Раковая наука и терапия

Tumor-Induced GIMAP8 Expression in Peripheral Blood Mononuclear Cells as a Novel Marker for Epithelial Ovarian Cancer Detection

Abstract

Natthamon Sonthi, Chatchawit Aporntewan, Shina Oranratanaphan, Tarinee Manchana, Natacha Phoolcharoen, Nakarin Kitkumthorn and Apiwat Mutirangura

Cancer cells change the properties of surrounding cells via secretion signaling. The effects of tumor communication were found to cause molecular alterations in peripheral blood mononuclear cells (PBMCs). These alterations could be applied in a blood-based test for cancer detection, especially with epithelial ovarian cancer (EOC). This cancer has less effective screening tools and nonspecific symptoms leading to high mortality rates in patients. Therefore, a novel biomarker for screening is required. A simulated model of cancer cell signaling was performed by the co-culture of normal PBMCs with ovarian cancer cell lines. Transcriptome analysis was then performed using RNA sequencing (RNA-seq). In addition, we retrieved expression microarray (GSE31682) data from GenBank and combined this expression data with the two groups of RNA-seq data using Connection Upand Down-Regulation Expression Analysis of Microarrays extension (CU-DREAMX). The most upregulated gene, GTPase IMAP family member eight (GIMAP8), was selected for validation by quantitative reverse transcription polymerase chain reaction in PBMCs from 16 ovarian cancer patients compared with 15 healthy controls. The GIMAP8 expression was significantly increased in ovarian cancer patients (p-value < 0.0001). Interestingly, there was high expression in all three cases of clear cell and four cases of serous adenocarcinoma. We determined that PBMCs changed their gene expression as a result of ovarian cancer cell signaling. Furthermore, the expression level changes in GIMAP8 could be applied for cancer screening, diagnosis, and treatment monitoring purposes.