Spatial Maps of Hepatocellular Carcinoma Transcriptomes Highlight an Unexplored Landscape of Heterogeneity and a Novel Gene Signature for Survival [post]

Nan Zhao, Yanhui Zhang, Runfen Cheng, Danfang Zhang, Fan Li, Yuhong Guo, Zhiqiang Qiu, Xueyi Dong, Xinchao Ban, Baocun Sun, xiulan Zhao
2021 unpublished
Background: Hepatocellular carcinoma (HCC) are often present with satellite nodules, rendering current curative treatments ineffective in many patients. The heterogeneity of HCC is a major challenge in personalized medicine. The emergence of spatial transcriptomics (ST) provides a powerful strategy for delineating the complex molecular landscapes of tumors. Methods: In this study, we investigated tissue-wide gene expression heterogeneity in tumor and adjacent nonneoplastic tissues using ST
more » ... ology. We analyzed the transcriptomes of nearly 10820 tissue regions and identified main gene expression clusters and their specific marker genes (differentially expressed genes, DEGs) in patients. The DEGs were analyzed from two perspectives. First of all, we identified two distinct gene profiles associated with satellite nodules and conducted a more comprehensive analysis for both gene profiles. Their clinical relevance for human HCC was validated with KM Plotter. Secondly, we screened DEGs with TCGA database to divide the HCC cohort into high- and low-risk groups according to Cox analysis. HCC patients from the ICGC cohort were used for validation. Kaplan Meier analysis was used to compare the overall survival (OS) between high- and low-risk groups. Univariate and multivariate Cox analyses were applied to determine the independent predictors for OS. Results: Novel markers for the prediction of satellite nodules and a tumor clusters specific marker genes signature model(6 genes) for HCC prognosis was constructed, respectively. Conclusion: The establishment of marker gene profiles may be an important step towards an unbiased view of HCC and the 6-genes signature can be used for prognostic prediction in HCC. This analysis will help us to clarify one of the possible soucres of HCC heterogeneity, uncover pathogenic mechanisms and novel anti-tumor drug targets.
doi:10.21203/rs.3.rs-812356/v1 fatcat:4lui2litirfojmpqzs5t52tmqu