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Researchers Find Genetic, Cellular Features of Early-Onset Colorectal Cancer in Chinese Patients

NEW YORK – In a new multiomics study, researchers in China have unraveled the genetic and molecular signatures of early-onset colorectal cancer (EOCRC) in Chinese patients and determined how these features differ from late-onset colorectal cancer (LOCRC).

EOCRC tends to be diagnosed at a more advanced stage compared to LOCRC. "The increasing rate of patients with early-onset colorectal cancer, who are diagnosed before 50 years of age, is of great concern, especially in China," the authors noted. Previous multiomics studies in colorectal cancers have mainly focused on European populations, they added.

For this study, published in Cell Reports Medicine on Wednesday, researchers profiled the genomes, epigenomes, transcriptomes, and proteomes of tumors of 79 patients with colorectal cancers — 30 patients with EOCRC and 49 with LOCRC — from the Nanjing Colorectal Cancer cohort.

They additionally got data for 126 EOCRC patients from the International Cancer Genome Consortium Chinese cohort and The Cancer Genome Atlas European cohort.

While whole-genome and exome sequencing studies of the Nanjing cohort revealed 11 mutated genes, some of these were different from what was previously seen in European cohorts. For instance, Nanjing cohort tumors showed significantly lower mutation frequencies of APC and FBXW7 than those from the TCGA European cohort.

"These results were consistent with a previous ancestry comparison between Asian and European subjects," authors noted.

Researchers also found EOCRC tumors had higher tumor mutation burden (TMB) compared to LOCRC tumors — an important independent genomic biomarker indicating the likelihood of a response to immunotherapy.

Meanwhile, transcriptomic profiling showed that EOCRC had higher immune infiltration. Next, using transcriptomic profiling, the researchers classified the tumors into different subtypes and found that EORC samples had a high proportion of "hot tumors," which are known to respond well to immunotherapy. "These new findings on the differences between EOCRC and LOCRC would provide valuable insight into development of precision therapies," said the authors.

Another important finding from this study was that higher levels of LMTK3 gene mutations were observed in EORC tumor samples from China compared to those in European populations. Researchers noted LMTK3 as an important modulator, biomarker, and therapeutic target for precision oncology in EORC.

Highlighting the limitations, the authors wrote that that some of the "insignificant" findings about molecular alterations could be because of limited samples used for this study. They also didn't look at posttranslational modifications or perform trans-omics-based subtype analysis.

"These limitations restrict the synergy of multiomics analysis to provide a unified view of the molecular heterogeneity of EOCRC," authors said.