Changes in glycocalyx-related biochemical parameters during lung resection in non-small cell carcinoma cases : A pilot study

Main Article Content

Salih Cokpinar
Selda Sen
Imran Kurt Omurlu
Aslihan Karul
Sinem Sari
Serdar Sen


Objective: Non-small cell lung cancer (NSCLC) is one of the most common neoplasms with high mortality rates, and new studies are needed to understand its characteristics better. This study aimed to determine the changes in the glycocalyx structure related to surgery regarding histopathologic subtypes and to evaluate the correlation of these changes on the development of metastasis and mortality.

Material and methods: Serum levels of hyaluronan, VEGF-A, FGF-10, BMP-2, and BMP-4 were measured before and after surgery in 42 patients with NSCLC. The alterations in serum levels of studied markers were evaluated as related to metastasis status and mortality in post-operative 18-24 months.

Results: Our study included 15 adenocarcinoma and 27 squamous cell carcinoma cases. Pre- and post-operative values of serum hyaluronan, VEGF-A, FGF-10, and BMP-2 showed significant differences for the whole group (p=0.006, p=0.001, p=0.002, and p=0.004, respectively). Post-operative BMP-2 values also correlated with hyaluronan and VEGF-A values. Post-operative values of hyaluronan and VEGF-A values found incorrelation with metastasis and mortality, while BMP-2 with metastasis and FGF-10 with mortality. Serum values of hyaluronan, VEGF-A, FGF-10 and BMP-2 differed significantly in-between the pre- and post-operative measurements in adenocarcinoma cases (p=0.020, p=0.009, p=0.003, and p=0.011, respectively) , but not that of squamous cell carcinoma.

Conclusion: Pre- and post-operative changes in serum hyaluronan, VEGF-A, FGF-10 and BMP-2 values may be associated with metastasis and/or mortality in NSCLC. These findings were also more prominent in adenocarcinoma cases, though further extended studies are needed for a better conclusion.


Download data is not yet available.

Article Details

How to Cite
Cokpinar, S., Sen, S., Omurlu, I. K. ., Karul, A. ., Sari, S., & Sen, S. (2022). Changes in glycocalyx-related biochemical parameters during lung resection in non-small cell carcinoma cases : A pilot study. Medical Science and Discovery, 9(10), 558–565.
Research Article
Received 2022-09-11
Accepted 2022-10-21
Published 2022-10-21


Torre LA, Siegel RL and Jemal A: Lung cancer statistics. Adv Exp Med Biol 2016, 893: 1‑19. DOI:

Puderecki M, Szumıło J and Marzec‑kotarska B. Novel prognostic molecular markers in lung cancer (Review) Oncology Letters 2020, 20: 9-18. DOI:10.3892/ol.2020.11541 DOI:

Curry FE, Adamson RH. Endothelial glycocalyx: permeability barrier and mechanosensor. Ann Biomed Eng. 2012 ; 40(4): 828–839. doi:10.1007/s10439-011-0429-8. DOI:

Rangel MP, de Sá VK, Martins V, Martins JRM, Parra ER, Mendes A, et al. Tissue hyaluronan expression, as reflected in the sputum of lung cancer patients, is an indicator of malignancy. Braz J Med Biol Res. 2015;48(6):557-67. doi: 10.1590/1414-431X20144300. DOI:

Clayton NS , Grose RP. Emerging Roles of Fibroblast Growth Factor 10 in Cancer Front. Genet.,2018;9: | DOI:

Frezzetti D, Gallo M, Maiello MR, D'Alessio A, Esposito C, Chicchinelli N, Normanno N, De Luca A.VEGF as a potential target in lung cancer. Expert Opin Ther Targets. 2017;21(10):959-966. doi: 10.1080/14728222.2017.1371137. DOI:

Bieniasz M, Oszajca K, Eusebio M, Kordiak J, Bartkowiak J, Szemraj J. The positive correlation between gene expression of the two angiogenic factors: VEGF and BMP-2 in lung cancer patients. Lung Cancer. 2009; 66(3):319-26. doi:10.1016/j.lungcan. 2009. 02.020 DOI:

Astapenko D, Benes J, Pouska J, Lehmann C, Islam S, Cerny V. Endothelial glycocalyx in acute care surgery - what anaesthesiologists need to know for clinical practice. BMC Anesthesiol. 2019 ;19(1):238. doi: 10.1186/s12871-019-0896-2. DOI:

