Expression of cancer stem cell markers and their prognostic significance in stage IIIA non-small cell lung cancer

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.

Keywords: Stage IIIA non-small cell lung cancer; Tumor stem cell markers; Tumor stemness index; Prognosis survival; Relationship

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.