Skip to main content

Advertisement

SpringerLink
Log in

Diagnostic, prognostic, and immunological roles of CD177 in cervical cancer

  • Research
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Background

CD177, an indicator of prognosis in diverse cancers, is involved in the physiological processes of various tumor cells, and acts as an immune molecule with novel functions in cancer pathogenesis. However, the diagnostic, prognostic, and immunological role of CD177 in cervical cancer remains unclear.

Methods

Utilizing publicly available databases and integrating several bioinformatics analysis methods, we evaluated the expression level of CD177 in cervical cancer by GENT2, HPA, and GEO databases. And the experiments of western blot and immunohistochemical staining were used to test the hypothesis. The Kaplan–Meier Plotter database, Xena Shiny, and the constructed nomogram were clearly demonstrated its prognostic value for patients. Gene set enrichment analysis explored the relationship between CD177 and cervical cancer immune responses and immune cells infiltration level. In addition, we investigated the association between CD177 expression and stromal score, immune score, immune checkpoint, and drug sensitivity by TCGA RNA-seq data.

Results

CD177 was apparently expressed at low levels in cervical cancer and predicted a poor survival rate for patients. CD177 significantly activated immune-related signaling pathways and had a positive relationship with immune cell infiltration level. The high CD177 expression group possessed the high stromal score and immune score. CD177 had potential interactions with CTLA4, CD27, BLTA, CD200R1, CD80, NRP1, TNFRSF25, TIGIT, ICOS, and TNFSF9 checkpoint markers. And CD177 expression was positively relevant with drug sensitivity for Lapatinib, Belinostat, ATRA, Gefitinib, Navitoclax, and Tamoxifen.

Significance

These findings may shed light on the vital role of CD177 in cervical cancer diagnosis, prognosis, and immunological functions, and it may be a promising predictor and potential factor for cervical cancer patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

Data availability

Public datasets were obtained from GENT2 ( http://gent2.appex.kr/gent2/), HPA (https://www.proteinatlas.org/), GEO database (https://www.ncbi.nlm.nih.gov/geo/) Kaplan–Meier Plotter websites (https://kmplot.com/analysis/), Xena Shiny (https://shiny.hiplot.com.cn/ucsc-xena-shiny/), TCGA (https://portal.gdc.cancer.gov/), LinkedOmics (http://linkedomics.org/admin.php), STRING database (https://string-db.org/), TISIDB (http://cis.hku.hk/TISIDB/), and TIMER (https://cistrome.shinyapps.io/timer/).

Abbreviations

GO:

Gene ontology

KEGG:

Kyoto encyclopedia of genes and genomes

GSEA:

Gene set enrichment analysis

TCGA:

The cancer genome atlas

OS:

Overall survival

PFS:

Progress-free survival

PFI:

Progression-free interval

DFI:

Disease-free interval

DEGs:

Differentially expressed genes

SCNA:

Somatic copy-number alterations

ACC:

Adrenocortical carcinoma

BLCA:

Bladder urothelial carcinoma

BRCA:

Breast invasive carcinoma

CESC:

Cervical squamous cell carcinoma and endocervical adenocarcinoma

CHOL:

Cholangiocarcinoma

COAD:

Colon adenocarcinoma

DLBC:

Lymphoid neoplasm diffuse large B-cell lymphoma

ESCA:

Esophageal carcinoma

GBM:

Glioblastoma multiforme

HNSC:

Head and neck squamous cell carcinoma

KICH:

Kidney chromophobe

KIRC:

Kidney renal clear cell carcinoma

KIRP:

Kidney renal papillary cell carcinoma

LAML:

Acute myeloid leukemia

LGG:

Brain lower grade glioma

LIHC:

Liver hepatocellular carcinoma

LUAD:

Lung adenocarcinoma

LUSC:

Lung squamous cell carcinoma

MESO:

Mesothelioma

OV:

Ovarian serous cystadenocarcinoma

PAAD:

Pancreatic adenocarcinoma

PCPG:

Pheochromocytoma and Paraganglioma

PRAD:

Prostate adenocarcinoma

READ:

Rectum adenocarcinoma

SARC:

