Integrative profiling of CEACAM1 in different malignancies with implications on the SARS-CoV-2 infection genes ACE2 and TMPRSS2

Year 2023, Volume: 51 Issue: 2, 215 - 225, 01.04.2023

Ahmet Acar

https://doi.org/10.15671/hjbc.1232843

Cited By: 1

Abstract

Increasing number of evidence demonstrated increased SARS-CoV-2 infection risk in cancer. Despite various studies shed light on SARS-CoV-2 mediated pathways upregulated in cancer, there is still ongoing efforts to reveal underlying mechanisms of elevated risk for COVID-19 disease in cancer. Given critical role of CEACAM1 in immune exhaustion and immune deregulation observed both in cancer and COVID-19, systematic characterization of CEACAM1 in different malignancies was performed with an ultimate aim to identify the involvement of CEACAM1 in enhanced COVID-19 susceptibility in cancer patients. Here we show that CEACAM1 expression was upregulated in a number of TCGA samples. In addition, CEACAM1 expression was positively correlated with SARS-CoV-2 infection genes in TCGA samples. Single-cell RNA sequencing analysis results of COVID-19 positive patients indicated upregulation of CEACAM1 expression. Furthermore, CEACAM1 expression was associated with HAVCR2, an immune checkpoint marker, and there was a correlation between CEACAM1 and HAVCR2 levels in different TCGA samples. Collectively, CEACAM1 might provide increased susceptibility of COVID-19 disease in cancer patients which might be explained with its interaction with HAVCR2.

