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Proteome expression profile for red blood cells enables early diagnostics for hepatocellular carcinoma

ABSTRACT: Early diagnosis of hepatocellular carcinoma (HCC) has not been clinically resolved, which has been causing more death in patients with HCC. HCC is a systemic disease related to disorders of blood homeostasis, and the association of red blood cells (RBCs) and HCC tumorigenesis has been still elusive. We performed data independent acquisition (DIA) proteomic analyses with 72 clinical RBCs samples including HCC (n = 30), liver cirrhosis (LC, n = 17) and healthy controls (n = 25), and characterized the clinical relevanve of RBCs and tumorigenesis in HCC. We observed that RBCs dynamically changes during the tumorigenesis of HCC, and LC is a developmental stage closely approaching HCC based on the protein expresson profiles in RBCs. The expression of hemoglobin (HbA, HbF) in peripheral blood dynamically changes during the whole process of HCC tumorigenesis, suggesting immature erythroid cells exist in peripheral blood of HCC patients and erythropoiesis in the patients begins to be influenced with the occurance of LC. We also identified the disturbed autophagy pathway in RBCs with the onset of LC and maintained during the tumorigenesis of HCC. Oxytocin pathway and GnRH pathway are disturbed and first identified during the development of LC into HCC. SMIM1, ANXA7, HBA1 and HBE1 that are significantly altered during tumorigenesis were verified with parallel reaction monitoring (PRM) technology as promising biomarkers for HCC early diagnosis. This study could facilitate the understanding of the tumorigenesis of HCC from a different view and early diagnosis for HCC.

ORGANISM(S): Homo Sapiens

SUBMITTER: Zhaojun Zhang

PROVIDER: PXD035464 | iProX | Thu Jul 21 00:00:00 BST 2022

REPOSITORIES: iProX

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Project description:In cancer management, early and accurate diagnosis of hepatocellular carcinoma (HCC) is important for enhancing survival rate of patients. Currently, serum alpha-fetoprotein (AFP) is the only one biomarker for detection of HCC. However, serum AFP is not satisfactory for diagnosis of HCC due to its low accuracy (about 60-70%). In this study, we collected 109 serum samples (discovery set) from healthy control (HC) and patients with chronic hepatitis B (CHB), liver cirrhosis (LC) and HCC, and analyzed them with custom lncRNA microarray. Profiling analysis shows 181 differentially expressed lncRNAs between HCs and patients with CHB, LC and HCC. Then a 48-lncRNA diagnostic signature was identified with 100% predictive accuracy for all subjects in the discovery set. This diagnostic signature was verified with a cross-validation analysis in the discovery set. To further corroborate the signature, we gathered another 66 serum samples (validation set) and also analyzed them with microarray. The result indicates that the same signature has similar diagnostic accuracy for HC (100%), CHB (73%), LC (88%) and HCC (95%), implying a reproducible diagnostic biomarker for HCC. Receiver operating characteristic (ROC) analysis exhibits that this signature has significantly higher diagnostic accuracy for HCC and non-cancerous subjects (area under curve [AUC]: 0.994) than AFP (AUC: 0.773) in the discovery set and this was also verified in the validation set (0.964 vs 0.792). More importantly, the signature detected small HCC (<3cm) with 100% (13/13) accuracy while AFP with only 61.5% (8/13). Altogether, this study demonstrates that the serum 48-lncRNA signature is not only a powerful and sensitive biomarker for diagnosis of HCC but also a potential biomarker for LC. ***************************************************************** Submitter declares these data are subject to patent number ZL 2016 1 0397094. *****************************************************************

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Proteome expression profile for red blood cells enables early diagnostics for hepatocellular carcinoma

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