Sarcoma

SKCM:

Skin cutaneous melanoma

STAD:

Stomach adenocarcinoma

TGCT:

Testicular germ cell tumors

THCA:

Thyroid carcinoma

THYM:

Thymoma

UCEC:

Uterine corpus endometrial carcinoma

UCS:

Uterine carcinosarcoma

UVM:

Uveal melanoma

References

  • Alayed K, Meyerson JB, Osei ES, Blidaru G, Schlegelmilch J, Johnson M, Meyerson HJ (2020) CD177 enhances the detection of myelodysplastic syndrome by flow cytometry. Am J Clin Pathol 153:554–565

    Article  CAS  Google Scholar 

  • Bai M, Grieshaber-Bouyer R, Wang J, Schmider AB, Wilson ZS, Zeng L, Halyabar O, Godin MD, Nguyen HN, Levescot A et al (2017) CD177 modulates human neutrophil migration through activation-mediated integrin and chemoreceptor regulation. Blood 130:2092–2100

    Article  CAS  Google Scholar 

  • Bilancia D, Rosati G, Dinota A, Germano D, Romano R, Manzione L (2007) Lapatinib in breast cancer. Ann Oncol. https://doi.org/10.1093/annonc/mdm220

    Article  Google Scholar 

  • Cohen AC, Roane BM, Leath CA (2020) Novel therapeutics for recurrent cervical cancer: moving towards personalized therapy. Drugs 80:217–227

    Article  Google Scholar 

  • Eckschlager T, Plch J, Stiborova M, Hrabeta J (2017) Histone deacetylase inhibitors as anticancer drugs. Int J Mol Sci. https://doi.org/10.3390/ijms18071414

    Article  Google Scholar 

  • Eulenberg-Gustavus C, Bähring S, Maass PG, Luft FC, Kettritz R (2017) Gene silencing and a novel monoallelic expression pattern in distinct CD177 neutrophil subsets. J Exp Med 214:2089–2101

    Article  Google Scholar 

  • Győrffy B (2021) Survival analysis across the entire transcriptome identifies biomarkers with the highest prognostic power in breast cancer. Comput Struct Biotechnol J 19:4101–4109

    Article  Google Scholar 

  • Hosomi Y, Morita S, Sugawara S, Kato T, Fukuhara T, Gemma A, Takahashi K, Fujita Y, Harada T, Minato K et al (2020) Gefitinib Alone Versus Gefitinib Plus chemotherapy for non-small-cell lung cancer with mutated epidermal growth factor receptor: NEJ009 study. J Clin Oncol 38:115–123

    Article  CAS  Google Scholar 

  • Jiang J, Chen Y, Zhang M, Zhou H, Wu H (2020) Relationship between CD177 and the vasculogenic mimicry, clinicopathological parameters, and prognosis of epithelial ovarian cancer. Ann Palliat Med 9:3985–3992

    Article  Google Scholar 

  • Kim M-C, Borcherding N, Ahmed KK, Voigt AP, Vishwakarma A, Kolb R, Kluz PN, Pandey G, De U, Drashansky T et al (2021) CD177 modulates the function and homeostasis of tumor-infiltrating regulatory T cells. Nat Commun 12:5764

    Article  CAS  Google Scholar 

  • Kissel K, Santoso S, Hofmann C, Stroncek D, Bux J (2001) Molecular basis of the neutrophil glycoprotein NB1 (CD177) involved in the pathogenesis of immune neutropenias and transfusion reactions. Eur J Immunol 31:1301–1309

    Article  CAS  Google Scholar 

  • Kluz PN, Kolb R, Xie Q, Borcherding N, Liu Q, Luo Y, Kim M-C, Wang L, Zhang Y, Li W et al (2020) Cancer cell-intrinsic function of CD177 in attenuating β-catenin signaling. Oncogene 39:2877–2889

    Article  CAS  Google Scholar 

  • Li B, Severson E, Pignon J-C, Zhao H, Li T, Novak J, Jiang P, Shen H, Aster JC, Rodig S et al (2016) Comprehensive analyses of tumor immunity: implications for cancer immunotherapy. Genome Biol 17:174

