Login Register Cart 0
Generic placeholder image

Current Proteomics

Editor-in-Chief

ISSN (Print): 1570-1646
ISSN (Online): 1875-6247

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

A Pan-Cancer Signature For S100A11 - Prognostic And Immunotherapeutic Value

Author(s): Yali Le, Chenchen Geng, Guanghui Zhao, Xiaoqian Gao, Shuzhen Zhu, Ziqian Liu and Ping Zhang*

Volume 20, Issue 1, 2023

Published on: 01 June, 2023

Page: [62 - 74] Pages: 13

DOI: 10.2174/1570164620666230503163349

open access plus

conference banner
Abstract

Background: S100 calcium-binding protein A11 (S100A11) has important roles in tumorigenesis and multiple cancer progression.

Aims: In this study, we aimed to analyze the expression and prognostic value of S100A11 across cancers and further explore the relationship between S100A11 and the tumor immune microenvironment.

Methods: We analyzed the differential expression of S100A11 in the TIMER, GEPIA, and BioGPS databases and searched for its prognostic impact in the GEPIA and Kaplan-Meier plotter databases. We used the SangerBox database to investigate the relationship between S100A11 expression and the tumor immune microenvironment. The TIMER database explored the relationship between S100A11 expression and tumor immune-infiltrated cells (TILs). Correlation analysis of S100A11 expression with clinical parameters in thyroid carcinoma (THCA) was performed using the UALCAN database. The co-expression network of S100A11 in THCA was explored through the LinkedOmics database. RT‒qPCR and immunohistochemical (IHC) staining were used to analyze the expression level of S100A11 in THCA.

Results: S100A11 expression was higher in many tumors than in paired normal tissues, and increased expression was associated with poor prognosis, including overall survival (OS), recurrence-free survival (RFS), and disease-free survival (DFS). S100A11 was differentially expressed in immune subtypes and molecular subtypes of some cancers. The expression of S100A11 was correlated with immune checkpoints (ICP), tumor mutational burden (TMB), microsatellite instability (MSI), neoantigens, and TILs. The methylation level of S100A11 was negatively correlated with mRNA expression. S100A11 expression had a specific correlation with the clinical parameters of THCA. In THCA, the coexpression network of S100A11 was mainly involved in regulating inflammation and immune responses. RT‒qPCR and IHC staining confirmed that S100A11 was upregulated in THCA.

Conclusion: S100A11 may be related to the regulation of the tumor microenvironment. S100A11 may serve as a potential pan-cancer biomarker for prognosis. S100A11 could be a potential target for THCA immunotherapy.

Keywords: S100A11, cancer, prognosis, immunotherapy, thyroid carcinoma, RT-qPCR, tumor mutational burden (TMB).

