Oral Malign Lezyonlarda STK32C Genindeki Metilasyon ve Ekspresyon Düzeylerinin Araştırılması
Yıl 2025,
Cilt: 4 Sayı: 3, 265 - 271, 30.09.2025
Semra Demokan
,
Seval Turna
,
Comert Sen
,
Kağan Avcı
,
Murat Ulusan
,
Nejat Vakur Olgaç
Öz
Amaç: Demokan ve arkadaşları tarafından yürütülen TÜBİTAK-SBAG-114S497 kodlu proje kapsamında elde edilen array analizleri sonucunda, STK32C geni potansiyel bir epigenetik biyobelirteç adayı olarak belirlenmiştir. Bu çalışmada, oral skuamöz hücreli karsinom (OSCC) olgularından oluşan geniş bir hasta grubunda STK32C geninin metilasyon ve ekspresyon düzeyleri incelenmiş; bu genin erken tanı/prognoz değerlendirme açısından biyobelirteç potansiyeli araştırılmıştır.
Yöntem: 15 OSCC hastasının doku örneklerinden DNA ve RNA izole edilmiş ve STK32C geninin metilasyon ve ekspresyon düzeyleri sırasıyla Kantitatif Metilasyon Spesifik PCR ve Gerçek Zamanlı PCR yöntemleri kullanılarak incelenmiştir.
Bulgular ve Sonuçlar: OSCC hastalarının tümör örneklerinde, STK32C geninin promotör bölgesinde %93,3 metilasyon gözlenmiştir. Ekspresyon seviyeleri değerlendirildiğinde, tümörlü dokulardaki örneklerin %53,3'ünde normal dokulara kıyasla ekspresyon kaybı, %13,3'ünde ise ekspresyon artışı tespit edilmiştir. Ekspresyon seviyeleri düşük olan tüm hastalarda hipermetilasyon saptanmıştır. Hipermetilasyona bağlı STK32C geninde gözlenen ekspresyon kaybının, OSCC hastalarının belirli bir alt grubunun moleküler karakterizasyonunda rol oynayabileceği ve bu genin erken tanı ve prognoz için önemli bir biyobelirteç adayı olabileceği düşünülmektedir. Ancak, bunu doğrulamak için daha geniş hasta popülasyonlarını kapsayan daha fazla çalışmaya ihtiyaç bulunmaktadır.
Proje Numarası
TDP-2020-36656.
Kaynakça
-
Galati, L., Chiocca, S., Duca, D., Tagliabue, M., Simoens, C., Gheit, T., . . . Tommasino, M. (2022). HPV and head and neck cancers: Towards early diagnosis and prevention. Tumour Virus Res, 14, 200245. doi:10.1016/j.tvr.2022.200245
-
Imbesi Bellantoni, M., Picciolo, G., Pirrotta, I., Irrera, N., Vaccaro, M., Vaccaro, F., . . . Pallio, G. (2023). Oral Cavity Squamous Cell Carcinoma: An Update of the Pharmacological Treatment. Biomedicines, 11(4). doi:10.3390/biomedicines11041112
-
Kanwal, R., & Gupta, S. (2012). Epigenetic modifications in cancer. Clin Genet, 81(4), 303-311. doi:10.1111/j.1399-0004.2011.01809.x
-
Li, N., Song, K., Chen, H., & Dai, M. (2025). Advance and challenge of DNA methylation as cancer biomarkers for risk stratification, screening and early detection. J Natl Cancer Cent, 5(2), 108-112. doi:10.1016/j.jncc.2024.12.007
-
Liyanage, C., Wathupola, A., Muraleetharan, S., Perera, K., Punyadeera, C., & Udagama, P. (2019). Promoter Hypermethylation of Tumor-Suppressor Genes p16(INK4a),RASSF1A,TIMP3, and PCQAP/MED15 in Salivary DNA as a Quadruple Biomarker Panel for Early Detection of Oral and Oropharyngeal Cancers. Biomolecules, 9(4). doi:10.3390/biom9040148
-
Moore, L. D., Le, T., & Fan, G. (2013). DNA methylation and its basic function. Neuropsychopharmacology, 38(1), 23-38. doi:10.1038/npp.2012.112
-
Sun, E., Liu, K., Zhao, K., & Wang, L. (2019). Serine/threonine kinase 32C is overexpressed in bladder cancer and contributes to tumor progression. Cancer Biol Ther, 20(3), 307-320. doi:10.1080/15384047.2018.1529098
-
Xiao, H., Liu, L., & Huang, S. (2025). STK32C modulates doxorubicin resistance in triple-negative breast cancer cells via glycolysis regulation. Mol Cell Biochem, 480(1), 459-471. doi:10.1007/s11010-024-04989-z
-
Zhang, C., Cai, Q., & Ke, J. (2023). Poor Prognosis of Oral Squamous Cell Carcinoma Correlates With ITGA6. Int Dent J, 73(2), 178-185. doi:10.1016/j.identj.2022.05.010
-
Zhang, X., Jin, M., Chu, Y., Liu, F., Qu, H., & Chen, C. (2025). STK32C promotes colon tumor progression through activating c-MYC signaling. Cell Mol Life Sci, 82(1), 235. doi:10.1007/s00018-025-05773-y
Investigation of Methylatıon and Expression Levels in STK32C Gene in Oral Malignant Lesions
Yıl 2025,
Cilt: 4 Sayı: 3, 265 - 271, 30.09.2025
Semra Demokan
,
Seval Turna
,
Comert Sen
,
Kağan Avcı
,
Murat Ulusan
,
Nejat Vakur Olgaç
Öz
Aim: As a result of the array analyses obtained within the scope of the TUBITAK-SBAG-114S497 project conducted by Demokan and his colleagues, STK32C gene was determined as a potential epigenetic biomarker candidate. In this study, the methylation and expression levels of STK32C gene were examined in a larger patient group consisting of oral squamous cell carcinoma (OSCC) cases; the biomarker potential of this gene in terms of early diagnosis/prognosis evaluation was investigated.
