THE CLINICAL SIGNIFICANCE OF SOX9 GENE IN DIFFERENT CANCER TYPES:AN IN-SILICO ANALYSIS

Year 2024, , 63 - 73, 30.07.2024

Ethem Serhat Yavaş , Sedef Hande Aktaş , Göksel Efendioğlu , Dilara Fatma Akın

https://doi.org/10.18036/estubtdc.1312624

Abstract

One of the common problems in the pathogenesis of human cancer is characterized as the dysregulation of transcription factors. SOX9 is important as it is one of the critical transcription factors involved in various diseases, including cancer. In addition, SOX9 also acts as a proto-oncogene or tumor suppressor gene, depending on the cancer type. In this study, we aimed to reveal the mutation and expression status of the SOX9 transcription factor and the effect of this gene on the survival of patients with different cancer groups. The data sets for expression analysis and overall survival analysis were performed by the GEPIA database. Analysis of the mutation profile was performed by the cBio database. As a result, SOX9 gene expressions were significantly elevated in BLCA, CESC, CHOL, COAD, ESCA, GBM, KIRP, LGG, LIHC, LUSC, OV, PAAD, READ, SKCM, STAD, TGCT, THYM, UCEC and UCS in cancer tissues compared to that in normal tissues (p<0.05). According to overall survival (OS) analysis; the SOX9 gene has a significant relationship with OS in ACC, CESC, KIRC, LGG, and THYM (ACC p:0.0079, CESC p:0.038, KIRC p:0.051, LGG p:0.00055, THYM p:0.031). A total of 170 mutations in SOX9 were determined according to mutation analysis. Seventy-six of them were detected as driver mutations. The analysis shows that SOX9 expression status has a different effect in each cancer type, and although there is no significant mutation in the SOX9 gene in ACC cancer type, high expression of this gene is important for survival. Therefore, it is of great importance to analyze the epigenetic changes in the SOX9 gene in ACC cancer type. The analysis also indicates that the SOX9 gene is discriminatory for the survival of adrenocortical carcinoma, cervical squamous cell carcinoma and endocervical adenocarcinoma, renal clear cell carcinoma, brain low-grade glioma and thymoma cancer types.

Keywords

SOX9, Transcription factor, Tumorigenesis, Mutation, Gene expression

THE CLINICAL SIGNIFICANCE OF SOX9 GENE IN DIFFERENT CANCER TYPES:AN IN-SILICO ANALYSIS

Abstract

İnsan kanserinin patogenezindeki yaygın sorunlardan biri, transkripsiyon faktörlerinin düzensizliği olarak karakterize edilir. SOX9, kanser de dahil olmak üzere çeşitli hastalıklarda rol oynayan kritik transkripsiyon faktörlerinden biri olduğu için önemlidir. Ayrıca SOX9, kanser türüne bağlı olarak bir proto-onkogen veya tümör baskılayıcı gen olarak da görev yapar. Bu çalışmada, SOX9 transkripsiyon faktörünün mutasyon ve ekspresyon durumunu ve bu genin farklı kanser türüne sahip hasta gruplarında sağ kalım üzerindeki etkisini ortaya koymayı amaçladık. Ekspresyon analizi ve genel sağ kalım analizi için veri setleri GEPIA veri tabanı üzerinden gerçekleştirilmiştir. Mutasyon profilinin analizi cBio veri tabanı üzerinden gerçekleştirilmiştir. Sonuç olarak, SOX9 gen ekspresyonları BLCA, CESC, CHOL, COAD, ESCA, GBM, KIRP, LGG, LIHC, LUSC, OV, PAAD, READ, SKCM, STAD, TGCT, THYM, UCEC ve UCS kanser dokularında normal dokulardakine kıyasla önemli ölçüde artmıştır (p<0.05). Genel sağ kalım (OS) analizine göre; SOX9 geni ACC, CESC, KIRC, LGG ve THYM'de OS ile anlamlı bir ilişkiye sahiptir (ACC p:0.0079, CESC p:0.038, KIRC p:0.051, LGG p:0.00055, THYM p:0.031). Mutasyon analizine göre SOX9'da toplam 170 mutasyon tespit edilmiştir. Bunlardan yetmiş altısı sürücü mutasyon olarak tespit edilmiştir. Gerçekleştirilen analizler SOX9 ekspresyon durumunun her kanser türünde farklı etkiye sahip olduğunu, ACC kanser türünde SOX9 geninde önemli bir mutasyon bulunmamasına rağmen bu genin yüksek ekspresyonunun sağkalım açısından önemli olduğunu göstermektedir. Bu nedenle, ACC kanser türünde SOX9 genindeki epigenetik değişikliklerin de analiz edilmesi büyük önem taşımaktadır. Analiz ayrıca SOX9 geninin adrenokortikal karsinom, servikal skuamöz hücreli karsinom ve endoservikal adenokarsinom, böbrek renal berrak hücreli karsinom, beyin düşük dereceli gliom ve timoma kanser türlerinin sağkalımı için ayırt edici olduğuna işaret etmektedir.

Keywords

SOX9, Transkripsiyon faktörü, gen ifadesi, mutasyon, sağkalım

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