Prognostic Implications of the Complement Protein C1Q and Its Correlation with Immune Infiltrates in Osteosarcoma

Overview

Journal Onco Targets Ther

Publisher Dove Medical Press

Specialty Oncology

Date 2021 Mar 12

PMID 33707956

Citations 10

Authors

Hanji Huang

Manli Tan

Li Zheng

Guohua Yan

Kanglu Li

Dejie Lu

Xiaofei Cui

Si He

Danqing Lei

Bo Zhu

Jinmin Zhao

Affiliations

Soon will be listed here.

Abstract

Background: Osteosarcoma (OS) is the most widespread bone tumour among childhood cancers, and distant metastasis is the dominant factor in poor prognosis for patients with OS. Therefore, it is necessary to identify new prognostic biomarkers for identifying patients with aggressive disease.

Methods: Two OS datasets (GSE21257 and GSE33383) were downloaded from the Gene Expression Omnibus (GEO) and subsequently subjected to weighted gene co-expression network analysis (WGCNA) and differential gene expression analysis (DGE) to screen candidate genes. A prognostic model was constructed using OS data derived from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) program to further screen key genes and perform gene ontology (GO) analysis. The prognostic values of key genes were assessed using the Kaplan-Meier (KM) plotter. The GEO dataset was used for immune infiltration analysis and association analysis of key genes. In addition, quantitative real-time polymerase chain reaction (qRT-PCR) was employed to validate the expression levels of potentially crucial genes in OS cell lines.

Results: In the present study, we found 114 genes with a highly significant correlation in the module and 44 downregulated genes; 25 candidate genes overlapped in the two parts of the genes. Among these, three key genes, , , and , were the most significant hub genes, which had the highest node degrees, were clustered into one group, and implicated in most significant biological processes (regulation of immune effector process). Moreover, these three key genes were negatively associated with the prognosis of OS and positively associated with three immune cells (follicular helper T cells, memory B cells, and CD8 T cells). Additionally, compared to non-metastatic OS cell lines, the expression of three key genes was significantly downregulated in metastatic OS cell lines.

Conclusion: Our results revealed that three key genes (, , and were implicated in tumour immune infiltration and may be promising biomarkers for predicting metastasis and prognosis of patients with OS.

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References

Yu D, Ruan X, Huang J, Hu W, Chen C, Xu Y . Comprehensive Analysis of Competitive Endogenous RNAs Network, Being Associated With Esophageal Squamous Cell Carcinoma and Its Emerging Role in Head and Neck Squamous Cell Carcinoma. Front Oncol. 2020; 9:1474. PMC: 6985543. DOI: 10.3389/fonc.2019.01474. View

Inagaki Y, Hookway E, Williams K, Hassan A, Oppermann U, Tanaka Y . Dendritic and mast cell involvement in the inflammatory response to primary malignant bone tumours. Clin Sarcoma Res. 2016; 6:13. PMC: 4968446. DOI: 10.1186/s13569-016-0053-3. View

Bandini S, Macagno M, Hysi A, Lanzardo S, Conti L, Bello A . The non-inflammatory role of C1q during Her2/neu-driven mammary carcinogenesis. Oncoimmunology. 2017; 5(12):e1253653. PMC: 5214935. DOI: 10.1080/2162402X.2016.1253653. View

Agostinis C, Vidergar R, Belmonte B, Mangogna A, Amadio L, Geri P . Complement Protein C1q Binds to Hyaluronic Acid in the Malignant Pleural Mesothelioma Microenvironment and Promotes Tumor Growth. Front Immunol. 2017; 8:1559. PMC: 5701913. DOI: 10.3389/fimmu.2017.01559. View

Bulla R, Tripodo C, Rami D, Ling G, Agostinis C, Guarnotta C . C1q acts in the tumour microenvironment as a cancer-promoting factor independently of complement activation. Nat Commun. 2016; 7:10346. PMC: 4740357. DOI: 10.1038/ncomms10346. View

