Flow cytometry assessment of monocyte subsets alteration in hepatocellular carcinoma post hepatitis C virus infection

Abstract

Hepatocellular carcinoma (HCC) is assumed to be an immunogenic malignancy since 90% of cases develop in environments with ongoing inflammation. Monocyte subsets contribute to tumoral immunity. Most HCC patients are discovered at late stages, which lowers their survival chances. We aimed to determine whether altered frequency of monocyte subsets contribute to post hepatitis C virus infection-liver cirrhosis (HCV-LC) development to HCC. This cross-sectional study enrolled 105 patients classified as post HCV-HCC (n=72) and post HCV-LC (n=33) patients. The monocyte subsets frequency was assessed by flow-cytometry. There was a significant increase in intermediate monocytes and decrease in non-classical monocytes in HCC group when compared to the LC group (P = 0.001 and 0.006, respectively). Intermediate monocyte frequency was positively correlated with cholesterol and triglycerides (r = 0.296, P < 0.002 and r = 0.247, P < 0.011, respectively). The receiver operating characteristic (ROC) curve revealed that intermediate monocytes percentage at a cutoff ≥ 0.625% and non-classical monocytes percentage at a cutoff ≤ 0.61% differentiated between patients with HCV-LC and those with HCV-HCC with a sensitivity of 76.4% and 69.4%, respectively, while both revealed low specificity of 51.5%. According to logistic regression analysis, only the triglyceride level was found to be an independent risk factor for HCC development [OR =1.014 (11.001–1.026), P = 0.031]. Finally, we concluded that post-HCV-HCC is characterized by an upregulation of intermediate monocytes and a downregulation of non-classical monocytes when compared to Post-HCV-LC. Intermediate and non-classical monocytes frequency can aid to screening biomarkers for HCC development. Intermediate monocyte frequency may be linked to hyperlipemia. The level of triglycerides is proposed as an independent risk factor for HCC emergence.

Monocytes Subsets Altered Distribution and Dysregulated Plasma hsa-miR-21-5p and hsa- miR-155-5p in HCV-Linked Liver Cirrhosis Progression to Hepatocellular Carcinoma

“…This would support the potential interest of blood monocytes in monitoring LC development and its progression to HCC. In the same line, our recent research revealed an alteration of intermediate monocytes subset in LC and HCC [34].…”

“…Regarding ROC curve analysis, hsa-miR-21-5p was shown to be superior to hsa-miR-155-5p as a plasma molecular marker for identifying LC cases from healthy cases and combining both hsa-miR-21-5p + hsa-miR-155-5p provided an accepted discriminative sensitivity for HCC cases identi cation from LC [34]. Moreover, logistic regression analysis proved that circulating classical and intermediate monocytes frequencies% and hsa-miR-21-5p were independent predictors of HCC progression from cirrhotic background after adjustment for the confounders (age, BMI, RBS, AFP, and lipids).…”

Monocytes subsets altered distribution and dysregulated plasma hsa-miR-21-5p and hsa-miR-155-5p in HCV-linked liver cirrhosis progression to hepatocellular carcinoma

“…This would support our potential interest in blood monocytes for monitoring LC development and its progression to HCC. In the same line, our recent research revealed an alteration of intermediate monocytes subset in LC and HCC (Ali et al 2022 ).…”

“…Percentage of monocytes subsets was determined from the total monocyte gate, and accordingly, the frequency of the monocytes subsets from the total events acquired was detected. The gating strategy is following the steps of our previous publication Ali et al ( 2022 ). Gating strategy and an example of each patients group are displayed in Fig.…”

miR-183-5p attenuates the effect of sorafenib on human hepatocellular carcinoma via inhibiting SOCS6/JAK2/STAT3 pathway

“…Subsequently, the harvested cells were resuspended in 100 µm annexin V binding buffer (Dojindo, Kumamoto, Japan) supplemented with 1% annexin V-FITC. Flow cytometry analysis was then performed on these cells using BD FACSCanto II (NJ, USA) [31] .…”