The TME is highly heterogeneous, and some studies have deciphered the molecular subtypes of ESCC based on the somatic mutation profile and copy number variation on the genome.44,45 Wang et al. identified three ESCC molecular subtypes with different prognosis, characterized by glycogen metabolism downregulation, Wnt signaling pathway activation, and immunosuppression.15 For Wnt signaling pathway activation,however, it was activated by FadA of Fn in colorectal cancer.46These findings suggest that microbes may be associated with the formation of specific cell clusters within the TME. The gene discussed is FN1; the disease is colorectal cancer.