the Fifth Congress of the Serbian Association for Cancer Research (SDIR) with international participation “Translational potential of cancer research in Serbia”, Belgrade, Sırbistan, 03 Aralık 2021, ss.28
Introduction
Flap endonuclease 1 (FEN1) involves in DNA replication, long-patch excision repair, and telomere maintenance. FEN1 overexpression has been reported to be associated with the different types of cancers and it might be a predictive biomarker and therapeutic target in some cancers. But still there is no pan-cancer analysis available now.
Method
Through analysis of 33 types of tumors based on the datasets of TCGA and GEO, we conduct the FEN1 gene expression analysis through TIMER2, then based on the CPTAC dataset, we analyzed the total protein expression level of FEN1 between normal tissue and primary tissue of breast cancer, ovarian cancer, colon cancer, clear cell RCC and UCEC. FEN1 genetic alteration evaluated by using cBioPortal web and survival status analyzed with GEPIA2.
Results
Fen1 is highly expressed in most cancers (Fig.1,2). Highly expressed FEN1 was linked to poor prognosis of overall Survival for cancers of LIHC (p=0.007), KICH(p=0.039), ACC(p=0.007), PAAD(p=0.014), MESO(p=0.002), LGG(p=0.019), UVM(p=0.014) and LUAD(p=0.007), while low expression is poor prognosis only in THYM(p=0.04) within the TCGA (Fig.3). The genetic alteration status of FEN1 in different tumor samples of the TCGA cohorts were observed. The highest alteration frequency of FEN1 (> 8%) appeared with primary Cholangiocarcinoma with “CNA amplification” and nearly 5,26% in uterine carcinosarcomas. The “mutation” type was the primary Uterine Corpus Endometrial Carcinomas, which show an alteration frequency of ~3,51% (Fig.4).
Conclusion
It seems FEN1 play a common molecular pathway in the pathogenesis of different tumors. But still remains to be answered. Our pan-cancer study provides a relatively comprehensive understanding of the roles of FEN1 in different tumorigenesis.