AUTHOR=Turyova Eva , Mikolajcik Peter , Grendar Marian , Kudelova Eva , Holubekova Veronika , Kalman Michal , Marcinek Juraj , Hrnciar Matej , Kovac Michal , Miklusica Juraj , Laca Ludovit , Lasabova Zora 

TITLE=Expression of OCT4 isoforms is reduced in primary colorectal cancer

JOURNAL=Frontiers in Oncology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1166835

DOI=10.3389/fonc.2023.1166835

ISSN=2234-943X

ABSTRACT=<sec><title>Introduction</title><p>Colorectal cancer (CRC) is one of the most common types of cancer worldwide. The carcinogenesis of CRC is indeed complex, and there are many different mechanisms and pathways that contribute to the development of malignancy and the progression from primary to metastatic tumors. The OCT4A, encoded by the <italic>POU5F1</italic> gene, is a transcription factor responsible for the phenotype of stem cells, maintaining pluripotency and regulation of differentiation. The <italic>POU5F1</italic> gene is made up of five exons that can create numerous isoforms through alternative promoter or alternative splicing. In addition to <italic>OCT4A</italic>, other isoforms called <italic>OCT4B</italic> are also translated into protein; however, their role in cells has been unclear. The aim of our work was to investigate the expression patterns of <italic>OCT4</italic> isoforms in primary and metastatic CRC, providing us with useful information about their role in the development and progression of CRC.</p></sec><sec><title>Methods</title><p>Surgical specimens from a total of 78 patients were collected and isolated from primary tumors (<italic>n</italic> = 47) and metastases (<italic>n</italic> = 31). The relative gene expression of <italic>OCT4</italic> isoforms was investigated using the RT-qPCR method together with the TaqMan probes for particular <italic>OCT4</italic> isoforms.</p></sec><sec><title>Results</title><p>Our results suggest significantly downregulated expression of the <italic>OCT4A</italic> and <italic>OCT4Bs</italic> isoforms in both primary (<italic>p</italic> = 0.0002 and <italic>p</italic> &lt; 0.0001, respectively) and metastatic tumors (<italic>p</italic> = 0.0006 and <italic>p</italic> = 0.00051, respectively) when compared with the control samples. We also observed a correlation between reduced expression of all <italic>OCT4</italic> isoforms and both primary and left-sided tumors (<italic>p</italic> = 0.001 and <italic>p</italic> = 0.030, respectively). On the other hand, the expression of all <italic>OCT4</italic> isoforms was significantly upregulated in metastases compared with primary tumors (<italic>p</italic> &lt; 0.0001).</p></sec><sec><title>Discussion</title><p>Unlike previous reports, we found out that the expression of <italic>OCT4A</italic>, <italic>OCT4Bs</italic>, and all <italic>OCT4</italic> isoforms was significantly reduced in primary tumors and metastases compared with control samples. On the other hand, we supposed that the expression rate of all <italic>OCT4</italic> isoforms may be related to the cancer type and side, as well as to liver metastases. However, further studies are required to investigate the detailed expression patterns and significance of individual <italic>OCT4</italic> isoforms in carcinogenesis.</p></sec>