso, Raul Caso ;

Lee, Ki Buom ;

Mohan, Navyatha ;

Buttar, Chandan ;

Adam, Salma ;

Sekendiz, Zennur ;

Wang, Junjie ;

Salas, Ruben D. ;

Cassini, Marcelo F. ;

Karlen, Jason ;

Sundberg, Belen ;

Akbar, Hashem ;

Levchenko, Dmitry ;

Gakhal, Inderdeep ;

Gutierrez, Johana ;

Wang, Wei ;

Hundeyin, Mautin ;

Torres-Hernandez, Alejandro ;

Leinwand, Joshua ;

Kurz, Emma ;

Rossi, Juan A. Kochen ;

Mishra, Ankita ;

Liria, Miguel ;

Sanchez, Gustavo ;

Panta, Jyoti ;

Loke, P'ng ;

Aykut, Berk ;

Miller, George .

NATURE COMMUNICATIONS, 2019, 10 (1)

[4] Cancer stem cell-immune cell crosstalk in tumour progression [J].

Bayik, Defne ;

Lathia, Justin D. .

NATURE REVIEWS CANCER, 2021, 21 (08) :526-536

[5] Unleashing Type-2 Dendritic Cells to Drive Protective Antitumor CD4+ T Cell Immunity [J].

Binnewies, Mikhail ;

Mujal, Adriana M. ;

Pollack, Joshua L. ;

Combes, Alexis J. ;

Hardison, Emily A. ;

Barry, Kevin C. ;

Tsui, Jessica ;

Ruhland, Megan K. ;

Kersten, Kelly ;

Abushawish, Marwan A. ;

Spasic, Marko ;

Giurintano, Jonathan P. ;

Chan, Vincent ;

Daud, Adil, I ;

Ha, Patrick ;

Ye, Chun J. ;

Roberts, Edward W. ;

Krummel, Matthew F. .

CELL, 2019, 177 (03) :556-+

[6] IFI16 promotes cervical cancer progression by upregulating PD-L1 in immunomicroenvironment through STING-TBK1-NF-kB pathway [J].

Cai, Hongning ;

Yan, Lin ;

Liu, Nian ;

Xu, Meng ;

Cai, Hongbing .

BIOMEDICINE & PHARMACOTHERAPY, 2020, 123

[7] Trimodality treatment in gastric and gastroesophageal junction cancers: Current approach and future perspectives [J].

Charalampakis, Nikolaos ;

Tsakatikas, Sergios ;

Schizas, Dimitrios ;

Kykalos, Stylianos ;

Tolia, Maria ;

Fioretzaki, Rodanthi ;

Papageorgiou, Georgios ;

Katsaros, Ioannis ;

Abdelhakeem, Ahmed Adel Fouad ;

Sewastjanow-Silva, Matheus ;

Rogers, Jane E. ;

Ajani, Jaffer A. .

WORLD JOURNAL OF GASTROINTESTINAL ONCOLOGY, 2022, 14 (01) :181-202

[8] The role of CD44 in pathological angiogenesis [J].

Chen, Li ;

Fu, Chenying ;

Zhang, Qing ;

He, Chengqi ;

Zhang, Feng ;

Wei, Quan .

FASEB JOURNAL, 2020, 34 (10) :13125-13139

[9] Identification and expansion of cancer stem cells in tumor tissues and peripheral blood derived from gastric adenocarcinoma patients [J].

Chen, Tie ;

Yang, Kun ;

Yu, Jianhua ;

Meng, Wentong ;

Yuan, Dandan ;

Bi, Feng ;

Liu, Fang ;

Liu, Jie ;

Dai, Bing ;

Chen, Xinzu ;

Wang, Fang ;

Zeng, Fan ;

Xu, Hong ;

Hu, Jiankun ;

Mo, Xianming .

CELL RESEARCH, 2012, 22 (01) :248-258

[10] De novo expression of CD44 variants in sporadic and hereditary gastric cancer [J].

da Cunha, Cristiana Branco ;

Oliveira, Carla ;

Wen, Xiaogang ;

Gomes, Barbara ;

Sousa, Sonia ;

Suriano, Gianpaolo ;

Grellier, Maritie ;

Huntsman, David G. ;

Carneiro, Fatima ;

Granja, Pedro L. ;

Seruca, Raquel .

LABORATORY INVESTIGATION, 2010, 90 (11) :1604-1614

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