Dioken Didem Naz, Ozgul Ibrahim, Koksal Bicakci Gozde, Gol Kemal, Can Tolga, Erson-Bensan Ayse Elif
Department of Biological Sciences, Middle East Technical University (METU), Dumlupinar Blv No: 1 Universiteler Mah., Cankaya, Ankara, 06800, Turkiye.
Gynecology Clinic, Ugur Mumcu Cad 17/2, Cankaya, Ankara, Turkiye.
Heliyon. 2023 Sep 9;9(9):e20035. doi: 10.1016/j.heliyon.2023.e20035. eCollection 2023 Sep.
Early diagnosis and therapeutic targeting are continuing challenges for gynecological cancers. Here, we focus on cancer transcriptomes and describe the differential expression of 3'UTR isoforms in patients using an algorithm to detect differential poly(A) site usage. We find primarily 3'UTR shortening cases in cervical cancers compared with the normal cervix. We show differential expression of alternate 3'-end isoforms of , , and in HPV16-positive patients who develop high-grade cervical lesions compared with the infected but non-progressing group. In contrast, in ovarian cancers, 3'UTR lengthening is more evident compared with normal ovary tissue. Nevertheless, highly malignant ovarian tumors have unique 3'UTR shortening events (e.g., , and some of which correlate with upregulated protein levels in tumors. Overall, our study shows isoform level deregulation in gynecological cancers and highlights the complexity of the transcriptome. This transcript diversity could help identify novel cancer genes and provide new possibilities for diagnosis and therapy.
早期诊断和靶向治疗仍然是妇科癌症面临的挑战。在此，我们聚焦于癌症转录组，并使用一种算法检测差异多聚腺苷酸化位点的使用情况，描述患者中3'UTR异构体的差异表达。我们发现，与正常宫颈相比，宫颈癌中主要是3'UTR缩短的情况。我们显示，与感染但未进展的组相比，在发生高级别宫颈病变的HPV16阳性患者中，、和的可变3'端异构体存在差异表达。相比之下，在卵巢癌中，与正常卵巢组织相比，3'UTR延长更为明显。然而，高恶性卵巢肿瘤有独特的3'UTR缩短事件（例如，和，其中一些与肿瘤中上调的蛋白质水平相关。总体而言，我们的研究显示了妇科癌症中异构体水平的失调，并突出了转录组的复杂性。这种转录本多样性有助于识别新的癌症基因，并为诊断和治疗提供新的可能性。
