Relationship Between The Stromal Cells And Tumor Spread Through Air Spaces In Lung Adenocarcinoma

Objective: The mechanism underlying tumor spread through air spaces(STAS)has not been well studied.Here,we investigated the role of tumor stromal cells in the pathogenesis of STAS from a pathological perspective and evaluated the prognostic significance of tumor stromal cells and STAS in postoperative patients with lung adenocarcinoma.Methods: We retrospectively analyzed 208 postsurgical patients with stage I–III lung adenocarcinoma.The presence of STAS was evaluated by hematoxylin and eosin staining,and the expression of α-SMA-positive cancer-associated fibroblasts(CAFs)and CD204-positive tumor-associated macrophages(TAMs)was analyzed by immunohistochemistry.A logistic regression model was applied to confirm the predictive factors of STAS.Survival analysis was performed to evaluate the effect of α-SMA-positiveCAFs,CD204-positive TAMs,and STAS on prognosis.A nomogram was generated to evaluate the prognosis of postoperative patients.Results: Logistic regression suggested that the expression of α-SMA-positive CAFs(p<0.001)and the number of CD204-positive TAMs(p<0.001)were related to the presence of STAS.The multivariate Cox proportional hazards model suggested that STAS(p=0.004),α-SMA-positive CAFs(p<0.001),and CD204-positive TAMs(p<0.001)were independent risk factors for prognosis.Harrell’s c-indexes for OS and RFS prediction based on nomograms were 0.84 [95% confidence interval(CI): 0.76–0.91] and 0.82(95% CI:0.76–0.89),respectively.Conclusions: The presence of STAS was associated with lung adenocarcinoma with high expression of α-SMA and CD204.Nomograms including STAS and stromal cells as variables are recommended as practical models to evalue the prognosis of lung adenocarcinoma patients.