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Observational Study
. 2022 Mar 31;11(3):239-247.
doi: 10.1093/stcltm/szab029.

The Influence of Cancer Stem Cells on the Risk of Relapse in Adenocarcinoma and Squamous Cell Carcinoma of the Lung: A Prospective Cohort Study

Valentina Masciale  1   2 , Federico Banchelli  3 , Giulia Grisendi  2 , Roberto D'Amico  3 , Antonino Maiorana  4 , Alessandro Stefani  1 , Uliano Morandi  1 , Franco Stella  5 , Massimo Dominici  2 , Beatrice Aramini  1   5
Affiliations
Observational Study

The Influence of Cancer Stem Cells on the Risk of Relapse in Adenocarcinoma and Squamous Cell Carcinoma of the Lung: A Prospective Cohort Study

Valentina Masciale et al. Stem Cells Transl Med. .

Abstract

Purpose: Lung cancer relapse may be associated with the presence of a small population of cancer stem cells (CSCs) with unlimited proliferative potential. Our study assessed the relationship between CSCs and the relapse rate in patients harboring adenocarcinoma (ADL) and squamous cell carcinoma of the lung (SCCL).

Experimental design: This is an observational prospective cohort study (NCT04634630) assessing the influence of CSC frequency on relapse rate after major lung resection in 35 patients harboring early (I-II) (n = 21) and locally advanced (IIIA) (n = 14) ADL and SCCL. There was a 2-year enrollment period followed by a 1-year follow-up period. Surgical tumor specimens were processed, and CSCs were quantified by cytofluorimetric analysis.

Results: Cancer stem cells were expressed in all patients with a median of 3.1% of the primary cell culture. Primary analysis showed no influence of CSC frequency on the risk of relapse (hazard ratio [HR] = 1.05, 95% confidence interval [CI] = 0.85-1.30). At secondary analysis, patients with locally advanced disease with higher CSC frequency had an increased risk of relapse (HR = 1.26, 95% CI = 1.14-1.39), whereas this was not observed in early-stage patients (HR = 0.90, 95% CI = 0.65-1.25).

Conclusion: No association was found between CSC and relapse rates after major lung resection in patients harboring ACL and SCCL. However, in locally advanced-stage patients, a positive correlation was observed between CSC frequency and risk of relapse. These results indicate a need for further molecular investigations into the prognostic role of CSCs at different lung cancer stages.

Clinical trial registration: NCT04634630.

Keywords: cancer stem cells; early stages; locally advanced stage; non–small cell lung cancer; relapse.

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Figures

Graphical Abstract
Graphical Abstract
Figure 1.
Figure 1.
Flow chart of study enrolment.
Figure 2.
Figure 2.
Lung tumorspheres. In vitro at 7 days of culture representative of the formation of lung tumorspheres of CSCs (ALDHhigh cells).
See this image and copyright information in PMC

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