Multi-gradient permutation survival analysis identifies mitosis and immune signatures steadily associated with cancer patient prognosis

The inconsistency of the association between genes and cancer prognosis is often attributed to many variables that contribute to patient survival. Whether there exist the <u>G</u>enes St<u>e</u>adily <u>A</u>ssociated with P<u>r</u>ognosis (GEARs) and functions remains largely elusive. Here, we developed a novel method named '<u>M</u>ulti-gradi<u>e</u>nt Per<u>m</u>utati<u>o</u>n Su<u>r</u>vival Anal<u>y</u>sis' (MEMORY) to screen the GEARs by using RNA-seq data from the TCGA database. We employed a network construction approach to identify hub genes from GEARs and utilized them for cancer classification. In the case of lung adenocarcinoma (LUAD), the GEARs were found to be related to mitosis. Our analysis suggested that LUAD cell lines carrying <i>PIK3CA</i> mutations exhibit increased drug resistance. For breast invasive carcinoma (BRCA), the GEARs were related to immunity. Further analysis revealed that <i>CDH1</i> mutation might regulate immune infiltration through the EMT process. Moreover, we explored the prognostic relevance of mitosis and immunity through their respective scores and demonstrated it as valuable biomarkers for predicting patient prognosis. In summary, our study offered significant biological insights into GEARs and highlights their potentials as robust prognostic indicators across diverse cancer types.