« Previous Next »
Graphical Abstract

[1]
He, H.; Li, J.; Weng, S.; Li, M.; Yu, Y. S100A11: Diverse function and pathology corresponding to different target proteins. Cell Biochem. Biophys., 2009, 55(3), 117-126.
[http://dx.doi.org/10.1007/s12013-009-9061-8] [PMID: 19649745]
[2]
Salama, I.; Malone, P.S.; Mihaimeed, F.; Jones, J.L. A review of the S100 proteins in cancer. Eur. J. Surg. Oncol., 2008, 34(4), 357-364.
[http://dx.doi.org/10.1016/j.ejso.2007.04.009] [PMID: 17566693]
[3]
Leclerc, E.; Fritz, G.; Vetter, S.W.; Heizmann, C.W. Binding of S100 proteins to RAGE: An update. Biochim. Biophys. Acta Mol. Cell Res., 2009, 1793(6), 993-1007.
[http://dx.doi.org/10.1016/j.bbamcr.2008.11.016] [PMID: 19121341]
[4]
Donato, R. S100: A multigenic family of calcium-modulated proteins of the EF-hand type with intracellular and extracellular functional roles. Int. J. Biochem. Cell Biol., 2001, 33(7), 637-668.
[http://dx.doi.org/10.1016/S1357-2725(01)00046-2] [PMID: 11390274]
[5]
Sakaguchi, M.; Miyazaki, M.; Takaishi, M.; Sakaguchi, Y.; Makino, E.; Kataoka, N.; Yamada, H.; Namba, M.; Huh, N. S100C/A11 is a key mediator of Ca2+-induced growth inhibition of human epidermal keratinocytes. J. Cell Biol., 2003, 163(4), 825-835.
[http://dx.doi.org/10.1083/jcb.200304017] [PMID: 14623863]
[6]
Sakaguchi, M.; Sonegawa, H.; Murata, H.; Kitazoe, M.; Futami, J.; Kataoka, K.; Yamada, H.; Huh, N. S100A11, an dual mediator for growth regulation of human keratinocytes. Mol. Biol. Cell, 2008, 19(1), 78-85.
[http://dx.doi.org/10.1091/mbc.e07-07-0682] [PMID: 17978094]
[7]
Kondo, A.; Sakaguchi, M.; Makino, E.; Namba, M.; Okada, S.; Huh, N.H. Localization of S100C immunoreactivity in various human tissues. Acta Med. Okayama, 2002, 56(1), 31-34.
[PMID: 11873942]
[8]
Memon, A.A.; Sorensen, B.S.; Meldgaard, P.; Fokdal, L.; Thykjaer, T.; Nexo, E. Down-regulation of S100C is associated with bladder cancer progression and poor survival. Clin. Cancer Res., 2005, 11(2), 606-611.
[http://dx.doi.org/10.1158/1078-0432.606.11.2] [PMID: 15701847]
[9]
Wang, C.; Luo, J.; Rong, J.; He, S.; Zhang, L.; Zheng, F. Distinct prognostic roles of S100 mRNA expression in gastric cancer. Pathol. Res. Pract., 2019, 215(1), 127-136.
[http://dx.doi.org/10.1016/j.prp.2018.10.034] [PMID: 30414696]
[10]
Cui, Y.; Li, L.; Li, Z.; Yin, J.; Lane, J.; Ji, J.; Jiang, W.G. Dual effects of targeting S100A11 on suppressing cellular metastatic properties and sensitizing drug response in gastric cancer. Cancer Cell Int., 2021, 21(1), 243.
[http://dx.doi.org/10.1186/s12935-021-01949-1] [PMID: 33931048]
[11]
Zhuang, H.; Chen, X.; Dong, F.; Zhang, Z.; Zhou, Z.; Ma, Z.; Huang, S.; Chen, B.; Zhang, C.; Hou, B. Prognostic values and immune suppression of the S100A family in pancreatic cancer. J. Cell. Mol. Med., 2021, 25(6), 3006-3018.
[http://dx.doi.org/10.1111/jcmm.16343] [PMID: 33580614]
[12]
Zeng, M.L.; Zhu, X.J.; Liu, J.; Shi, P.C.; Kang, Y.L.; Lin, Z.; Cao, Y.P. An integrated bioinformatic analysis of the S100 gene family for the prognosis of colorectal cancer. BioMed Res. Int., 2020, 2020, 1-15.
[http://dx.doi.org/10.1155/2020/4746929] [PMID: 33294444]
[13]
Zheng, S.; Liu, L.; Xue, T.; Jing, C.; Xu, X.; Wu, Y.; Wang, M.; Xie, X.; Zhang, B. Comprehensive analysis of the prognosis and correlations with immune infiltration of s100 protein family members in hepatocellular carcinoma. Front. Genet., 2021, 12, 648156.
[http://dx.doi.org/10.3389/fgene.2021.648156] [PMID: 33815482]
[14]
Sato, H.; Sakaguchi, M.; Yamamoto, H.; Tomida, S.; Aoe, K.; Shien, K.; Yoshioka, T.; Namba, K.; Torigoe, H.; Soh, J.; Tsukuda, K.; Tao, H.; Okabe, K.; Miyoshi, S.; Pass, H.I.; Toyooka, S. Therapeutic potential of targeting S100A11 in malignant pleural mesothelioma. Oncogenesis, 2018, 7(1), 11.
