Department of Hepatobiliary Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China.
CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences/China National Center for Bioinformation, Beijing, China.
BMC Cancer. 2024 Jun 1;24(1):672. doi: 10.1186/s12885-024-12428-x.
Patients with primary multifocal hepatocellular carcinoma (HCC) have a poor prognosis and often experience a high rate of treatment failure. Multifocal HCC is mainly caused by intrahepatic metastasis (IM), and though portal vein tumor thrombosis (PVTT) is considered a hallmark of IM, the molecular mechanism by which primary HCC cells invade the portal veins remains unclear. Therefore, it is necessary to recognize the early signs of metastasis of HCC to arrange better treatment for patients.
To determine the differential molecular features between primary HCC with and without phenotype of metastasis, we used the CIBERSORTx software to deconvolute cell types from bulk RNA-Seq based on a single-cell transcriptomic dataset. According to the relative abundance of tumorigenic and metastatic hepatoma cells, VEGFA macrophages, effector memory T cells, and natural killer cells, HCC samples were divided into five groups: Pro-T, Mix, Pro-Meta, NKC, and MemT, and the transcriptomic and genomic features of the first three groups were analyzed. We found that the Pro-T group appeared to retain native hepatic metabolic activity, whereas the Pro-Meta group underwent dedifferentiation. Genes highly expressed in the group Pro-Meta often signify a worse outcome.
The HCC cohort can be well-typed and prognosis predicted according to tumor microenvironment components. Primary hepatocellular carcinoma may have obtained corresponding molecular features before metastasis occurred.
患有原发性多灶性肝细胞癌（HCC）的患者预后较差，并且经常经历高治疗失败率。多灶性 HCC 主要由肝内转移（IM）引起，尽管门静脉肿瘤血栓形成（PVTT）被认为是 IM 的标志，但原发性 HCC 细胞侵入门静脉的分子机制尚不清楚。因此，有必要识别 HCC 转移的早期迹象，为患者安排更好的治疗。
为了确定具有和不具有转移表型的原发性 HCC 之间的差异分子特征，我们使用 CIBERSORTx 软件根据单细胞转录组数据集从批量 RNA-Seq 中去卷积细胞类型。根据致瘤性和转移性肝癌细胞、VEGFA 巨噬细胞、效应记忆 T 细胞和自然杀伤细胞的相对丰度，HCC 样本分为 Pro-T、Mix、Pro-Meta、NKC 和 MemT 五组，并分析了前三组的转录组和基因组特征。我们发现 Pro-T 组似乎保留了固有肝代谢活性，而 Pro-Meta 组发生去分化。在 Pro-Meta 组中高表达的基因通常预示着更差的预后。
根据肿瘤微环境成分，可以对 HCC 队列进行良好分型和预后预测。原发性肝细胞癌在转移发生之前可能已经获得了相应的分子特征。
