The Expression of FLNA and CLU in PBMCs As A Novel Screening Marker for Hepatocellular Carcinoma.

Abstract

Early detection improves survival and increases curative probability in hepatocellular carcinoma (HCC). Peripheral blood mononuclear cells (PBMCs) can provide an inexpensive, less-invasive and highly accurate method. The objective of this study is to find the potential marker for HCC screening, utilizing gene expression of the PBMCs. Data from the NCBI GEO database of gene expression in HCC patients and healthy donor's PBMCs was collected. As a result, GSE 49515 and GSE 58208 were found. Using both, a statistical significance test was conducted in each gene expression of each data set which resulted in 187 genes. We randomized three selected genes (FLNA, CAP1, and CLU) from the significant p-value group (p-values < 0.001). Then, a total of 76 healthy donors and 153 HCC cases were collected. Quantitative RT-PCR (qRT-PCR) was performed in cDNA from all blood samplesFrom the qRT-PCR, The Cycle threshold (Ct) value of FLNA, CLU, CAP1 of HCC group (28.47±4.43, 28.01±3.75, 29.64±3.90) were lower than healthy group (34.23±3.54, 32.90±4.15, 32.18±5.02) (p-values < 0.0001). The accuracy, sensitivity and specificity of these genes as a screening tool were: FLNA (80.8%, 88.0%, 65.8%), CLU (63.4%, 93.3%, 31.3%), CAP1 (67.2%, 83.3%, 39.1%). The tests were performed in two and three gene combinations. Results demonstrated high accuracy of 86.2%, sensitivity of 85% and specificity of 88.4% in the FLNA and CLU combination. We concluded that FLNA and CLU combination have high potential for being HCC novel markers. Combined with current tumor markers, further research of the gene’s expression might help identify more potential markers and improve diagnosis methods.

Identifying Potential New Gene Expression-Based Biomarkers in the Peripheral Blood Mononuclear Cells of Hepatitis B-Related Hepatocellular Carcinoma

“…A recent study reveals that there is a direct relationship between cancer cells and peripheral immune cells [31]. e cytokines should be implicated in the connection between cancer cells and PBMCs [32]. Recent researches indicate that the malignant cells are responsible for the alterations in the secretion of the cytokines from PBMCs and might be associated with cancer progression [33].…”

“…In the present study, after Venn-Diagram analysis, seven representative common genes were identified: TYMP, TYROBP, CD14, TGFBI, LILRA2, GNLY, and GZMB. Recently, several different biomarkers, including CXCR2, CCR2, EP400, SELENBP1, SLC4A1, SLC26A8, HSPA8P4, CALM1, RPL7p24, FLNA, and CLU have been reported to be associated with the progression of HCC [25,27,32]. Nevertheless, no investigation has investigated the expression levels of the seven aforementioned DEGs in PBMC of HBV-HCC patients.…”