[http://dx.doi.org/10.1038/s41389-017-0017-3] [PMID: 29362358]
[15]
Chang, Y.; Li, N.; Yuan, W.; Wang, G.; Wen, J. LINC00997, a novel long noncoding RNA, contributes to metastasis via regulation of S100A11 in kidney renal clear cell carcinoma. Int. J. Biochem. Cell Biol., 2019, 116, 105590.
[http://dx.doi.org/10.1016/j.biocel.2019.105590] [PMID: 31442606]
[16]
Wang, H.; Yin, M.; Ye, L.; Gao, P.; Mao, X.; Tian, X.; Xu, Z.; Dai, X.; Cheng, H. S100A11 Promotes glioma cell proliferation and predicts grade-correlated unfavorable prognosis. Technol. Cancer Res. Treat., 2021, 20.
[http://dx.doi.org/10.1177/15330338211011961] [PMID: 33902363]
[17]
Meng, M.; Sang, L.; Wang, X. S100 calcium binding protein A11 (S100A11) promotes the proliferation, migration and invasion of cervical cancer cells, and activates Wnt/β-catenin signaling. OncoTargets Ther., 2019, 12, 8675-8685.
[http://dx.doi.org/10.2147/OTT.S225248] [PMID: 31695426]
[18]
Zhang, L.; Zhu, T.; Miao, H.; Liang, B. The calcium binding protein S100A11 and its roles in diseases. Front. Cell Dev. Biol., 2021, 9, 693262.
[http://dx.doi.org/10.3389/fcell.2021.693262] [PMID: 34179021]
[19]
Gocheva, V.; Naba, A.; Bhutkar, A.; Guardia, T.; Miller, K.M.; Li, C.M.C.; Dayton, T.L.; Sanchez-Rivera, F.J.; Kim-Kiselak, C.; Jailkhani, N.; Winslow, M.M.; Del Rosario, A.; Hynes, R.O.; Jacks, T. Quantitative proteomics identify Tenascin-C as a promoter of lung cancer progression and contributor to a signature prognostic of patient survival. Proc. Natl. Acad. Sci. USA, 2017, 114(28), E5625-E5634.
[http://dx.doi.org/10.1073/pnas.1707054114] [PMID: 28652369]
[20]
Woo, T.; Okudela, K.; Mitsui, H.; Tajiri, M.; Rino, Y.; Ohashi, K.; Masuda, M. Up-regulation of s100a11 in lung adenocarcinoma – its potential relationship with cancer progression. PLoS One, 2015, 10(11), e0142642.
[http://dx.doi.org/10.1371/journal.pone.0142642] [PMID: 26544866]
[21]
Liu, L.; Miao, L.; Liu, Y.; Qi, A.; Xie, P.; Chen, J.; Zhu, H. S100A11 regulates renal carcinoma cell proliferation, invasion, and migration via the EGFR/Akt signaling pathway and E-cadherin. Tumour Biol., 2017, 39(5)
[http://dx.doi.org/10.1177/1010428317705337] [PMID: 28513300]
[22]
Guo, M.L.; Sun, M.X.; Lan, J.Z.; Yan, L.S.; Zhang, J.J.; Hu, X.X.; Xu, S.; Mao, D.H.; Yang, H.S.; Liu, Y.W.; Chen, T.X. Proteomic analysis of the effects of cell culture density on the metastasis of breast cancer cells. Cell Biochem. Funct., 2019, 37(2), 72-83.
[http://dx.doi.org/10.1002/cbf.3377] [PMID: 30773657]
[23]
Raphaël, M.; Lehen’kyi, V.; Vandenberghe, M.; Beck, B.; Khalimonchyk, S.; Vanden Abeele, F.; Farsetti, L.; Germain, E.; Bokhobza, A.; Mihalache, A.; Gosset, P.; Romanin, C.; Clézardin, P.; Skryma, R.; Prevarskaya, N. TRPV6 calcium channel translocates to the plasma membrane via Orai1-mediated mechanism and controls cancer cell survival. Proc. Natl. Acad. Sci., 2014, 111(37), E3870-E3879.
[http://dx.doi.org/10.1073/pnas.1413409111] [PMID: 25172921]
[24]
Hu, F.F.; Liu, C.J.; Liu, L.L.; Zhang, Q.; Guo, A.Y. Expression profile of immune checkpoint genes and their roles in predicting immunotherapy response. Brief. Bioinform., 2021, 22(3), bbaa176.
[http://dx.doi.org/10.1093/bib/bbaa176] [PMID: 32814346]
[25]
Suzuki, S.; Ishida, T.; Yoshikawa, K.; Ueda, R. Current status of immunotherapy. Jpn. J. Clin. Oncol., 2016, 46(3), 191-203.
[http://dx.doi.org/10.1093/jjco/hyv201] [PMID: 26819277]
[26]
Washah, H.N.; Salifu, E.Y.; Soremekun, O.; Elrashedy, A.A.; Munsamy, G.; Olotu, F.A.; Soliman, M.E.S. Integrating bioinformatics strategies in cancer immunotherapy: current and future perspectives. Comb. Chem. High Throughput Screen., 2020, 23(8), 687-698.
