The new nomenclature for LUAD molecular subtype is a key step in lung cancer diagnosis and treatment. The molecular classification is characterized by specific genetic alterations, including histopathological, anatomic, and mutational categorizations. Analysis of the TCGA transcriptional profiling data has provided 3 molecular subtypes of LUAD. (1) The PI subtype was characterized by the Solid architecture with enrichment for NF1 and TP53 in addition to p16 methylation. (2) The PP subtype was enriched for mutations and CNAs in KRAS and STK11, along with variable histology. (3) The TRU subtype harbored mutations or CNAs in EGFR and kinase fusions. Among the three molecular subtypes, TRU has the most favorable prognosis. The TRU subtype presents more commonly in women who never smoked, characterized by Acinar, Papillary, or Lepidic histomorphology. In this work, the gene expression level of ZDHHC5 is highest in PI, relatively low in TRU, and lowest in PP (Supplementary Figure 1B). Although the result is not statistically significant, we still attribute it to the cancer-promoting effect of ZDHHC5, considering the small sample size.
