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.