Serum transforming growth factor-beta levels and severity of retinoblastoma in children

M Farid Huzein; Nadirah Rasyid Ridha; Dasril Daud

doi:10.14238/pi63.3.2023.169-72

M Farid Huzein
Nadirah Rasyid Ridha
Dasril Daud

DOI: https://doi.org/10.14238/pi63.3.2023.169-72

Keywords: TGF-Î² levels, Severity, Grade III Retinoblastoma, Grade IV Retinoblastoma

Abstract

Background Transforming growth factor-? (TGF-?) expression contributes to the growth of retinoblastoma. TGF-? is produced or released by infiltrating cells such as lymphocytes and monocytes/macrophages. TGF-? levels are a potential marker of disease severity.

Objective To assess the difference in serum TGF-? levels before chemotherapy in patients with retinoblastoma grades III and IV.

Methods This cross-sectional observational study was done at Dr. Wahidin Sudirohusodo Hospital, Makassar, Indonesia from January to November 2019. Subjects were pediatric patients with grade III and IV retinoblastoma who had not undergone chemotherapy. Patients who met the inclusion criteria provided blood specimens for TGF-? testing. We analyzed the difference in serum TGF-? level between grade III and grade IV patients.

Results We obtained 38 subjects, consisting of 13 grade III and 25 grade IV retinoblastoma patients. Mean TGF-? levels were in 1,061 ng/L in grade III and 988 ng/L in grade IV patients. The Mann-Whitney U test revealed no significant difference between the levels of TGF-?, retinoblastoma grade III and IV (P=0.655). However, TGF-? levels in both groups were markedly above the normal value (100 ng/L).

Conclusion TGF-? levels are markedly increased in grade III and IV retinoblastoma patients. There was no significant difference in TGF-? level between grade III and IV patients. Our findings suggest that TGF-? plays an important role in tumor cell development. Further research on differences in TGF-? levels between late stages (grades III and IV) and early stages (grades I and II) of retinoblastoma to elucidate the role of TGF-? as a marker of retinoblastoma severity.

References

Stacey AW, Bowman R, Foster A, Kivelä TT, Munier FL, Cassoux N, et al. Incidence of retinoblastoma has increased: results from 40 European countries. Ophthalmology. 2021;128:1369–71. DOI : https://doi.org/10.1016/j.ophtha.2021.01.024.
2. Meel R, Radhakrishnan V, Bakhshi S. Current therapy and recent advances in the management of retinoblastoma. Indian J Med Paediatr Oncol. 2012;33:80–8. DOI: https://doi.org/10.4103/0971-5851.99731
3. Dharmawidiarini D, Prijanto, Soebagjo HD. Ocular survival rate penderita retinoblastoma yang telah dilakukan enukleasi atau eksenterasi di RSUD Dr. Soetomo Surabaya. Jurnal Oftalmologi Indonesia (JOI). 2010;7: 94-102. ISSN 1693-2587.
4. Paddupai S. Prevalensi penderita retinoblastoma di RS. Wahidin Sudirohusodo Tahun 2005-2010. [cited 15 October 2022]. Available from: http://repository.unhas.ac.id.
5. Wu XJ, Zeng Y, Wu S, Zhong JX, Wang YZ, Xu JF. MiR-204, down-regulated in retinoblastoma, regulates proliferation and invasion of human retinoblastoma cells by targeting CyclinD2 and MMP-9. FEBS Lett. 2015;589:645–50. DOI: https://doi.org/10.1016/j.febslet.2015.01.030.
6. Derynck, R., Akhurst, RJ, Balmain, A. 2001. TGF-? signaling in tumor suppression and cancer progression. Nature Genetics. 2001;29:117-29. DOI: https://doi.org/10.1038/ng1001-117.
7. Grainger DJ, Mosedale DE, Metcalfe JC. TGF-? in blood: a complex problem. Cytokine & Growth Factor Reviews. 2000;11:133-45. DOI: https://doi.org/10.1016/S1359-6101(99)00037-4.
8. Shehata HH, Ghalia AHA, Elsayed EK, Said AMA, Mahmoud SS. Clinical significance of high levels of survivin and transforming growth factor beta-1 proteins in aqueous humor and serum of retinoblastoma patients. J AAPOS. 2016;20:444.e1-9. DOI: https://doi.org/10.1016/j.jaapos.2016.07.223.
9. Nafianti S. Retinoblastoma in Children in Haji Adam Malik Hospital Medan. Majalah Kedokteran Nusantara- Journal of Medical School. 2006;39:147-50.
10. Rosdiana N. Gambaran klinis dan laboratorium retinoblastoma. Sari Pediatri. 2011;12: 319-22. DOI: https://doi.org/10.14238/sp12.5.2011.319-22.
11. Taba JAP, Ernst C. Retinoblastoma unilateral: sebuah laporan kasus pada pelayanan kesehatan sekunder dengan fasilitas terbatas. Intisari Sains Medis. 2020;11:540-5. DOI: https://doi.org/10.15562/ism.v11i2.669.
12. Baersch G, Baumann M, Ritter J, Jürgens H, Vormoor J. Expression of AC133 and CD117 on candidate normal stem cell populations in childhood B-cell precursor acute lymphoblastic leukaemia. Br J Haematol. 1999;107:572–80. DOI: https://doi.org/10.1046/j.1365-2141.1999.01746.
13. Sun J, Xi HY, Shao Q, Liu QH. Biomarkers in retinoblastoma. Int J Ophthalmol. 2020;13:325–41. DOI: https://doi.org/10.18240/ijo.2020.02.18.