The comparative integrated multi-omics analysis identifies CA2 as a novel target for chordoma Running title: The integrated multi-omics analysis in chordoma

The first comparative integrated multi-omics analysis of gene expression, open chromatin region and chromatin spatial organization was generated between chordoma and notochord-derived nucleus pulposus cells with the largest sample validation. The differentially hierarchical structures along with the findings in imageological examination and clinical information from external databases indicated the crucial roles of bone microenvironment in the tumorigenesis of chordoma. Besides, based on clinical samples validation and functional experiments, a novel therapeutic target (CA2) was identified for chordoma. Our findings also suggest Dorzolamide HCl as a promising drug for chordoma treatment.