Method: DNA and RNA were isolated from tissue samples of 15 OSCC patients, and the methylation and expression levels of the STK32C gene were examined using Quantitative Methylation Specific PCR and Real-Time PCR methods, respectively.
Results and Conclusions: In tumor samples of OSCC patients, 93.3% methylation was observed in the promoter region of the STK32C gene. When expression levels were evaluated, expression loss was detected in 53.3% of the samples in tumor tissues compared to normal tissues, while expression increase was observed in 13.3%. Hypermethylation was detected in all patients with decreased expression levels. It is suggested that the loss of expression observed in the STK32C gene due to hypermethylation may play a role in the molecular characterization of a certain subgroup of OSCC patients and that this gene may be a significant biomarker candidate for early diagnosis and prognosis. However, further studies covering larger patient populations are needed to confirm this.
Destekleyen Kurum
This study was supported by Istanbul University Scientific Research Projects Unit with project no. TDP-2020-36656.
Proje Numarası
TDP-2020-36656.
Kaynakça
-
Galati, L., Chiocca, S., Duca, D., Tagliabue, M., Simoens, C., Gheit, T., . . . Tommasino, M. (2022). HPV and head and neck cancers: Towards early diagnosis and prevention. Tumour Virus Res, 14, 200245. doi:10.1016/j.tvr.2022.200245
-
Imbesi Bellantoni, M., Picciolo, G., Pirrotta, I., Irrera, N., Vaccaro, M., Vaccaro, F., . . . Pallio, G. (2023). Oral Cavity Squamous Cell Carcinoma: An Update of the Pharmacological Treatment. Biomedicines, 11(4). doi:10.3390/biomedicines11041112
-
Kanwal, R., & Gupta, S. (2012). Epigenetic modifications in cancer. Clin Genet, 81(4), 303-311. doi:10.1111/j.1399-0004.2011.01809.x
-
Li, N., Song, K., Chen, H., & Dai, M. (2025). Advance and challenge of DNA methylation as cancer biomarkers for risk stratification, screening and early detection. J Natl Cancer Cent, 5(2), 108-112. doi:10.1016/j.jncc.2024.12.007
-
Liyanage, C., Wathupola, A., Muraleetharan, S., Perera, K., Punyadeera, C., & Udagama, P. (2019). Promoter Hypermethylation of Tumor-Suppressor Genes p16(INK4a),RASSF1A,TIMP3, and PCQAP/MED15 in Salivary DNA as a Quadruple Biomarker Panel for Early Detection of Oral and Oropharyngeal Cancers. Biomolecules, 9(4). doi:10.3390/biom9040148
-
Moore, L. D., Le, T., & Fan, G. (2013). DNA methylation and its basic function. Neuropsychopharmacology, 38(1), 23-38. doi:10.1038/npp.2012.112
-
Sun, E., Liu, K., Zhao, K., & Wang, L. (2019). Serine/threonine kinase 32C is overexpressed in bladder cancer and contributes to tumor progression. Cancer Biol Ther, 20(3), 307-320. doi:10.1080/15384047.2018.1529098
-
Xiao, H., Liu, L., & Huang, S. (2025). STK32C modulates doxorubicin resistance in triple-negative breast cancer cells via glycolysis regulation. Mol Cell Biochem, 480(1), 459-471. doi:10.1007/s11010-024-04989-z
-
Zhang, C., Cai, Q., & Ke, J. (2023). Poor Prognosis of Oral Squamous Cell Carcinoma Correlates With ITGA6. Int Dent J, 73(2), 178-185. doi:10.1016/j.identj.2022.05.010
-
Zhang, X., Jin, M., Chu, Y., Liu, F., Qu, H., & Chen, C. (2025). STK32C promotes colon tumor progression through activating c-MYC signaling. Cell Mol Life Sci, 82(1), 235. doi:10.1007/s00018-025-05773-y