CCL2, CCL8, CXCL12 chemokines in resectable non-small cell lung cancer (NSCLC).
ELISA method
NSCLC
biomarker
chemokine CCL2
chemokine CCL8
chemokine CXCL12
peripheral blood
resectability
Journal
Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia
ISSN: 1804-7521
Titre abrégé: Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub
Pays: Czech Republic
ID NLM: 101140142
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
received:
19
07
2022
accepted:
01
12
2022
pubmed:
12
1
2023
medline:
12
1
2023
entrez:
11
1
2023
Statut:
ppublish
Résumé
Complex networks of chemokines are part of the immune reaction targeted against tumor cells. Chemokines influence cancer growth. It is unclear whether the concentrations of chemokines at the time of NSCLC (non-small cell lung cancer) diagnosis differ from healthy controls and reflect the extent of NSCLC. To compare chemokine concentrations (CCL2, CCL8, CXCL12) in the plasma of patients with resectable NSCLC to those without cancer. To determine whether the chemokine concentrations differ relative to the stage of disease. Sixty-nine patients undergoing surgery for proven/suspected NSCLC were enrolled. They underwent standard diagnostic and staging procedures to determine resectability, surgery was performed. Forty-two patients were diagnosed with NSCLC, while 27patients had benign lung lesions and functioned as the control group. Chemokine concentrations in peripheral blood were assessed using ELISA. Parametric statistics were used for the analysis of results. There were no differences in plasma chemokine concentrations in NSCLC patients compared to controls. CXCL12 concentrations correlated positively with tumor extent expressed as clinical stage, (mean values: stage I 5.08 ng/mL, SEM 0.59; stage II and IIIA 7.82 ng/mL; SEM 1.06; P=0.022). Patients with NSCLC stages II+IIIA had significantly higher CXCL12 concentrations than controls (mean values: stage II+IIIA 7.82 ng/mL; SEM 1.06; controls 5.3 ng/mL; SEM 0.46; P=0.017). CXCL12 was related to tumor growth and could potentially be used as a biomarker of advanced disease.
Sections du résumé
BACKGROUND
BACKGROUND
Complex networks of chemokines are part of the immune reaction targeted against tumor cells. Chemokines influence cancer growth. It is unclear whether the concentrations of chemokines at the time of NSCLC (non-small cell lung cancer) diagnosis differ from healthy controls and reflect the extent of NSCLC.
AIMS
OBJECTIVE
To compare chemokine concentrations (CCL2, CCL8, CXCL12) in the plasma of patients with resectable NSCLC to those without cancer. To determine whether the chemokine concentrations differ relative to the stage of disease.
METHODS
METHODS
Sixty-nine patients undergoing surgery for proven/suspected NSCLC were enrolled. They underwent standard diagnostic and staging procedures to determine resectability, surgery was performed. Forty-two patients were diagnosed with NSCLC, while 27patients had benign lung lesions and functioned as the control group. Chemokine concentrations in peripheral blood were assessed using ELISA. Parametric statistics were used for the analysis of results.
RESULTS
RESULTS
There were no differences in plasma chemokine concentrations in NSCLC patients compared to controls. CXCL12 concentrations correlated positively with tumor extent expressed as clinical stage, (mean values: stage I 5.08 ng/mL, SEM 0.59; stage II and IIIA 7.82 ng/mL; SEM 1.06; P=0.022). Patients with NSCLC stages II+IIIA had significantly higher CXCL12 concentrations than controls (mean values: stage II+IIIA 7.82 ng/mL; SEM 1.06; controls 5.3 ng/mL; SEM 0.46; P=0.017).
CONCLUSION
CONCLUSIONS
CXCL12 was related to tumor growth and could potentially be used as a biomarker of advanced disease.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
335-339Déclaration de conflit d'intérêts
The authors report no conflicts of interest in this work.
Références
Havel L. Present Experience and Perspectives of Immunotherapy of Lung Cancer, Klin Onkol 2015;28(4):73-6. (In Czech)
doi: 10.14735/amko20154S73
Fridman WH, Pages F, Sautes-Fridman C, Galon J. The immune contexture in human tumours: impact on clinical outcome. Nat Rev Cancer 2012;12:298-306.
doi: 10.1038/nrc3245
Bremnes RM, Al-Shibli K, Donnem T, Sirera R, Al-Saad S, Andersen S, Stenvold H, Camps C, Busund LT. The role of tumor-infiltrating immune cells and chronic inflammation at the tumor site on cancer development, progression, and prognosis: emphasis on non-small cell lung cancer. J Thorac Oncol 2011;6(4):824-33.
doi: 10.1097/JTO.0b013e3182037b76
Rivas-Fuentes S, Salgado-Aguayo A, Pertuz Belloso S, Gorocica Rosete P, Alvarado-Vásquez N, Aquino-Jarquin G. Role of Chemokines in Non-Small Cell Lung Cancer: Angiogenesis and Inflammation. J Cancer 2015;6(10):938-52.
doi: 10.7150/jca.12286
Kudo-Saito C, Shirako H, Ohike M, Tsukamoto N, Kawakami Y. CCL2 is critical for immunosuppression to promote cancer metastasis. Clin Exp Metastasis 2013;30(4):393-405.
