Platelets’ RNA as biomarker trove for differentiation of early-stage hepatocellular carcinoma from underlying cirrhotic nodules

Abstract

Background & aims Among the multiplicity of factors involved in rising incidence of hepatocellular carcinoma (HCC)-the second deadliest cancer, late diagnosis of early-stage HCC nodules originating from late-stage cirrhotic nodules is the most crucial. In recent years, Tumor-educated platelets (TEPs) have emerged as a strong multimodal tool to be used in liquid-biopsy of cancers because of changes in their mRNA content. This study assessed the reliability of selected mRNA repertoire of platelets as biomarkers to differentiate early HCC from late-stage cirrhotic nodules. Methods Quantitative real time PCR (qRT-PCR) was used to evaluate expression levels of selected platelets-specific mRNA between HCC patients compared to cirrhosis patients. ROC curve analysis assessed the sensitivity and specificity of the biomarkers. Results RhoA, CTNNB1 and SPINK1 showed a significant 3.3-, 3.2- and 3.18-folds upregulation, respectively, in HCC patients compared to cirrhosis patients while IFITM3 and SERPIND1 presented a 2.24-fold change. Strikingly, CD41+ platelets also demonstrated a marked difference of expression in HCC and cirrhosis groups. Conclusions Our study reports liquid biopsy-based platelets mRNA signature for early diagnosis of HCC from underlying cirrhotic nodules. Moreover, differential expression of CD41+ platelets in two groups provides new insights into a probable link between CD41 expression on platelets with the progression of cirrhosis to HCC.

Clinical Application of Different Liquid Biopsy Components in Hepatocellular Carcinoma

“…Likewise, mRNAs such as CTNNB1, Rho A, SPINK1, IFITM3, and SERPIND1 contained in TEPs could permit earlier diagnosis of HCC from cirrhotic nodules. This result was evidenced in a 50-person cohort comprised of healthy subjects, patients with HCC, and cirrhosis [217]. By the bioinformatic analysis of platelet miRNAs, 250 miRNAs with differential expression were identified in blood samples from HCC patients and controls.…”

Prediction of Potential Biomarkers in Early-Stage Nasopharyngeal Carcinoma Based on Platelet RNA Sequencing

“…In recent years, TEP RNA has become a research hotspot as a biomarker in tumour detection. It has been reported that platelet RNA can be used as a biomarker to distinguish early liver cancer from nodules of cirrhosis [21]. Sidra Asghar et al found that AKT expression in platelets of early HCC was reduced by 0.6 times and PI3K expression was reduced by 0.65, indicating a potential as diagnostic markers for early HCC [22].…”

Prospects of liquid biopsy in the prognosis and clinical management of gastrointestinal cancers

“…Across cancer types, studies stated the valuable role of TEPs in carrying tumor mutational signatures as RNA profiles and indicated their potential role fit to be used for pan-cancer diagnostic utilities ( Best et al, 2015 ). Many studies in the scientific domain report mRNA profile changes in TEPs in various cancer types, such as non-small cell lung cancer (NSCLC) ( Luo L. et al, 2018 ; Xue et al, 2018 ; Dong et al, 2021 ), breast cancer ( Mendoza-Almanza et al, 2020 ), liver cancer ( Best and Wurdinger, 2020 ; Waqar et al, 2021 ), and glioma ( Campanella et al, 2020 ). Some studies have also investigated and found the role of medium-sized extracellular vesicles (EVs) (mEVs) exuviated by platelets activated by thrombins to carry prognostic clues ( Contursi et al, 2023 ).…”