Şule TERZİOĞLU UŞAK, Cem HOROZOĞLU, Şeyda DEMİRKOL, Akif TURNA, İlhan YAYLIM

The role of galectin-3 and its genetic variants in tumor risk and survival of patients with surgically resected early-stage non-small cell lung cancer

Background: The aim of this study was to investigate the possible relationship between galectin-3 gene variants, serum level, gene expression level, and the risks and survivals of resectable non-small cell lung cancer patients. Methods: The rs4644 and rs4652 variants of galectin-3 were genotyped by TaqMan single nucleotide polymorphism assay using genomic deoxyribonucleic acid isolated from the peripheral blood of 65 (54 males, 11 females; mean age: 60.1±11.9 years; range, 34 to 83 years) with Stage IA-IIIA non-small cell lung cancer who underwent primary surgical treatment and 95 healthy individuals (48 males, 47 females; mean age: 53.9±13.5 years; range, 32 to 87 years) between March 2017 and September 2018. Circulating galectin-3 levels in serum samples of the patient and control groups were assessed by enzyme-linked immunosorbent assay. Messenger ribonucleic acid expression of galectin-3 in tumor and surrounding tissues of the patient group was examined by real-time quantitative polymerase chain reaction. Both predictive and prognostic significance of the results were analyzed. Results: The presence of angiolymphatic invasion was significant in the patients with rs4652 AA genotype (p=0.04). Serum galectin-3 levels were significantly higher in the patients than the controls (p

Cerrahi rezeksiyon uygulanmış erken evre küçük hücreli dışı akciğer kanserli hastalarda galektin-3 ve genetik varyantlarının tümör riski ve sağkalım üzerindeki rolü

Amaç: Bu çalışmada galektin-3 gen varyantları, serum düzeyi, gen ekspresyon düzeyi ile rezektabl küçük hücreli dışı akciğer kanseri hastalarının riskleri ve sağkalımları arasındaki olası ilişki araştırıldı. Çalışma planı: Mart 2017 - Eylül 2018 tarihleri arasında galektin-3'ün rs4644 ve rs4652 varyantları, primer cerrahi tedavi yapılan küçük hücreli dışı akciğer kanserli 65 hastanın (54 erkek, 11 kadın; ort. yaş: 60.1±11.9 yıl; dağılım, 34-83 yıl) ve 95 sağlıklı bireyin (48 erkek, 47 kadın; ort. y aş: 53.9±13.5 y ıl; d ağılım, 32-87 y ıl) p eriferik k anından i zole e dilen genomik deoksiribonükleik asitler kullanılarak TaqMan tek nükleotid polimorfizm testi ile genotiplendi. Hasta ve kontrol gruplarının serum örneklerinde dolaşımdaki galektin-3 düzeyi, enzim bağlı immünosorbent testi ile değerlendirildi. Hasta grubunda tümör ve çevre dokulardaki galektin-3’ün haberci ribonükleik asit ekspresyonu, gerçek zamanlı kantitatif polimeraz zincir reaksiyonu ile incelendi. Bu sonuçların hem prediktif, hem de prognostik önemi analiz edildi. Bulgular: Rs4652 AA genotipi olan hastalarda anjiyolenfatik invazyon varlığı anlamlı idi (p=0.04). Kontrol grubuna kıyasla, hastalarda serum galektin-3 düzeyleri anlamlı düzeyde yüksekti (p

