Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Oral Health
Published in: BMC Oral Health 1/2023

Open Access 01-12-2023 | Research

CERCAM is a prognostic biomarker associated with immune infiltration of macrophage M2 polarization in head and neck squamous carcinoma

Authors: Ying Yang, Cong Yan, Xiao-Jian Chen

Published in: BMC Oral Health | Issue 1/2023

Login to get access

Abstract

Purpose

This study aimed to investigate the relevance of cerebral endothelial cell adhesion molecule (CERCAM) expression to head and neck squamous cell carcinoma (HNSCC) prognosis and immune infiltration by macrophage M2 polarization.

Methods

Timer, UALCAN and HPA databases was used to analyze the differences in mRNA and protein levels of CERCAM expression in HNSCC. The Timer database was also applied to analyze the correlation between CERCAM in HNSCC and immune infiltration. TCGA-HNSCC database was applied to analyze the correlation between CERCAM expression levels and clinicopathological features, and its diagnostic and prognostic value in HNSCC was also assessed. The cBioPortal and MethSurv databases were then applied to analyze the genetic variation and methylation status of CERCAM. In vitro cellular assays were performed to provide evidence that CERCAM promotes malignant biological behavior of tumors and promotes macrophage M2 polarization in tumors. Finally, underlying pathophysiological mechanisms of CERCAM involvement in the development of HNSCC were predicted using a bioinformatics approach.

Results

CERCAM is significantly overexpressed in HNSCC and correlates with poor prognostic levels and has good performance in predicting survival status in HNSCC patients. Cox regression analysis indicates that CERCAM expression levels are independent risk factors for predicting OS, DSS, and PFI. CERCAM promotes tumor malignant biological behavior and promotes macrophage M2 polarization immune infiltration in HNSCC. In addition, CERCAM promotes tumor cell adhesion in head and neck squamous carcinoma and promotes tumor progression through several oncogenic signaling pathways.

