Our data also have clinical implications, as germline polymorphisms and tumor gene expression levels of ZNRF3/RNF43 and RSPO may be related to tumor response to anti-EGFR monoclonal antibody cetuximab-based treatment in CRC patients (Battaglin et al. 2020; Elez et al. 2022), providing insights into understanding the interplay between RSPO-ZNRF3/RNF43 and EGFR protein levels and anti-EGFR activity in CRC treatment. Here, ZNRF3 is linked to neoplasm.