COL6A6 Downregulation and Stromal Remodeling as Predictors of an Aggressive Tumor Microenvironment in Lung Adenocarcinoma

Aim: Collagen type VI alpha 6 chain (COL6A6), a component of the extracellular matrix, has been implicated in the regulation of tumor growth and metastasis. This study aimed to investigate the relationship between stromal COL6A6 expression, desmoplasia, lymph node metastasis, and PD-L1 expression in lung adenocarcinoma.Material and Methods: Sixty-two cases with lung adenocarcinoma were retrospectively analyzed. Desmoplasia was categorized as mild/absent or marked based on histopathological evaluation. Immunohistochemical staining for COL6A6 was performed, and tumors were classified as negative or positive according to stromal staining patterns. PD-L1 (DAKO 22C3) expression was evaluated in available cases using the tumor proportion score.Results: Loss of stromal COL6A6 expression was observed in 66.1% (n=41) of tumors, whereas all adjacent normal lung tissues showed strong expression. A statistically significant inverse association was identified between COL6A6 expression and desmoplasia (p<0.001). Tumors with marked desmoplasia showed a higher frequency of lymph nodes. Similarly, lymph node metastasis was more frequent in COL6A6-negative tumors, although this difference did not reach statistical significance. PD-L1 positivity was more frequently observed in tumors with marked desmoplasia and in those lacking COL6A6 expression.Conclusion: COL6A6 expression is markedly downregulated in lung adenocarcinoma and shows an inverse association with desmoplasia. Loss of COL6A6 may reflect an aggressive tumor microenvironment and could be associated with increased PD-L1 expression. These findings suggest that COL6A6 may serve as a potential prognostic and predictive biomarker in lung adenocarcinoma, warranting further investigation in larger cohorts.