Conclusion

CERCAM may serve as a new diagnostic and prognostic biomarker in HNSCC and is a promising therapeutic target for HNSCC.
Appendix
Available only for authorised users
Literature
1.
Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022;72(1):7–33.CrossRefPubMed
2.
de Bree R, Leemans CR. Recent advances in surgery for head and neck cancer. Curr Opin Oncol. 2010;22(3):186–93.PubMed
3.
Alterio D, Marvaso G, Ferrari A, Volpe S, Orecchia R, Jereczek-Fossa BA. Modern radiotherapy for head and neck cancer. Semin Oncol. 2019;46(3):233–45.PubMed
4.
Rajendra A, Noronha V, Joshi A, Patil VM, Menon N, Prabhash K. Palliative chemotherapy in head and neck cancer: balancing between beneficial and adverse effects. Expert Rev Anticancer Ther. 2020;20(1):17–29.PubMed
5.
Cramer JD, Burtness B, Ferris RL. Immunotherapy for head and neck cancer: recent advances and future directions. Oral Oncol. 2019;99:104460.PubMedPubMedCentral
6.
Ling Z, Cheng B, Tao X. Epithelial-to-mesenchymal transition in oral squamous cell carcinoma: challenges and opportunities. Int J Cancer. 2021;148(7):1548–61.PubMed
7.
Gavrielatou N, Doumas S, Economopoulou P, Foukas PG, Psyrri A. Biomarkers for immunotherapy response in head and neck cancer. Cancer Treat Rev. 2020;84:101977.PubMed
8.
Arantes L, De Carvalho AC, Melendez ME, Lopes CA. Serum, plasma and saliva biomarkers for head and neck cancer. Expert Rev Mol Diagn. 2018;18(1):85–112.PubMed
9.
10.
Berrier AL, Yamada KM. Cell-matrix adhesion. J Cell Physiol. 2007;213(3):565–73.PubMed
11.
Monemian Esfahani A, Rosenbohm J, Reddy K, Jin X, Bouzid T, Riehl B, et al. Tissue Regeneration from Mechanical Stretching of Cell-Cell Adhesion. Tissue Eng Part C Methods. 2019;25(11):631–40.PubMedPubMedCentral
12.
Elangbam CS, Qualls CW Jr, Dahlgren RR. Cell adhesion molecules–update. Vet Pathol. 1997;34(1):61–73.PubMed
13.
Opiłka MN, Lorenc Z, Starzewska M, Lorenc J, Rajs A. Cell adhesion molecules in terms of carcinogenesis. Pol Przegl Chir. 2014;86(3):151–7.PubMed
14.
Laffón A, González-Amaro R. Cell adhesion molecules: an overview. Br J Rheumatol. 1995;34(12):1101–2.PubMed
15.
Beauchemin N, Arabzadeh A. Carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) in cancer progression and metastasis. Cancer Metastasis Rev. 2013;32(3–4):643–71.PubMed
16.
Luís C, Soares R, Fernandes R, Botelho M. Cell-adhesion Molecules as Key Mechanisms of Tumor Invasion: The Case of Breast Cancer. Curr Mol Med. 2023;23(2):147–60.PubMed
17.
Mason MD, Davies G, Jiang WG. Cell adhesion molecules and adhesion abnormalities in prostate cancer. Crit Rev Oncol Hematol. 2002;41(1):11–28.PubMed
18.
Ismail AA, Mahboob T, Samudi Raju C, Sekaran SD. Zika virus modulates blood-brain barrier of brain microvascular endothelial cells. Trop Biomed. 2019;36(4):888–97.PubMed
19.
Xu T, Xu W, Zheng Y, Li X, Cai H, Xu Z, et al. Comprehensive FGFR3 alteration-related transcriptomic characterization is involved in immune infiltration and correlated with prognosis and immunotherapy response of bladder cancer. Front Immunol. 2022;13:931906.PubMedPubMedCentral
20.
Nie S, Huili Y, He Y, Hu J, Kang S, Cao F. Identification of bladder cancer subtypes based on necroptosis-related genes, construction of a prognostic model. Frontiers in surgery. 2022;9:860857.PubMedPubMedCentral
21.
Zuo Y, Xu X, Chen M, Qi L. The oncogenic role of the cerebral endothelial cell adhesion molecule (CERCAM) in bladder cancer cells in vitro and in vivo. Cancer Med. 2021;10(13):4437–50.PubMedPubMedCentral
22.
Jarosz-Biej M, Smolarczyk R, Cichoń T, Kułach N. Tumor Microenvironment as a “Game Changer” in cancer radiotherapy. Int J Mol Sci. 2019;20(13):3212.PubMedPubMedCentral
23.
Hinshaw DC, Shevde LA. The tumor microenvironment innately modulates cancer progression. Cancer Res. 2019;79(18):4557–66.PubMedPubMedCentral
24.
Li C, Teixeira AF, Zhu HJ, Ten Dijke P. Cancer associated-fibroblast-derived exosomes in cancer progression. Mol Cancer. 2021;20(1):154.PubMedPubMedCentral
25.
Achyut BR, Shankar A, Iskander AS, Ara R, Angara K, Zeng P, et al. Bone marrow derived myeloid cells orchestrate antiangiogenic resistance in glioblastoma through coordinated molecular networks. Cancer Lett. 2015;369(2):416–26.PubMedPubMedCentral
26.
Jiang Y, Zhan H. Communication between EMT and PD-L1 signaling: New insights into tumor immune evasion. Cancer Lett. 2020;468:72–81.PubMed
27.
Huang J, Zhang L, Wan D, Zhou L, Zheng S, Lin S, et al. Extracellular matrix and its therapeutic potential for cancer treatment. Signal Transduct Target Ther. 2021;6(1):153.PubMedPubMedCentral
28.
Ngambenjawong C, Gustafson HH, Pun SH. Progress in tumor-associated macrophage (TAM)-targeted therapeutics. Adv Drug Deliv Rev. 2017;114:206–21.PubMedPubMedCentral
29.
Lopez-Yrigoyen M, Cassetta L, Pollard JW. Macrophage targeting in cancer. Ann N Y Acad Sci. 2021;1499(1):18–41.PubMed
30.
Locati M, Curtale G, Mantovani A. Diversity, Mechanisms, and Significance of Macrophage Plasticity. Annu Rev Pathol. 2020;15:123–47.PubMed
31.
32.
