Lin T, Jiang SC, He XM, Xu WZ, Jin CJ, Guo YD. Expression of cancer stem cell markers and their prognostic significance in stage IIIA non-small cell lung cancer. World J Stem Cells 2025; 17(9): 106381 [DOI: 10.4252/wjsc.v17.i9.106381]
Corresponding Author of This Article
You-Dan Guo, Department of Respiratory Disease, Jiangxi Provincial People’s Hospital, No. 92 Aiguo Road, Nanchang 330006, Jiangxi Province, China. 13970945069@163.com
Research Domain of This Article
Oncology
Article-Type of This Article
Retrospective Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Tao Lin, Wen-Zhen Xu, Cai-Jin Jin, Department of Cardio-Thoracic Surgery, Sanmen People’s Hospital, Sanmen 317100, Zhejiang Province, China
Si-Cong Jiang, Department of Thoracic and Endocrine Surgery, University Hospitals and University of Geneva, Geneva 450000, Switzerland
Xian-Ming He, Department of Oncology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
You-Dan Guo, Department of Respiratory Disease, Jiangxi Provincial People’s Hospital, Nanchang 330006, Jiangxi Province, China
Author contributions: Lin T and Jiang SC prepared the figures; Lin T, Jiang SC, Jin CJ, and Guo YD wrote and improved the main manuscript; He XM and Xu WZ contributed to revision of the main manuscript text and prepared the table; Jin CJ and Guo YD contributed to supervision and replied to review comments; All authors read and approved the final manuscript.
Institutional review board statement: This study was approved by the Medical Ethics Committee of the First Affiliated Hospital of Nanchang Medical College (approval number: FA240011).
Informed consent statement: Informed consent to participate was obtained from all participants in the study.
Conflict-of-interest statement: All authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Received: March 21, 2025 Revised: May 16, 2025 Accepted: August 4, 2025 Published online: September 26, 2025 Processing time: 187 Days and 11.3 Hours
Abstract
BACKGROUND
Non-small cell lung cancer (NSCLC) is the most prevalent subtype of lung cancer, accounting for approximately 85% of all lung cancer cases and remaining a major cause of cancer-related mortality worldwide. Despite advances in diagnostic and therapeutic approaches, the incidence and mortality rates of NSCLC continue to rise, especially in low-income and middle-income countries.
AIM
To investigate the expression of cancer stem cell (CSC) markers and their relationship with the prognosis and survival of patients with stage IIIA NSCLC.
METHODS
A retrospective analysis was conducted on the clinical data and survival follow-up information of 61 patients with stage IIIA NSCLC treated at our hospital from February 2020 to June 2022, and all cases were confirmed as primary (non-recurrent) diagnoses based on clinical and pathological records. All patients were followed up through outpatient visits or telephone interviews. The follow-up duration ranged from 6 to 51 months with a median follow-up time of 36 months. Overall survival (OS) was defined as the time from the date of pathological diagnosis to death or the last follow-up. Univariate and multivariate Cox regression analyses were performed to examine the relationship between clinical characteristics and OS. Immunohistochemistry was used to detect the expression of CSC markers [octamer-binding transcription factor 4 (OCT4), trophoblast cell surface antigen-2 (TROP-2), ATP-binding cassette subfamily G member 2 (ABCG2), p75 neurotrophin receptor (p75NTR)] in NSCLC, followed by immunohistochemical scoring. The high H-scores of CSC markers, age, and micropapillary components were combined to generate a tumor stemness index (TSI). The Kaplan-Meier method was used to analyze the relationship between CSC markers, TSI, and OS in patients with NSCLC.
RESULTS
Multivariate Cox regression analysis showed that age [hazard ratio (HR) = 1.952, 95% confidence interval (CI): 1.087-2.481, P = 0.029] and micropapillary components (HR = 2.716, 95%CI: 1.259-5.837, P = 0.013) were significantly associated with OS. In NSCLC there were 21 cases with high OCT4 H-scores, 27 cases with high TROP-2 H-scores, 44 cases with high ABCG2 H-scores, and 44 cases with high p75NTR H-scores. In the survival analysis the high OCT4 expression group had a poorer prognosis (P = 0.006). Further subtype analysis revealed no statistically significant difference in OS between high and low OCT4 H-score groups in patients with lung squamous cell carcinoma (P = 0.457). However, in patients with lung adenocarcinoma high OCT4 expression had significantly poorer OS compared with those with low OCT4 expression (P = 0.005). TROP-2, ABCG2, and p75NTR did not significantly affect the prognosis. TSI was significantly associated with OS in patients with NSCLC (HR = 2.209, 95%CI: 1.238-3.681, P = 0.027).
CONCLUSION
Age and micropapillary components were related to OS in patients with stage IIIA NSCLC. High expression of OCT4 and high TSI were associated with poor prognosis.
Core Tip: In patients with stage IIIA non-small cell lung cancer, older age and the presence of micropapillary components were significantly associated with worse overall survival, indicating their potential role in risk stratification. Furthermore, high expression of octamer-binding transcription factor 4 and elevated mRNA expression-based stemness index, both markers of tumor stemness, were closely linked to poor prognosis. These factors may serve not only as important prognostic indicators but also as potential therapeutic targets, contributing to more personalized and effective treatment strategies in clinical practice.
