Cancer Stem Cells and Cell Cycle Genes as Independent Predictors of Relapse in Non-small Cell Lung Cancer: Secondary Analysis of a Prospective Study

Purpose Cancer stem cells (CSCs) are described as resistant to chemotherapy and radiotherapy. It has been shown that CSCs influence disease-free survival in patients undergoing surgery for lung cancer (NCT04634630). We recently described an overexpression of CSCs recurrence-related genes (RG) in lung cancer. This study aims to investigate CSC frequency and RG expression as predictors of disease-free survival in lung cancer. Experimental Design This secondary analysis of a prospective cohort study involved 22 surgical tumor specimens from 22 patients harboring early (I-II) and locally advanced (IIIA) stages ACL and SCCL. Cell population frequency analysis of ALDH(high) (CSCs) and ALDH(low) (cancer cells) was performed on each tumor specimen. In addition, RG expression was assessed for 31 target genes separately in ALDH(high) and ALDH(low) populations. CSCs frequency and RG expression were assessed as predictors of disease-free survival by Cox analysis. Results CSCs frequency and RG expression were independent predictors of disease-free survival. CSC frequency was not related to disease-free survival in early-stage patients (HR = 0.84, 95%CI = 0.53-1.33, P = .454), whereas it was a risk factor for locally advanced-stage patients (HR = 1.22, 95%CI = 1.09-1.35, P = .000). RG expression-if measured in CSCs-was related to a higher risk of recurrence (HR = 1.19, 95%CI = 1.03-1.39, P = .021). The effect of RG expression measured in cancer cells on disease-free survival was lower and was not statistically significant (HR = 1.12, 95%CI = 0.94-1.33, P = .196). Conclusions CSCs frequency and RG expression are independent predictors of relapse in lung cancer. Considering these results, CSCs and RG may be considered for both target therapy and prognosis.

Automated summary

This study found that the frequency of cancer stem cells (CSCs) and the expression of recurrence-related genes (RG) are independent predictors of disease-free survival in lung cancer. The frequency of CSCs is not related to disease-free survival in early-stage patients, but is a risk factor for locally advanced-stage patients. Moreover, measuring the expression of RG in CSCs is associated with a higher risk of recurrence. These findings suggest that CSCs and RG may have implications for targeted therapy and prognosis in lung cancer.