[http://dx.doi.org/10.2174/1386207323666200427113734] [PMID: 32338212]
[27]
Low, S.K.; Nakamura, Y. The road map of cancer precision medicine with the innovation of advanced cancer detection technology and personalized immunotherapy. Jpn. J. Clin. Oncol., 2019, 49(7), 596-603.
[http://dx.doi.org/10.1093/jjco/hyz073] [PMID: 31135897]
[28]
Xu, R.; Richards, F.M. Development of in vitro co-culture model in anti-cancer drug development cascade. Comb. Chem. High Throughput Screen., 2017, 20(5), 451-457.
[PMID: 28155598]
[29]
Galdiero, M.R.; Varricchi, G.; Marone, G. The immune network in thyroid cancer. OncoImmunology, 2016, 5(6), e1168556.
[http://dx.doi.org/10.1080/2162402X.2016.1168556] [PMID: 27471646]
[30]
Kalluri, R. The biology and function of fibroblasts in cancer. Nat. Rev. Cancer, 2016, 16(9), 582-598.
[http://dx.doi.org/10.1038/nrc.2016.73] [PMID: 27550820]
[31]
Ravelli, A.; Roviello, G.; Cretella, D.; Cavazzoni, A.; Biondi, A.; Cappelletti, M.R.; Zanotti, L.; Ferrero, G.; Ungari, M.; Zanconati, F.; Bottini, A.; Alfieri, R.; Petronini, P.G.; Generali, D. Tumor-infiltrating lymphocytes and breast cancer: Beyond the prognostic and predictive utility. Tumour Biol., 2017, 39(4)
[http://dx.doi.org/10.1177/1010428317695023] [PMID: 28378631]
[32]
Wouters, M.C.A.; Nelson, B.H. Prognostic significance of tumor-infiltrating B cells and plasma cells in human cancer. Clin. Cancer Res., 2018, 24(24), 6125-6135.
[http://dx.doi.org/10.1158/1078-0432.CCR-18-1481] [PMID: 30049748]
[33]
Poch, M.; Hall, M.; Joerger, A.; Kodumudi, K.; Beatty, M.; Innamarato, P.P.; Bunch, B.L.; Fishman, M.N.; Zhang, J.; Sexton, W.J.; Pow-Sang, J.M.; Gilbert, S.M.; Spiess, P.E.; Dhillon, J.; Kelley, L.; Mullinax, J.; Sarnaik, A.A.; Pilon-Thomas, S. Expansion of Tumor Infiltrating Lymphocytes (TIL) from bladder cancer. OncoImmunology, 2018, 7(9), e1476816.
[http://dx.doi.org/10.1080/2162402X.2018.1476816] [PMID: 30228944]
[34]
Azimi, F.; Scolyer, R.A.; Rumcheva, P.; Moncrieff, M.; Murali, R.; McCarthy, S.W.; Saw, R.P.; Thompson, J.F. Tumor-infiltrating lymphocyte grade is an independent predictor of sentinel lymph node status and survival in patients with cutaneous melanoma. J. Clin. Oncol., 2012, 30(21), 2678-2683.
[http://dx.doi.org/10.1200/JCO.2011.37.8539] [PMID: 22711850]
[35]
Aran, D.; Sirota, M.; Butte, A.J. Systematic pan-cancer analysis of tumour purity. Nat. Commun., 2015, 6(1), 8971.
[http://dx.doi.org/10.1038/ncomms9971] [PMID: 26634437]
[36]
Anania, M.C.; Miranda, C.; Vizioli, M.G.; Mazzoni, M.; Cleris, L.; Pagliardini, S.; Manenti, G.; Borrello, M.G.; Pierotti, M.A.; Greco, A. S100A11 overexpression contributes to the malignant phenotype of papillary thyroid carcinoma. J. Clin. Endocrinol. Metab., 2013, 98(10), E1591-E1600.
[http://dx.doi.org/10.1210/jc.2013-1652] [PMID: 23928665]
[37]
Jaiswal, J.K.; Lauritzen, S.P.; Scheffer, L.; Sakaguchi, M.; Bunkenborg, J.; Simon, S.M.; Kallunki, T.; Jäättelä, M.; Nylandsted, J. S100A11 is required for efficient plasma membrane repair and survival of invasive cancer cells. Nat. Commun., 2014, 5(1), 3795.
[http://dx.doi.org/10.1038/ncomms4795] [PMID: 24806074]
[38]
Sobolewski, C.; Abegg, D.; Berthou, F.; Dolicka, D.; Calo, N.; Sempoux, C.; Fournier, M.; Maeder, C.; Ay, A.S.; Clavien, P.A.; Humar, B.; Dufour, J.F.; Adibekian, A.; Foti, M. S100A11/ANXA2 belongs to a tumour suppressor/oncogene network deregulated early with steatosis and involved in inflammation and hepatocellular carcinoma development. Gut, 2020, 69(10), 1841-1854.
[http://dx.doi.org/10.1136/gutjnl-2019-319019] [PMID: 31919231]

Rights & Permissions Print Cite
Article Metrics
30
3
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy