{"title":"A sub-cluster of cancer cells indicates poor prognosis in advanced hepatocellular carcinoma.","authors":"Hai-Feng Zhou, Wei Yang, Fei-Da Wu, Di Zhu, Yu-Guan Xie, Bi-Fei Wu, Zhi-Hui Hong, Hai-Bin Shi, Sheng Liu, Wei-Zhong Zhou","doi":"10.21037/cco-24-58","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>For patients with advanced hepatocellular carcinoma (HCC), it is emergent to focus on elucidating different classifications of intratumoral heterogeneity and understanding the mechanisms of treatment resistance to improve prognosis. This study aims to classify the sub-clusters of cancer cells in patients diagnosed with advanced HCC, and identify the genes, pathways and microenvironment associated with prognosis.</p><p><strong>Methods: </strong>Single-cell transcriptomic profiling were conducted on advanced HCC samples. Bulk RNA-seq transcriptome data were obtained from The Cancer Genome Atlas (TCGA) database. Prognosis analysis was performed for survival stratification within the identified sub-clusters. Enriched genes and pathways were determined, and the association and underlying mechanism of the identified sub-cluster of cancer cells were elucidate with other cellular components within advanced HCC tumor tissue.</p><p><strong>Results: </strong>A total of 26,800 cells were obtained from two patients with advanced HCC. Seven sub-clusters were identified, and only the CancerCell 6 cluster were exhibited significant disparities in both overall survival (OS) and progression-free survival (PFS) rates according to the 370 HCC patients from the TCGA database. The CancerCell 6 cluster was associated with adenosine triphosphate (ATP)-related pathways and the high expression of pyruvate kinase M (PKM). It also demonstrated a strong interaction ability with mononuclear phagocytes (MPs). The MPs_MMP9 cluster showed strong interactions between the CancerCell 6 cluster and related signaling pathways of EDN and NOTCH, indicating a tendency toward M2 polarization.</p><p><strong>Conclusions: </strong>This study identified the CancerCell 6 cluster associated with a poor prognosis and characterized by ATP-related metabolism. This cluster demonstrated interactions with MPs inclined to M2 polarization.</p>","PeriodicalId":9945,"journal":{"name":"Chinese clinical oncology","volume":"14 1","pages":"1"},"PeriodicalIF":2.1000,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Chinese clinical oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21037/cco-24-58","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: For patients with advanced hepatocellular carcinoma (HCC), it is emergent to focus on elucidating different classifications of intratumoral heterogeneity and understanding the mechanisms of treatment resistance to improve prognosis. This study aims to classify the sub-clusters of cancer cells in patients diagnosed with advanced HCC, and identify the genes, pathways and microenvironment associated with prognosis.
Methods: Single-cell transcriptomic profiling were conducted on advanced HCC samples. Bulk RNA-seq transcriptome data were obtained from The Cancer Genome Atlas (TCGA) database. Prognosis analysis was performed for survival stratification within the identified sub-clusters. Enriched genes and pathways were determined, and the association and underlying mechanism of the identified sub-cluster of cancer cells were elucidate with other cellular components within advanced HCC tumor tissue.
Results: A total of 26,800 cells were obtained from two patients with advanced HCC. Seven sub-clusters were identified, and only the CancerCell 6 cluster were exhibited significant disparities in both overall survival (OS) and progression-free survival (PFS) rates according to the 370 HCC patients from the TCGA database. The CancerCell 6 cluster was associated with adenosine triphosphate (ATP)-related pathways and the high expression of pyruvate kinase M (PKM). It also demonstrated a strong interaction ability with mononuclear phagocytes (MPs). The MPs_MMP9 cluster showed strong interactions between the CancerCell 6 cluster and related signaling pathways of EDN and NOTCH, indicating a tendency toward M2 polarization.
Conclusions: This study identified the CancerCell 6 cluster associated with a poor prognosis and characterized by ATP-related metabolism. This cluster demonstrated interactions with MPs inclined to M2 polarization.
期刊介绍：
The Chinese Clinical Oncology (Print ISSN 2304-3865; Online ISSN 2304-3873; Chin Clin Oncol; CCO) publishes articles that describe new findings in the field of oncology, and provides current and practical information on diagnosis, prevention and clinical investigations of cancer. Specific areas of interest include, but are not limited to: multimodality therapy, biomarkers, imaging, tumor biology, pathology, chemoprevention, and technical advances related to cancer. The aim of the Journal is to provide a forum for the dissemination of original research articles as well as review articles in all areas related to cancer. It is an international, peer-reviewed journal with a focus on cutting-edge findings in this rapidly changing field. To that end, Chin Clin Oncol is dedicated to translating the latest research developments into best multimodality practice. The journal features a distinguished editorial board, which brings together a team of highly experienced specialists in cancer treatment and research. The diverse experience of the board members allows our editorial panel to lend their expertise to a broad spectrum of cancer subjects.
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