Arthur A, McCall PJ, Jolly L, Kinsalla J, Kirk A, Shelley B. Endothelial glycocalyx layer shedding following lung resection. Biomarkers in Medicine 2016; 10(10): 1033-1038. DOI: 10.2217/bmm-2016-0163. DOI:

Lung. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. Springer; 2017, pp. 431–56. DOI:

Tarbell JM and Cancel LM. The glycocalyx and its significance in human medicine. J Intern Med 2016; 280: 97–113. doi: 10.1111/joim.12465 DOI:

Wang J, Wu A, Wu Y. Endothelial glycocalyx layer: a possible therapeutic target for acute lung injury during lung resection. Biomed Res Int. 2017;2017:5969657. doi: 10.1155/2017/5969657. DOI:

Liu M, Tolg C,Turley E. Dissecting the Dual Nature of Hyaluronan in the Tumor Microenvironment. Front Immunol. 2019; 10: 947. doi: 10.3389/fimmu.2019.00947. DOI:

Caon I, Bartolini I, Parnigoni A, Caravà E, Moretto P, Viola M, et al Revisiting the hallmarks of cancer: The role of hyaluronan. Seminars in Cancer Biology 2020;62 :9-19. DOI:

Anttila MA, Tammi RH, Tammi MI, Syrjanen KJ, Saarikoski S, Kosma VM. High levels of stromal hyaluronan predict poor disease outcome in epithelial ovarian cancer. Cancer Res 2000;60:150–5.

Ropponen K, Tammi M, Parkkinen J, Eskelinen M, Tammi R, Lipponen P, et al. Tumor cell-associated hyaluronan as an unfavorable prognostic factor in colorectal cancer. Cancer Res 1998;58:342–7.

Pirinen R, Tammi R, Tammi M, Hirvikoski P, Parkkinen JJ, Johansson R, et al. Prognostic value of hyaluronan expression in non-small-cell lung cancer: Increased stromal expression indicates unfavorable outcome in patients with adenocarcinoma. Int J Cancer . 2001 ;95(1):12-7. doi: 10.1002/1097-0215(20010120)95. DOI:<12::AID-IJC1002>3.0.CO;2-E

Gong J, Guan M , Galen CW, Larson BK, Zhou J, Patel R, et al. Tumor hyaluronan (HA) as a novel biomarker in non-small cell lung cancer (NSCLC). Journal of Clinical Oncology 2018; 36:e24280. DOI: 10.1200/JCO.2018.36.15_suppl.e24280 DOI:

Tammela T, Enholm B, Alitalo K, Paavonen K: The biology of vascular endothelial growth factors. Cardiovasc Res 2005, 65:550-563. DOI:

Claesson-Welsh L, Welsh M.. VEGFA and tumour angiogenesis . J Intern Med 2013; 273: 114–127. doi: 10.1111/joim.12019 DOI:

Zhan P, Wang J, Lv XJ, Wang Q, Qiu LX, Lin XQ, et al..Prognostic value of vascular endothelial growth factor expression in patients with lung cancer: a systematic review with meta-analysis. J Thorac Oncol. 2009;4(9):1094-103. doi: 10.1097/JTO. 0b013 e3 181a97e31. DOI:

Ng CS, Wan S, Wong RH, Ho AM, Yim AP. Angiogenic response to major lung resection for non-small cell lung cancer with video-assisted thoracic surgical and open access. Scientific World Journal. 2012;2012:636754. doi: 10.1100/2012/636754. DOI:

Xie Y, Su N, Yang J, Tan Q, Huang S, Jin M, et al. FGF/FGFR signaling in health and disease Signal Transduct Target Ther. 2020 ;5(1):181. doi: 10.1038/s41392-020-00222-7. DOI:

Fang, X., Bai, C. & Wang, X. Potential clinical application of KGF-2 (FGF-10) for

acute lung injury/acute respiratory distress syndrome. Expert Rev. Clin. Pharm.2010; 3:797–805. DOI:

De Vinuesa AG, Abdelilah-Seyfried S, Knaus P, Zwijsen A, Bailly S. BMP signaling in vascular biology and dysfunction Cytokine Growth Factor Rev. 2016 ;27:65-79. doi: 10.1016/j.cytogfr.2015.12.005. DOI: