Advancing precision medicine in colorectal cancer with multi-omics approaches

Colorectal cancer is among the most prevalent and lethal malignancies worldwide, with liver metastases occurring in nearly one-third of patients and accounting for a major share of cancer-related deaths. Traditional research has primarily focused on single genes or pathways, limiting our understanding of the metastatic process and hampering therapeutic progress. The emergence of high-throughput "omics" technologies now allows researchers to probe cancer's complexity at multiple molecular levels. By analyzing DNA, RNA, proteins, metabolites, and microbes, scientists can capture a multidimensional view of tumor evolution and host interaction. Owing to these unresolved clinical challenges, an integrated multi-omics perspective is urgently needed to guide future discoveries in colorectal cancer liver metastasis (CRLM).

The team of Chongqing University Cancer Hospital published a sweeping review (DOI: 10.20892/j.issn.2095-3941.2025.0066) in Cancer Biology & Medicine, synthesizing the latest research on multi-omics in colorectal cancer liver metastasis (CRLM). The article explores how six omics disciplines—genomics, epigenomics, transcriptomics, proteomics, metabolomics, and microbiomics—contribute unique but complementary insights into the mechanisms, diagnosis, treatment, and prognosis of CRLM. This cross-disciplinary overview not only catalogs scientific advances but also advocates for a unified omics approach to tackle one of colorectal cancer (CRC)'s deadliest outcomes.

The review highlights how each omics layer uncovers distinct dimensions of CRLM. Genomic studies reveal key mutations like TP53, KRAS, and SMAD4, and show that metastatic lesions harbor more genetic instability than primary tumors. Epigenomic analyses identify DNA methylation changes and histone modifications—such as hypermethylated TPEF or altered H3K27me3—that could serve as early indicators or drug targets. Transcriptomics brings attention to noncoding RNAs and microRNAs like miR-122, circRNA_0001178, and lncRNA-SNHG15 as potential drivers or markers of metastasis. Proteomic data show structural protein shifts, such as increased ECM proteins and EMT regulators like THBS1, which facilitate invasion. Metabolomic findings reveal how altered pathways, including cholesterol or succinate metabolism, may foster immune exhaustion and resistance. Meanwhile, microbiomics links species like Fusobacterium nucleatum to immunosuppressive microenvironments and therapy response. Crucially, integrated multi-omics studies identify patterns missed by individual layers—for instance, how SMAD4 mutations activate STAT3 signaling to blunt chemotherapy efficacy. Together, these findings present a rich, multidimensional framework for decoding CRLM.

Dissecting cancer through a single lens is no longer enough. By integrating data across the genome, transcriptome, proteome, and beyond, we gain a panoramic view of how colorectal cancer evolves and spreads. This multi-omics synergy opens up new avenues for discovering actionable biomarkers, designing personalized treatments, and ultimately improving survival for patients facing liver metastasis."

Dr. Yan Li, senior author of the review

The implications of this multi-omics paradigm are far-reaching. Clinicians could one day tailor treatment plans using personalized omics profiles, while non-invasive liquid biopsies may track disease progression through cfRNA or methylation markers. Targeting metabolic or microbial factors—like modulating gut microbiota or inhibiting cholesterol-related pathways—could boost immunotherapy outcomes. Although technical and clinical hurdles remain, the review strongly advocates for integrating omics in both research and practice. As these methods mature, they promise to reshape how colorectal liver metastasis is detected, treated, and prevented—moving precision medicine from concept to clinic.