Chen Y, Zhang S, Wang Q, Zhang X. Tumor-recruited M2 macrophages promote gastric and breast cancer metastasis via M2 macrophage-secreted CHI3L1 protein. J Hematol Oncol. 2017;10(1):36.PubMedPubMedCentral
33.
Mu X, Shi W, Xu Y, Xu C, Zhao T, Geng B, et al. Tumor-derived lactate induces M2 macrophage polarization via the activation of the ERK/STAT3 signaling pathway in breast cancer. Cell cycle (Georgetown, Tex). 2018;17(4):428–38.PubMedPubMedCentral
34.
Li T, Fu J, Zeng Z, Cohen D, Li J, Chen Q, et al. TIMER2.0 for analysis of tumor-infiltrating immune cells. Nucleic acids Res. 2020;48(W1):W509-w14.PubMedPubMedCentral
35.
Chandrashekar DS, Bashel B, Balasubramanya SAH, Creighton CJ, Ponce-Rodriguez I, Chakravarthi B, et al. UALCAN: A Portal for Facilitating Tumor Subgroup Gene Expression and Survival Analyses. Neoplasia (New York, NY). 2017;19(8):649–58.
36.
Tomczak K, Czerwińska P, Wiznerowicz M. The Cancer Genome Atlas (TCGA): an immeasurable source of knowledge. Contemp Oncol (Poznan, Poland). 2015;19(1a):A68-77.
37.
Gao J, Aksoy BA, Dogrusoz U, Dresdner G, Gross B, Sumer SO, et al. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal. 2013;6(269):pl1.PubMedPubMedCentral
38.
Modhukur V, Iljasenko T, Metsalu T, Lokk K, Laisk-Podar T, Vilo J. MethSurv: a web tool to perform multivariable survival analysis using DNA methylation data. Epigenomics. 2018;10(3):277–88.PubMed
39.
Han Y, Wang Y, Dong X, Sun D, Liu Z, Yue J, et al. TISCH2: expanded datasets and new tools for single-cell transcriptome analyses of the tumor microenvironment. Nucleic Acids Res. 2023;51(D1):D1425–31.PubMed
40.
Vasaikar SV, Straub P, Wang J, Zhang B. LinkedOmics: analyzing multi-omics data within and across 32 cancer types. Nucleic Acids Res. 2018;46(D1):D956–63.PubMed
41.
42.
43.
Kanehisa M, Furumichi M, Sato Y, Kawashima M, Ishiguro-Watanabe M. KEGG for taxonomy-based analysis of pathways and genomes. Nucleic Acids Res. 2023;51:D587–92.PubMed
44.
Miricescu D, Totan A, Stanescu S II, Badoiu SC, Stefani C, Greabu M. PI3K/AKT/mTOR signaling pathway in breast cancer: from molecular landscape to clinical aspects. Int J Mol Sci. 2020;22(1):173.PubMedPubMedCentral
45.
Fresno Vara JA, Casado E, de Castro J, Cejas P, Belda-Iniesta C, González-Barón M. PI3K/Akt signalling pathway and cancer. Cancer Treat Rev. 2004;30(2):193–204.PubMed
46.
Drosten M, Barbacid M. Targeting the MAPK pathway in KRAS-driven tumors. Cancer Cell. 2020;37(4):543–50.PubMed
47.
48.
Szturz P, Vermorken JB. Overcoming frailty in recurrent and metastatic head and neck cancer. Oral Oncol. 2020;109:104636.PubMed
49.
Ota I, Kitahara T. Cancer of unknown primary in the head and neck: Diagnosis and treatment. Auris Nasus Larynx. 2021;48(1):23–31.PubMed
50.
Roldán FL, Izquierdo L, Ingelmo-Torres M, Lozano JJ, Carrasco R, Cuñado A, et al. Prognostic gene expression-based signature in clear-cell renal cell carcinoma. Cancers (Basel). 2022;14(15):3754.PubMed
51.
Gerovska D, Garcia-Gallastegi P, Crende O, Márquez J, Larrinaga G, Unzurrunzaga M, et al. GeromiRs are downregulated in the tumor microenvironment during colon cancer colonization of the liver in a murine metastasis model. Int J Mol Sci. 2021;22(9):4819.PubMedPubMedCentral
52.
Boutilier AJ, Elsawa SF. Macrophage polarization states in the tumor microenvironment. Int J Mol Sci. 2021;22(13):6995.PubMedPubMedCentral
53.
Wu K, Lin K, Li X, Yuan X, Xu P, Ni P, et al. Redefining tumor-associated macrophage subpopulations and functions in the tumor microenvironment. Front Immunol. 2020;11:1731.PubMedPubMedCentral
Metadata
Title
CERCAM is a prognostic biomarker associated with immune infiltration of macrophage M2 polarization in head and neck squamous carcinoma
Authors
Ying Yang
Cong Yan
Xiao-Jian Chen
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Oral Health / Issue 1/2023
Electronic ISSN: 1472-6831
DOI
https://doi.org/10.1186/s12903-023-03421-0

Other articles of this Issue 1/2023

BMC Oral Health 1/2023 Go to the issue

Research

Evaluation of dental pulp stem cells behavior after odontogenic differentiation induction by three different bioactive materials on two different scaffolds

Research

Synthesis and characterization of hydroxyapatite nanoparticles and their effects on remineralization of demineralized enamel in the presence of Er,Cr: YSGG laser irradiation

Research

Modified interproximal tunneling technique with customized sub-epithelial connective tissue graft for gingival papilla reconstruction: report of three cases with a cutback incision on the palatal side

Correction

Correction: Evaluation of different models of intrusive force application and temporary anchorage device (TAD) placement in total arch intrusion using clear aligners; a finite element analysis

Research

Dental caries status and its associated factors among schoolchildren aged 6–8 years in Hangzhou, China: a cross-sectional study

Case report

Orthodontic treatment of traumatically avulsed maxillary central incisors with bimaxillary dentoalveolar protrusion in an adult female: a case report