Kuijjer M, van den Akker B, Hilhorst R, Mommersteeg M, Buddingh E, Serra M . Kinome and mRNA expression profiling of high-grade osteosarcoma cell lines implies Akt signaling as possible target for therapy. BMC Med Genomics. 2014; 7:4. PMC: 3932036. DOI: 10.1186/1755-8794-7-4. View

Wedekind M, Wagner L, Cripe T . Immunotherapy for osteosarcoma: Where do we go from here?. Pediatr Blood Cancer. 2018; 65(9):e27227. DOI: 10.1002/pbc.27227. View

Ali H, Chlon L, Pharoah P, Markowetz F, Caldas C . Patterns of Immune Infiltration in Breast Cancer and Their Clinical Implications: A Gene-Expression-Based Retrospective Study. PLoS Med. 2016; 13(12):e1002194. PMC: 5154505. DOI: 10.1371/journal.pmed.1002194. View

van Schaarenburg R, Schejbel L, Truedsson L, Topaloglu R, Al-Mayouf S, Riordan A . Marked variability in clinical presentation and outcome of patients with C1q immunodeficiency. J Autoimmun. 2015; 62:39-44. DOI: 10.1016/j.jaut.2015.06.002. View

10.

Langfelder P, Horvath S . WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics. 2008; 9:559. PMC: 2631488. DOI: 10.1186/1471-2105-9-559. View

11.

Kim K, Yi J, Nguyen N, Lee J, Kwon Y, Ahn B . Cell-surface receptor for complement component C1q (gC1qR) is a key regulator for lamellipodia formation and cancer metastasis. J Biol Chem. 2011; 286(26):23093-101. PMC: 3123076. DOI: 10.1074/jbc.M111.233304. View

12.

Kaur A, Sultan S, Murugaiah V, Pathan A, Alhamlan F, Karteris E . Human C1q Induces Apoptosis in an Ovarian Cancer Cell Line Tumor Necrosis Factor Pathway. Front Immunol. 2017; 7:599. PMC: 5174108. DOI: 10.3389/fimmu.2016.00599. View

13.

Hong Q, Sze C, Lin S, Lee M, He R, Schultz L . Complement C1q activates tumor suppressor WWOX to induce apoptosis in prostate cancer cells. PLoS One. 2009; 4(6):e5755. PMC: 2685983. DOI: 10.1371/journal.pone.0005755. View

14.

Holenstein C, Horvath A, Schar B, Schoenenberger A, Bollhalder M, Goedecke N . The relationship between metastatic potential and in vitro mechanical properties of osteosarcoma cells. Mol Biol Cell. 2019; 30(7):887-898. PMC: 6589788. DOI: 10.1091/mbc.E18-08-0545. View

15.

Sim R, Laich A . Serine proteases of the complement system. Biochem Soc Trans. 2000; 28(5):545-50. DOI: 10.1042/bst0280545. View

16.

Zhou Z, Xin H, Li J, Hu Z, Luo C, Zhou S . Intratumoral plasmacytoid dendritic cells as a poor prognostic factor for hepatocellular carcinoma following curative resection. Cancer Immunol Immunother. 2019; 68(8):1223-1233. PMC: 11028119. DOI: 10.1007/s00262-019-02355-3. View

17.

Yu G, Wang L, Han Y, He Q . clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS. 2012; 16(5):284-7. PMC: 3339379. DOI: 10.1089/omi.2011.0118. View

18.

Liu T, Fang X, Ding Z, Sun Z, Sun L, Wang Y . Pre-operative lymphocyte-to-monocyte ratio as a predictor of overall survival in patients suffering from osteosarcoma. FEBS Open Bio. 2015; 5:682-7. PMC: 4556728. DOI: 10.1016/j.fob.2015.08.002. View

19.

Walport M, Davies K, Botto M . C1q and systemic lupus erythematosus. Immunobiology. 1998; 199(2):265-85. DOI: 10.1016/S0171-2985(98)80032-6. View

20.

Chen H, Chong W, Teng C, Yao Y, Wang X, Li X . The immune response-related mutational signatures and driver genes in non-small-cell lung cancer. Cancer Sci. 2019; 110(8):2348-2356. PMC: 6676111. DOI: 10.1111/cas.14113. View