PDF

___

1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin 2019;69:7-34.
2. Goldstraw P, Crowley J, Chansky K, Giroux DJ, Groome PA, Rami-Porta R, et al. The IASLC Lung Cancer Staging Project: Proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM classification of malignant tumours. J Thorac Oncol 2007;2:706-14.
3. Liao Z, Lin SH, Cox JD. Status of particle therapy for lung cancer. Acta Oncol 2011;50:745-56.
4. Detterbeck FC, Boffa DJ, Tanoue LT. The new lung cancer staging system. Chest 2009;136:260-71.
5. Chang A. Chemotherapy, chemoresistance and the changing treatment landscape for NSCLC. Lung Cancer 2011;71:3-10.
6. Kadrofske MM, Openo KP, Wang JL. The human LGALS3 (galectin-3) gene: Determination of the gene structure and functional characterization of the promoter. Arch Biochem Biophys 1998;349:7-20.
7. Liu FT, Rabinovich GA. Galectins as modulators of tumour progression. Nat Rev Cancer 2005;5:29-41.
8. Markowska AI, Liu FT, Panjwani N. Galectin-3 is an important mediator of VEGF- and bFGF-mediated angiogenic response. J Exp Med 2010;207:1981-93.
9. Takenaka Y, Fukumori T, Raz A. Galectin-3 and metastasis. Glycoconj J 2002;19:543-9.
10. Saussez S, Lorfevre F, Lequeux T, Laurent G, Chantrain G, Vertongen F, et al. The determination of the levels of circulating galectin-1 and -3 in HNSCC patients could be used to monitor tumor progression and/or responses to therapy. Oral Oncol 2008;44:86-93.
11. Chung LY, Tang SJ, Wu YC, Sun GH, Liu HY, Sun KH. Galectin-3 augments tumor initiating property and tumorigenicity of lung cancer through interaction with β-catenin. Oncotarget 2015;6:4936-52.
12. Hu CY, Chang SK, Wu CS, Tsai WI, Hsu PN. Galectin-3 gene (LGALS3) +292C allele is a genetic predisposition factor for rheumatoid arthritis in Taiwan. Clin Rheumatol 2011;30:1227-33.
13. Balan V, Nangia-Makker P, Schwartz AG, Jung YS, Tait L, Hogan V, et al. Racial disparity in breast cancer and functional germ line mutation in galectin-3 (rs4644): A pilot study. Cancer Res 2008;68:10045-50.
14. Meyer A, Coinac I, Bogdanova N, Dubrowinskaja N, Turmanov N, Haubold S, et al. Apoptosis gene polymorphisms and risk of prostate cancer: A hospital-based study of German patients treated with brachytherapy. Urol Oncol 2013;31:74-81.
15. Chen HJ, Zheng ZC, Yuan BQ, Liu Z, Jing J, Wang SS. The effect of galectin-3 genetic variants on the susceptibility and prognosis of gliomas in a Chinese population. Neurosci Lett 2012;518:1-4.
16. Shi Y, Lin X, Chen G, Yan J, Ying M, Zheng X. Galectin-3 rs4652 A>C polymorphism is associated with the risk of gastric carcinoma and P-glycoprotein expression level. Oncol Lett 2017;14:8144-9.
17. Fang SQ, Feng YM, Li M. Correlations of galectin-3 gene polymorphisms with risk and prognosis of cervical cancer in Chinese populations: A case-control study. Oncol Res Treat 2017;40:533-9.
18. Groome PA, Bolejack V, Crowley JJ, Kennedy C, Krasnik M, Sobin LH, et al. The IASLC Lung Cancer Staging Project: validation of the proposals for revision of the T, N, and M descriptors and consequent stage groupings in the forthcoming (seventh) edition of the TNM classification of malignant tumours. J Thorac Oncol 2007;2:694-705.
19. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988;16:1215.
20. Akobeng AK. Understanding diagnostic tests 3: Receiver operating characteristic curves. Acta Paediatr 2007;96:644-7.
21. Kacan M, Turkyilmaz M, Karabulut F, Altun O, Baran Y. Complexation, thermal and catalytic studies of N-substituted piperazine, morpholine and thiomorpholine with some metal ions. Spectrochim Acta A Mol Biomol Spectrosc 2014;118:572-7.
22. Wu F, Hu N, Li Y, Bian B, Xu G, Zheng Y. Galectin-3 genetic variants are associated with platinum-based chemotherapy response and prognosis in patients with NSCLC. Cell Oncol (Dordr) 2012;35:175-80.
23. Sung SY, Kwak YK, Lee SW, Jo IY, Park JK, Kim KS, et al. Lymphovascular invasion increases the risk of nodal and distant recurrence in node-negative stage I-IIA non-smallcell lung cancer. Oncology 2018;95:156-62.
24. Kaur T, Sodhi A, Singh J, Arora S, Kamboj SS, Kaur M. Evaluation of galectin-3 genetic variants and its serum levels in rheumatoid arthritis in North India. International Journal of Human Genetics 2015;15:131-8.
25. Menon RP, Hughes RC. Determinants in the N-terminal domains of galectin-3 for secretion by a novel pathway circumventing the endoplasmic reticulum-Golgi complex. Eur J Biochem 1999;264:569-76.
26. Webber JP, Spary LK, Sanders AJ, Chowdhury R, Jiang WG, Steadman R, et al. Differentiation of tumour-promoting stromal myofibroblasts by cancer exosomes. Oncogene 2015;34:290-302.
27. Bach PB, Kattan MW, Thornquist MD, Kris MG, Tate RC, Barnett MJ, et al. Variations in lung cancer risk among smokers. J Natl Cancer Inst 2003;95:470-8.
28. Kataoka Y, Igarashi T, Ohshio Y, Fujita T, Hanaoka J. Predictive importance of galectin-3 for recurrence of non-small cell lung cancer. Gen Thorac Cardiovasc Surg 2019;67:704-11.