Keywords

SARS-CoV-2, COVID-19, CEACAM1, Cancer

Supporting Institution

TUBITAK

Project Number

118C197

References

• G. Pascarella, A. Strumia, C. Piliego, F. Bruno, R. del Buono, F. Costa, S. Scarlata, and F. E. Agrò, COVID-19 diagnosis and management: a comprehensive review, J Intern Med, 288 (2020) 192-206.
• A. C. Walls, Y. J. Park, M. A. Tortorici, A. Wall, A. T. McGuire, and D. Veesler, Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein, Cell, 181 (2020) 281-292.
• A. G. Harrison, T. Lin, and P. Wang, Mechanisms of SARS-CoV-2 Transmission and Pathogenesis, Trends Immunol, 41 (2020) 1472-1479.
• Y. H. Shin, K. Jeong, J. Lee, H. J. Lee, J. Yim, J. Kim, S. Kim, and S. B. Park, Inhibition of ACE2-Spike Interaction by an ACE2 Binder Suppresses SARS-CoV-2 Entry, Angewandte Chemie - International Edition, 61 (2022) 110-1115.
• R. Zang, M. F. G. Castro, B. T. McCune, Q. Zeng, P. W. Rothlauf, N. M. Sonnek, Z. Liu, K. F. Brulois, X. Wang, H. B. Greenberg, M. S. Diamond, M. A. Ciorba, S. P. J. Whelan, and S. Ding, TMPRSS2 and TMPRSS4 promote SARS-CoV-2 infection of human small intestinal enterocytes, Sci Immunol, 5 (2020) 20221-20226.
• H. Yao, Y. Song, Y. Chen, N. Wu, J. Xu, C. Sun, J. Zhang, T. Weng, Z. Zhang, Z. Wu, L. Cheng, D. Shi, X. Lu, J. Lei, M. Crispin, Y. Shi, L. Li, and S. Li, Molecular Architecture of the SARS-CoV-2 Virus, Cell, 183 (2020) 730-738.
• C. Turnquist, B. M. Ryan, I. Horikawa, B. T. Harris, and C. C. Harris, Cytokine Storms in Cancer and COVID-19, Cancer Cell, 38 (2020) 598-601.
• F. Yang, S. Shi, J. Zhu, J. Shi, K. Dai, and X. Chen, Clinical characteristics and outcomes of cancer patients with COVID-19, J Med Virol, 92 (2020) 2067-2073.
• M. H. Antikchi, H. Neamatzadeh, Y. Ghelmani, J. Jafari-Nedooshan, S. A. Dastgheib, S. Kargar, M. Noorishadkam, R. Bahrami, and M. H. Jarahzadeh, The Risk and Prevalence of COVID-19 Infection in Colorectal Cancer Patients: a Systematic Review and Meta-analysis, J Gastrointest Cancer, 52 (2021) 73-79.
• M. Aznab, Evaluation of COVID 19 infection in 279 cancer patients treated during a 90-day period in 2020 pandemic, Int J Clin Oncol, 25 (2020) 1581-1586.
• J. Y. Y. Kwan, L. T. Lin, R. Bell, J. P. Bruce, C. Richardson, T. J. Pugh, and F. F. Liu, Elevation in viral entry genes and innate immunity compromise underlying increased infectivity and severity of COVID-19 in cancer patients, Sci Rep, 11 (2021) 4533.
• S. F. Pedersen and Y. C. Ho, SARS-CoV-2: A storm is raging, Journal of Clinical Investigation, 130 (2020) 2022-2025.
• C. Qin, L. Zhou, Z. Hu, S. Zhang, S. Yang, Y. Tao, C. Xie, K. Ma, K. Shang, W. Wang, and D.-S. Tian, Dysregulation of Immune Response in Patients with COVID-19 in Wuhan, China, SSRN Electronic Journal, (2020) 762-768.
• C. Huang, Y. Wang, X. Li, L. Ren, J. Zhao, Y. Hu, L. Zhang, G. Fan, J. Xu, X. Gu, Z. Cheng, T. Yu, J. Xia, Y. Wei, W. Wu, X. Xie, W. Yin, H. Li, M. Liu, Y. Xiao, H. Gao, L. Guo, J. Xie, G. Wang, R. Jiang, Z. Gao, Q. Jin, J. Wang, and B. Cao, Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China, The Lancet, 395 (2020) 497-506.
• M. B. LATIF, S. SHUKLA, P. M. del RIO ESTRADA, S. P. RIBEIRO, R. P. SEKALY, and A. A. SHARMA, Immune mechanisms in cancer patients that lead to poor outcomes of SARS-CoV-2 infection, Translational Research, 241 (2022) 83-95.
• Y. Meng, J. Sun, G. Zhang, T. Yu, and H. Piao, A Pan-Cancer In Silico Analysis of the COVID-19 Internalization Protease: Transmembrane Proteaseserine-2, Front Genet, 13 (2022) 18991-18999.
• H. Li, L. Xie, L. Chen, L. Zhang, Y. Han, Z. Yan, and X. Guo, Genomic, epigenomic, and immune subtype analysis of CTSL/B and SARS-CoV-2 receptor ACE2 in pan-cancer, Aging, 12 (2020) 22370-22389.
• P. Katopodis, V. Anikin, H. S. Randeva, D. A. Spandidos, K. Chatha, I. Kyrou, and E. Karteris, Pan-cancer analysis of transmembrane protease serine 2 and cathepsin L that mediate cellular SARS.CoV.2 infection leading to COVID-19, Int J Oncol, 57 (2020) 533-539.
