CELLS CYCLE GENES IN CANCER STEM CELLS MOSTLY ASSOCIATED TO RECURRENCE IN NON-SMALL CELL LUNG CANCER (NSCLC).

Cancer stem cells (CSCs) are described as resistant to chemotherapy and radiotherapy. We have previously shown that CSCs influence disease-free survival in patients undergoing surgery for lung cancer (<ext-link>NCT04634630</ext-link>). Moreover, we recently described an association between the combined expression of recurrence-related cell cycle genes (RG) in lung CSCs. Among a previously analyzed pool of RGs, we aim to show the single genes more associated with the risk of recurrence in lung cancer. This is secondary analysis of a prospective cohort study involving 22 surgical tumor specimens from 22 patients harboring early (I-II) and locally advanced (IIIA) stages of ACL and SCCL. RGs population frequency analysis in ALDHhigh (CSCs) was performed on each tumor specimen. Among the pool of previously analyzed 31 RGs, we described those single genes most associated to the risk of recurrence in lung cancer. Results were reported as the hazard ratio (HR) related to a 1-unit decrease in RGs’ cycle thresholds, based on robust Cox analysis. Statistical significance was set at p < 0.05. RGs associated with the highest risk of recurrence were FOXM1 (HR = 1,462; p= 0.028), PRC1 (HR = 1,344 ; p = 0,050), CENPF (HR = 1,337 ; p = 0,017), and KIF20A (HR = 1,228 ; p = 0,009). Other genes such as CDCA8, RRM2, CDKN3, PLK1, and CENPM showed a high HR, although no statistically significant association has been observed. Our study is the first attempt showing the most recurrence-related risk genes in lung CSCs. This would be of crucial importance to set further studies investigating the roles of these genes and their molecular pathways into lung cancer risk, as well as cancer progression and metastasis.