    Article  Google Scholar 

  • Li T, Fan J, Wang B, Traugh N, Chen Q, Liu JS, Li B, Liu XS (2017) TIMER: a web server for comprehensive analysis of tumor-infiltrating immune cells. Cancer Res 77:e108–e110

    Article  CAS  Google Scholar 

  • Liang Y, Wang W, Zhu X, Yu M, Zhou C (2022) Inhibition of myeloid-derived suppressive cell function with all-trans retinoic acid enhanced anti-PD-L1 efficacy in cervical cancer. Sci Rep 12:9619

    Article  CAS  Google Scholar 

  • Liu Q, Zhang C, Ma G, Zhang Q (2014) Expression of SPRR3 is associated with tumor cell proliferation and invasion in glioblastoma multiforme. Oncol Lett 7:427–432

    Article  Google Scholar 

  • Luo H, Xu X, Yang J, Wang K, Wang C, Yang P, Cai H (2020) Genome-wide somatic copy number alteration analysis and database construction for cervical cancer. Mol Genet Genomics 295:765–773

    Article  CAS  Google Scholar 

  • Mandal R, Chan TA (2016) Personalized oncology meets immunology: the path toward precision immunotherapy. Cancer Discov 6:703–713

    Article  CAS  Google Scholar 

  • Monk BJ, Pandite LN (2011) Survival data from a phase II, open-label study of pazopanib or lapatinib monotherapy in patients with advanced and recurrent cervical cancer. J Clin Oncol 29:4845

    Article  Google Scholar 

  • Moreira LF, Maino MM, Garbin HI, Da Natividade GR, Volkweis BS, Kulczynski JU (2018) CD117 Expression in squamous cell carcinoma of the Oesophagus. Anticancer Res 38:3929–3933

    Article  CAS  Google Scholar 

  • Odiase O, Noah-Vermillion L, Simone BA, Aridgides PD (2021) The incorporation of immunotherapy and targeted therapy into chemoradiation for cervical cancer: a focused review. Front Oncol 11:663749

    Article  Google Scholar 

  • Otter SJ, Chatterjee J, Stewart AJ, Michael A (2019) The role of biomarkers for the prediction of response to checkpoint immunotherapy and the rationale for the use of checkpoint immunotherapy in cervical cancer. Clin Oncol 31:834–843

    Article  CAS  Google Scholar 

  • Park S-J, Yoon B-H, Kim S-K, Kim S-Y (2019) GENT2: an updated gene expression database for normal and tumor tissues. BMC Med Genomics 12:101

    Article  Google Scholar 

  • Rosen VM, Guerra I, McCormack M, Nogueira-Rodrigues A, Sasse A, Munk VC, Shang A (2017) Systematic review and network meta-analysis of bevacizumab plus first-line Topotecan-Paclitaxel or cisplatin-paclitaxel versus non-bevacizumab-containing therapies in persistent, recurrent, or metastatic cervical cancer. Int J Gynecol Cancer 27:1237–1246

    Article  Google Scholar 

  • Ru B, Wong CN, Tong Y, Zhong JY, Zhong SSW, Wu WC, Chu KC, Wong CY, Lau CY, Chen I et al (2019) TISIDB: an integrated repository portal for tumor-immune system interactions. Bioinformatics 15(35):4200–4202 (Epub 2019/03/25)

    Article  Google Scholar 

  • Schiffmann LM, Fritsch M, Gebauer F, Günther SD, Stair NR, Seeger JM, Thangarajah F, Dieplinger G, Bludau M, Alakus H et al (2019) Tumour-infiltrating neutrophils counteract anti-VEGF therapy in metastatic colorectal cancer. Br J Cancer 120:69–78

    Article  CAS  Google Scholar 

  • Silvestre-Roig C, Hidalgo A, Soehnlein O (2016) Neutrophil heterogeneity: implications for homeostasis and pathogenesis. Blood 127:2173–2181

    Article  CAS  Google Scholar 

  • Silvestre-Roig C, Fridlender ZG, Glogauer M, Scapini P (2019) Neutrophil diversity in health and disease. Trends Immunol 40:565–583