• M. A. Temena and A. Acar, Increased TRIM31 gene expression is positively correlated with SARS-CoV-2 associated genes TMPRSS2 and TMPRSS4 in gastrointestinal cancers, Sci Rep, 12 (2022) 11763.
• Y.-J. Dai, F. Hu, H. Li, H.-Y. Huang, D.-W. Wang, and Y. Liang, A profiling analysis on the receptor ACE2 expression reveals the potential risk of different type of cancers vulnerable to SARS-CoV-2 infection, Ann Transl Med, 8 (2020) 481.
• M. Rumpret, J. Drylewicz, L. J. E. Ackermans, J. A. M. Borghans, R. Medzhitov, and L. Meyaard, Functional categories of immune inhibitory receptors, Nat Rev Immunol, 20 (2020) 771-780.
• M. B. Abid, M. Mughal, and M. A. Abid, Coronavirus Disease 2019 (COVID-19) and Immune-Engaging Cancer Treatment, JAMA Oncol, 6 (2020) 1529.
• S. Vivarelli, L. Falzone, F. Torino, G. Scandurra, G. Russo, R. Bordonaro, F. Pappalardo, D. A. Spandidos, G. Raciti, and M. Libra, Immune-checkpoint inhibitors from cancer to COVID-19: A promising avenue for the treatment of patients with COVID-19 (Review), Int J Oncol, 58 (2021) 145-157.
• Y.-H. Huang, C. Zhu, Y. Kondo, A. C. Anderson, A. Gandhi, A. Russell, S. K. Dougan, B.-S. Petersen, E. Melum, T. Pertel, K. L. Clayton, M. Raab, Q. Chen, N. Beauchemin, P. J. Yazaki, M. Pyzik, M. A. Ostrowski, J. N. Glickman, C. E. Rudd, H. L. Ploegh, A. Franke, G. A. Petsko, V. K. Kuchroo, and R. S. Blumberg, Erratum: Corrigendum: CEACAM1 regulates TIM-3-mediated tolerance and exhaustion, Nature, 536 (2016) 359.
• N. Saheb Sharif-Askari, F. Saheb Sharif-Askari, B. Mdkhana, S. al Heialy, H. S. Alsafar, R. Hamoudi, Q. Hamid, and R. Halwani, Enhanced expression of immune checkpoint receptors during SARS-CoV-2 viral infection, Mol Ther Methods Clin Dev, 20 (2021) 109-121.
• Y. Kimura, R. Tsunedomi, K. Yoshimura, S. Matsukuma, Y. Shindo, H. Matsui, Y. Tokumitsu, S. Yoshida, M. Iida, N. Suzuki, S. Takeda, T. Ioka, S. Hazama, and H. Nagano, Immune Evasion of Hepatoma Cancer Stem-Like Cells from Natural Killer Cells, Ann Surg Oncol, 29 (2022) 7423–7433.
• N. Kim, D. H. Lee, W. S. Choi, E. Yi, H. J. Kim, J. M. Kim, H. S. Jin, and H. S. Kim, Harnessing NK cells for cancer immunotherapy: immune checkpoint receptors and chimeric antigen receptors, BMB Rep, 54 (2021) 44-58.
• J. A. Marin-Acevedo, E. M. O. Kimbrough, and Y. Lou, Next generation of immune checkpoint inhibitors and beyond, J Hematol Oncol, 14 (2021) 45.
• W. M. Kim, Y. H. Huang, A. Gandhi, and R. S. Blumberg, CEACAM1 structure and function in immunity and its therapeutic implications, Semin Immunol, 42 (2019) 101296.
• T. Li, J. Fan, B. Wang, N. Traugh, Q. Chen, J. S. Liu, B. Li, and X. S. Liu, TIMER: A web server for comprehensive analysis of tumor-infiltrating immune cells, Cancer Res, 77 (2017) 108-110.
• Q. Lian, S. Wang, G. Zhang, D. Wang, G. Luo, J. Tang, L. Chen, and J. Gu, HCCDB: A Database of Hepatocellular Carcinoma Expression Atlas, Genomics Proteomics Bioinformatics, 16 (2018) 269-275.
• M. L. Speir, A. Bhaduri, N. S. Markov, P. Moreno, T. J. Nowakowski, I. Papatheodorou, A. A. Pollen, B. J. Raney, L. Seninge, W. J. Kent, and M. Haeussler, UCSC Cell Browser: Visualize your single-cell data, Bioinformatics, 37 (2021) 4578-4580.
• M. Yoshida, K. B. Worlock, N. Huang, R. G. H. Lindeboom, C. R. Butler, N. Kumasaka, C. Dominguez Conde, L. Mamanova, L. Bolt, L. Richardson, K. Polanski, E. Madissoon, J. L. Barnes, J. Allen-Hyttinen, E. Kilich, B. C. Jones, A. de Wilton, A. Wilbrey-Clark, W. Sungnak, J. P. Pett, J. Weller, E. Prigmore, H. Yung, P. Mehta, A. Saleh, A. Saigal, V. Chu, J. M. Cohen, C. Cane, A. Iordanidou, S. Shibuya, A. K. Reuschl, I. T. Herczeg, A. C. Argento, R. G. Wunderink, S. B. Smith, T. A. Poor, C. A. Gao, J. E. Dematte, G. R. S. Budinger, H. K. Donnelly, N. S. Markov, Z. Lu, G. Reynolds, M. Haniffa, G. S. Bowyer, M. Coates, M. R. Clatworthy, F. J. Calero-Nieto, B. Göttgens, C. O’Callaghan, N. J. Sebire, C. Jolly, P. de Coppi, C. M. Smith, A. v. Misharin, S. M. Janes, S. A. Teichmann, M. Z. Nikolić, and K. B. Meyer, Local and systemic responses to SARS-CoV-2 infection in children and adults, Nature, 602 (2022) 321-327.