doi: 10.1007/s10585-012-9545-6
CCL8 C-C motif chemokine ligand 8 [Homo sapiens (human)] - Gene - NCBI. (n.d.). Retrieved June 18, 2017. Available from https://www.ncbi.nlm.nih.gov/gene/6355
Wald O, Shapira O, Uzi Izhar U. CXCR4/CXCL12 Axis in Non Small Cell Lung Cancer (NSCLC) Pathologic Roles and Therapeutic Potential. Theranostics 2013;3(1):26-33.
doi: 10.7150/thno.4922
Cheng ZH, Shi YX, Yuan M, Xiong D, Zheng JH, Zhang ZY. Chemokines and their receptors in lung cancer progression and metastasis. J Zhejiang Univ Sci B 2016;17(5):342-51.
doi: 10.1631/jzus.B1500258
Postmus PE, Kerr KM, Oudkerk M, Senan S, Waller DA, Vansteenkiste J, Escriu C, Peters S; ESMO Guidelines Committee. Early and locally advanced non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 20171;28(suppl_4):iv1-iv21.
doi: 10.1093/annonc/mdx222
Detterbeck FC, Boffa DJ, Kim AW, Tanoue LT. The Eighth Edition Lung Cancer Stage Classification. Chest 2017;151:193-203.
doi: 10.1016/j.chest.2016.10.010
Stamatovic SM, Keep RF, Mostarica-Stojkovic M, Andjelkovic AV. CCL2 regulates angiogenesis via activation of Ets-1 transcription factor. J Immunol 2006;177(4):2651-61.
doi: 10.4049/jimmunol.177.4.2651
Salcedo R, Ponce ML, Young HA, Wasserman K, Ward JM, Kleinman HK, Oppenheim JJ, Murphy WJ. Human endothelial cells express CCR2 and respond to MCP-1: direct role of MCP-1 in angiogenesis and tumor progression. Blood 2000;96:34-40.
doi: 10.1182/blood.V96.1.34
Farmaki E, Chatzistamou I, Vimala Kaza V, Hippokratis Kiaris H. A CCL8 gradient drives breast cancer cell dissemination. Oncogene 2016;35(49):6309-631.
doi: 10.1038/onc.2016.161
Wald O, Izhar U, Amir G, Avniel S, Bar-Shavit Y, Wald H, Weiss ID, Galun E, Peled A. CD4+CXCR4 high CD69+ T cells accumulate in lung adenocarcinoma. J Immunol 2006;177:6983-90.
doi: 10.4049/jimmunol.177.10.6983
Burger JA, Stewart DJ, Wald O, Peled A. Potential of CXCR4 antagonists for the treatment of metastatic lung cancer. Expert Rev Anticancer Ther 2011;11(4):621-30.
doi: 10.1586/era.11.11
Domingo-Gonzalez R, Prince O, Cooper A, Khader SA. Cytokines and Chemokines in Mycobacterium tuberculosis Infection. Microbiol Spectr 2016;4(5):10.
doi: 10.1128/microbiolspec.TBTB2-0018-2016
Proost P1, Wuyts A, van Damme J. The role of chemokines in inflammation. Int J Clin Lab Res 1996;26(4):211-23.
Spaks A. Role of CXC group chemokines in lung cancer development and progression. J Thorac Dis 2017;9(Suppl 3):S164-S17.
doi: 10.21037/jtd.2017.03.61
Zhang XW, Qin X, Qin CY, Yin YL, Chen Y, Zhu HL. Expression of monocyte hemoattractant protein-1 and CC chemokine receptor 2 in non-small cell lung cancer and its significance. Cancer Immunol Immunother 2013;62(3):563-70.
doi: 10.1007/s00262-012-1361-y
Miotto D, Boschetto P, Bononi I, Milani G, Legorini C, Cavallesco G, Lo Cascio N, Zeni E, Fabbri LM, Mapp CE. CC ligand 2 levels are increased in LPS-stimulated peripheral monocytes of patients with non-small cell lung cancer. Respir Med 2007;101(8):1738-43.
doi: 10.1016/j.rmed.2007.02.021
Cassetta L, Fragkogianni S, Sims AH, Swierczak A, Forrester LM, Zhang H, Soong DYH, Cotechini T, Anur P, Lin EY, Fidanza A, Lopez-Yrigoyen M, Millar MR, Urman A, Ai Z, Spellman PT, Hwang ES, Dixon JM, Wiechmann L, Coussens LM, Smith HO, Pollard JW. Human Tumor-Associated Macrophage and Monocyte Transcriptional Landscapes Reveal Cancer-Specific Reprogramming, Biomarkers, and Therapeutic Targets. Cancer Cell 2019;35(4):588-602.
doi: 10.1016/j.ccell.2019.02.009
Hu T, Yao Y, Yu S, Guo H, Tian T, Han L, Wang W, Guo Q, Wang J, Nan K, Wang S. CXCR4 and Nrf2 expressions in non-small cell lung cancer and their clinical implications. J South Med Univ 2014;34(2):153-8.
Wald O. CXCR4 Based Therapeutics for Non-Small Cell Lung Cancer (NSCLC). J Clin Med 2018;7(10):303. doi: 10.3390/jcm7100303
pubmed: 30257500
doi: 10.3390/jcm7100303