    Article  CAS  Google Scholar 

  • Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F (2021) Global cancer statistics 2020: globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71:209–249

    Article  Google Scholar 

  • Szklarczyk D, Gable AL, Lyon D, Junge A, Wyder S, Huerta-Cepas J, Simonovic M, Doncheva NT, Morris JH, Bork P, Jensen LJ, von Mering C (2019) STRING v11: protein–protein association networks with increased coverage supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Research 47(D1):D607–D613. https://doi.org/10.1093/nar/gky1131

  • Uhlen M, Zhang C, Lee S, Sjöstedt E, Fagerberg L, Bidkhori G, Benfeitas R, Arif M, Liu Z, Edfors F, Sanli K, von Feilitzen K, Oksvold P, Lundberg E, Hober S, Nilsson P, Mattsson J, Schwenk JM, Brunnström H, Glimelius B, Sjöblom T, Edqvist PH, Djureinovic D, Micke P, Lindskog C, Mardinoglu A, Ponten F (2017) A pathology atlas of the human cancer transcriptome. Sci 357(6352):eaan2507. https://doi.org/10.1126/science.aan2507

  • Vasaikar SV, Straub P, Wang J, Zhang B (2018) LinkedOmics: analyzing multi-omics data within and across 32 cancer types. Nucleic Acids Res 46:D956–D963

    Article  CAS  Google Scholar 

  • Wang S, Xiong Y, Zhao L, Gu K, Li Y, Zhao F, Li J, Wang M, Wang H, Tao Z et al (2021) UCSCXenaShiny: An R/CRAN Package for Interactive analysis of UCSC Xena Data. Bioinformatics. https://doi.org/10.1093/bioinformatics/btab561

    Article  Google Scholar 

  • Wendel Naumann R, Leath CA (2020) Advances in immunotherapy for cervical cancer. Curr Opin Oncol 32:481–487

    Article  CAS  Google Scholar 

  • Zack TI, Schumacher SE, Carter SL, Cherniack AD, Saksena G, Tabak B, Lawrence MS, Zhsng C-Z, Wala J, Mermel CH et al (2013) Pan-cancer patterns of somatic copy number alteration. Nat Genet 45:1134–1140

    Article  CAS  Google Scholar 

  • Zhang Y, Zhang Z (2020) The history and advances in cancer immunotherapy: understanding the characteristics of tumor-infiltrating immune cells and their therapeutic implications. Cell Mol Immunol 17:807–821

    Article  CAS  Google Scholar 

  • Zhang X, Zhang R, Chen H, Wang L, Ren C, Pataer A, Wu S, Meng QH, Ha MJ, Morris J et al (2020) KRT-232 and navitoclax enhance trametinib’s anti-Cancer activity in non-small cell lung cancer patient-derived xenografts with KRAS mutations. Am J Cancer Res 10:4464–4475

    CAS  Google Scholar 

  • Zhou C, Guo Z, Xu L, Jiang H, Sun P, Zhu X, Mu X (2020) PFND1 predicts poor prognosis of gastric cancer and promotes cell metastasis by activating the Wnt/β-catenin pathway. Onco Targets Ther 13:3177–3186

    Article  CAS  Google Scholar 

Download references

Funding

This work was supported by the Natural Science Foundation of Hubei Province of China (2021CFB430).

Author information

Author notes

  1. Wenxin Liao and Wei Li have equally contributed to this work.

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, China

    Wenxin Liao, Wei Li, Yang Li, Tingting Liu, Ying Wang, Dan Feng & Fujin Shen

Authors
  1. Wenxin Liao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wei Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yang Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tingting Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ying Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Dan Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Fujin Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by [WL], [WL], [YL], [TL], [YW], [DF], and [FS]. The first draft of the manuscript was written by [WL] and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Fujin Shen.

Ethics declarations

Competing interests

The authors declare no competing interests.

Conflict of interest

The authors report no conflicts of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liao, W., Li, W., Li, Y. et al. Diagnostic, prognostic, and immunological roles of CD177 in cervical cancer. J Cancer Res Clin Oncol 149, 173–189 (2023). https://doi.org/10.1007/s00432-022-04465-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00432-022-04465-5

Keywords

Search

Navigation