• D. Warde-Farley, S. L. Donaldson, O. Comes, K. Zuberi, R. Badrawi, P. Chao, M. Franz, C. Grouios, F. Kazi, C. T. Lopes, A. Maitland, S. Mostafavi, J. Montojo, Q. Shao, G. Wright, G. D. Bader, and Q. Morris, The GeneMANIA prediction server: Biological network integration for gene prioritization and predicting gene function, Nucleic Acids Res, 38 (2010) 214-220.
• K. H. Stopsack, L. A. Mucci, E. S. Antonarakis, P. S. Nelson, and P. W. Kantoff, TMPRSS2 and COVID-19: Serendipity or opportunity for intervention?, Cancer Discov, 10 (2020) 779-782.
• Y. Fu, Y. Cheng, and Y. Wu, Understanding SARS-CoV-2-Mediated Inflammatory Responses: From Mechanisms to Potential Therapeutic Tools, Virol Sin, 35 (2020) 266-271.
• N. Curdy, O. Lanvin, C. Laurent, J. J. Fournié, and D. M. Franchini, Regulatory Mechanisms of Inhibitory Immune Checkpoint Receptors Expression, Trends Cell Biol, 29 (2019) 777-790.
• H. Brüssow, Immunology of COVID-19, Environ Microbiol, 22 (2020) 48954908.
• M. S. Abers, M. S. Lionakis, and D. P. Kontoyiannis, Checkpoint Inhibition and Infectious Diseases: A Good Thing?, Trends Mol Med, 25 (2019) 1080-1093.
• M. Dankner, S. D. Gray-Owen, Y. H. Huang, R. S. Blumberg, and N. Beauchemin, CEACAM1 as a multi-purpose target for cancer immunotherapy, Oncoimmunology, 6 (2017) 412-419.
• C. Pilard, M. Ancion, P. Delvenne, G. Jerusalem, P. Hubert, and M. Herfs, Cancer immunotherapy: it’s time to better predict patients’ response, Br J Cancer, 125 (2021) 927-938.
• L. M. McLane, M. S. Abdel-Hakeem, and E. J. Wherry, CD8 T Cell Exhaustion During Chronic Viral Infection and Cancer, Annu Rev Immunol, 37 (2019) 457-495.
• Z. Modabber, M. Shahbazi, R. Akbari, M. Bagherzadeh, A. Firouzjahi, and M. Mohammadnia-Afrouzi, TIM-3 as a potential exhaustion marker in CD4+ T cells of COVID-19 patients, Immun Inflamm Dis, 9 (2021) 1707-1715.
• H. S. C. Wong, C. L. Guo, G. H. Lin, K. Y. Lee, Y. Okada, and W. C. Chang, Transcriptome network analyses in human coronavirus infections suggest a rational use of immunomodulatory drugs for COVID-19 therapy, Genomics, 113 (2021) 564-575.
• M. Barnova, A. Bobcakova, V. Urdova, R. Kosturiak, L. Kapustova, D. Dobrota, and M. Jesenak, Inhibitory Immune Checkpoint Molecules and Exhaustion of T cells in COVID-19, Physiol Res, 70 (2021) 227-247.
• Y. Piao and X. Jin, Analysis of Tim-3 as a therapeutic target in prostate cancer, Tumor Biology, 39 (2017) 101104-101108.
• L. Xu, Y. Huang, L. Tan, W. Yu, D. Chen, C. Lu, J. He, G. Wu, X. Liu, and Y. Zhang, Increased Tim-3 expression in peripheral NK cells predicts a poorer prognosis and Tim-3 blockade improves NK cell-mediated cytotoxicity in human lung adenocarcinoma, Int Immunopharmacol, 29 (2015) 635-641.
• Y. Komohara, T. Morita, D. A. Annan, H. Horlad, K. Ohnishi, S. Yamada, T. Nakayama, S. Kitada, S. Suzu, I. Kinoshita, H. Dosaka-Akita, K. Akashi, M. Takeya, and M. Jinushi, The coordinated actions of TIM-3 on cancer and myeloid cells in the regulation of tumorigenicity and clinical prognosis in clear cell renal cell carcinomas, Cancer Immunol Res, 3 (2015) 999-1007.
• S. F. Ngiow, B. von Scheidt, H. Akiba, H. Yagita, M. W. L. Teng, and M. J. Smyth, Anti-TIM3 antibody promotes T cell IFN-γ-mediated antitumor immunity and suppresses established tumors, Cancer Res, 71 (2011) 3540-3551.
• B. Xu, L. Yuan, Q. Gao, P. Yuan, P. Zhao, H. Yuan, H. Fan, T. Li, P. Qin, L. Han, W. Fang, and Z. Suo, Circulating and tumor-infiltrating Tim-3 in patients with colorectal cancer, Oncotarget, 6 (2015) 20592-20603.
• K. Sakuishi, L. Apetoh, J. M. Sullivan, B. R. Blazar, V. K. Kuchroo, and A. C. Anderson, Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity, Journal of Experimental Medicine, 207 (2010) 2187-2194.