The Blood Transfusion Department, First Medical Center of Chinese PLA General Hospital, Beijing, China.
State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, China.
PLoS One. 2022 Nov 8;17(11):e0276904. doi: 10.1371/journal.pone.0276904. eCollection 2022.
The early diagnosis of hepatocellular carcinoma (HCC) has not been clinically elucidated, leading to an increased mortality rate in patients with HCC. HCC is a systemic disease related to disorders of blood homeostasis, and the association between red blood cells (RBCs) and HCC tumorigenesis remains elusive. We performed data-independent acquisition proteomic analyses of 72 clinical RBC samples, including HCC (n = 30), liver cirrhosis (LC, n = 17), and healthy controls (n = 25), and characterized the clinical relevance of RBCs and tumorigenesis in HCC. We observed dynamic changes in RBCs during HCC tumorigenesis, and our findings indicate that, based on the protein expression profiles of RBCs, LC is a developmental stage closely approaching HCC. The expression of hemoglobin (HbA and HbF) in peripheral blood dynamically changed during HCC tumorigenesis, suggesting that immature erythroid cells exist in peripheral blood of HCC patients and that erythropoiesis is influenced by the onset of LC. We also identified the disrupted autophagy pathway in RBCs at the onset of LC, which persisted during HCC tumorigenesis. The oxytocin and GnRH pathways were disrupted and first identified during the development of LC into HCC. Significantly differentially expressed SMIM1, ANXA7, HBA1, and HBE1 during tumorigenesis were verified as promising biomarkers for the early diagnosis of HCC using parallel reaction monitoring technology. This study may enhance the understanding of HCC tumorigenesis from a different point of view and aid the early diagnosis of HCC.
肝细胞癌 (HCC) 的早期诊断尚未在临床上得到阐明，导致 HCC 患者的死亡率增加。HCC 是一种与血液内稳态紊乱相关的全身性疾病，红细胞 (RBC) 与 HCC 肿瘤发生之间的关联仍不清楚。我们对 72 例临床 RBC 样本进行了非依赖性数据获取蛋白质组学分析，包括 HCC（n=30）、肝硬化（LC，n=17）和健康对照（n=25），并对 RBC 的临床相关性和 HCC 肿瘤发生进行了特征描述。我们观察到 RBC 在 HCC 肿瘤发生过程中的动态变化，我们的研究结果表明，根据 RBC 的蛋白质表达谱，LC 是一个接近 HCC 的发育阶段。血红蛋白 (HbA 和 HbF) 在 HCC 肿瘤发生过程中在外周血中的表达动态变化，表明 HCC 患者外周血中存在未成熟的红细胞，并且红细胞生成受到 LC 发病的影响。我们还在 LC 发生时鉴定了 RBC 中破坏的自噬途径，该途径在 HCC 肿瘤发生过程中持续存在。在 LC 发展为 HCC 的过程中，催产素和 GnRH 途径被破坏并首次被发现。使用平行反应监测技术验证了在肿瘤发生过程中差异表达的 SMIM1、ANXA7、HBA1 和 HBE1 作为 HCC 早期诊断的有前途的生物标志物。这项研究可能从不同的角度增强对 HCC 肿瘤发生的理解，并有助于 HCC 的早期诊断。
