Elevated soluble TNFα levels and upregulated TNFα mRNA expression in purified peripheral blood monocyte subsets associated with high-grade hepatocellular carcinoma

Martín-Sierra, Carmen; Martins, Ricardo; Coucelo, Margarida; Abrantes, Ana Margarida; Oliveira, Rui Caetano; Tralhão, José Guilherme; Botelho, Maria Filomena; Furtado, Emanuel; Domingues, M. Rosário M.; Paiva, Artur; Laranjeira, Pires

doi:10.1186/s12950-020-00243-7

Cited by 7 publications

(4 citation statements)

References 36 publications

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“…Therefore, monocytes may present one important component, via atherosclerosis development, during the liver fibrotic stage preceding or early during LC. According to Martín-Sierra et al ( 2020 ), intermediate-monocyte subsets through their pro-inflammatory role are related to HCC tumorigenicity in CHCV G4 Egyptian patients. Since hsa-miR-21-5p over-expression, in the disease groups, was positively correlated with intermediate monocytes percentage, therefore, we can hypothesize that up-regulated hsa-miR-21-5p may be involved in monocytes differentiation (Cekaite et al 2010 ).…”

Section: Discussionmentioning

confidence: 99%

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

Hammad,

Eldosoky,

Elmadbouly

et al. 2023

J Cancer Res Clin Oncol

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Purpose The authors aim to investigate the altered monocytes subsets distribution in liver cirrhosis (LC) and subsequent hepatocellular carcinoma (HCC) in association with the expression level of plasma Homo sapiens (has)-miR-21-5p and hsa-miR-155-5p. A step toward non-protein coding (nc) RNA precision medicine based on the immune perturbation manifested as altered monocytes distribution, on top of LC and HCC. Methods Seventy-nine patients diagnosed with chronic hepatitis C virus (CHCV) infection with LC were enrolled in the current study. Patients were sub-classified into LC group without HCC (n = 40), LC with HCC (n = 39), and 15 apparently healthy controls. Monocyte subsets frequencies were assessed by flow cytometry. Real-time quantitative PCR was used to measure plasma hsa-miR-21-5p and hsa-miR-155-5p expression. Results Hsa-miR-21-5p correlated with intermediate monocytes (r = 0.30, p = 0.007), while hsa-miR-155-5p negatively correlated with non-classical monocytes (r = − 0.316, p = 0.005). ROC curve analysis revealed that combining intermediate monocytes frequency and hsa-miR-21 yielded sensitivity = 79.5%, specificity = 75%, and AUC = 0.84. In comparison, AFP yielded a lower sensitivity = 69% and 100% specificity with AUC = 0.85. Logistic regression analysis proved that up-regulation of intermediate monocytes frequency and hsa-miR-21-5p were independent risk factors for LC progression to HCC, after adjustment for co-founders. Conclusion Monocyte subsets differentiation in HCC was linked to hsa-miR-21-5p and hsa-miR-155-5p. Combined up-regulation of intermediate monocytes frequency and hsa-miR-21-5p expression could be considered a sensitive indicator of LC progression to HCC. Circulating intermediate monocytes and hsa-miR-21-5p were independent risk factors for HCC evolution, clinically and in silico proved. Graphical abstract

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Section: Discussionmentioning

confidence: 99%

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

Hammad,

Eldosoky,

Elmadbouly

et al. 2023

J Cancer Res Clin Oncol

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“…This change seems cancer-type-dependent as the level of intermediate monocytes is significantly lower in squamous cell carcinoma of the head and neck (SCCHN) than that in healthy donors [ 7 ]. Similarly, a significant expansion of non-classical monocytes is observed in endometrial and breast cancer patients when compared with healthy controls [ 8 ], while a marked decrease in monocytes was detected in both cholangiocarcinoma (CCA) and hepatocellular carcinoma (HCC) patients before and after surgical procedures [ 9 ].…”

Section: The Global Effects Of Tme On Monocytesmentioning

confidence: 99%

Monocytes in Tumorigenesis and Tumor Immunotherapy

Chen

Xia

et al. 2023

Cells

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Monocytes are highly plastic innate immune cells that display significant heterogeneity during homeostasis, inflammation, and tumorigenesis. Tumor-induced systemic and local microenvironmental changes influence the phenotype, differentiation, and distribution of monocytes. Meanwhile, monocytes and their related cell subsets perform an important regulatory role in the development of many cancers by affecting tumor growth or metastasis. Thanks to recent advances in single-cell technologies, the nature of monocyte heterogeneity and subset-specific functions have become increasingly clear, making it possible to systematically analyze subset-specific roles of monocytes in tumorigenesis. In this review, we discuss recent discoveries related to monocytes and tumorigenesis, and new strategies for tumor biomarker identification and anti-tumor immunotherapy.

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“…2 Therefore, immunotherapeutic techniques would be the most appropriate therapeutic options to use in these sorts of carcinomas. 5 As innate immune cells, monocytes phagocytose microbes and produce oxygen reactive species. They also play a role in cellular processes such as tissue repair and regeneration during heart diseases.…”

Section: Introductionmentioning

confidence: 99%

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

Ali

Hammad

Kotb

et al. 2022

EJI

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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.

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Elevated soluble TNFα levels and upregulated TNFα mRNA expression in purified peripheral blood monocyte subsets associated with high-grade hepatocellular carcinoma

Cited by 7 publications

References 36 publications

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

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

Monocytes in Tumorigenesis and Tumor Immunotherapy

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

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