Spatial transcriptome analysis of lung squamous cell carcinoma arising from interstitial pneumonia provides insights into tumor heterogeneity.

Abstract

Interstitial pneumonia (IP) is a refractory disease that causes severe inflammation and fibrosis in the interstitium of the lungs, often resulting in the development of lung cancer (LC) during treatment. Previous studies have demonstrated that the prognosis of LC complicated by IP is inferior to that of LC without IP. It is therefore of the utmost importance to gain a deeper understanding of the heterogeneity of such tumors. In the present study, we conducted spatial transcriptome analysis of squamous cell carcinoma arising from IP. The results suggested involvement of the glucocorticoid receptor pathway in treatment resistance. Immunostaining of squamous cell carcinoma specimens from patients with IP demonstrated that the tumors expressed NR3C1 to varying degrees. Furthermore, higher NR3C1 expression levels were associated with a significantly increased risk of recurrence. Our results point to a novel subtype of lung squamous cell carcinoma. Further analysis of the molecular mechanisms associated with this subtype may facilitate the development of novel diagnostic criteria and therapeutic approaches.