Lung adenocarcinoma: selection of surgical approaches in solid adenocarcinoma from the viewpoint of clinicopathologic features and tumor microenvironmental heterogeneity.

ABSTRACT

Introduction: Solid adenocarcinoma represents a notably aggressive subtype of lung adenocarcinoma. Amidst the prevailing inclination towards conservative surgical interventions for diminutive lung cancer lesions, the critical evaluation of this subtype's malignancy and heterogeneity stands as imperative for the formulation of surgical approaches and the prognostication of long-term patient survival. Methods: A retrospective dataset, encompassing 2406 instances of non-solid adenocarcinoma (comprising lepidic, acinar, and papillary adenocarcinoma) and 326 instances of solid adenocarcinoma, was analyzed to ascertain the risk factors concomitant with diverse histological variants of lung adenocarcinoma. Concurrently, RNA-sequencing data delineating explicit pathological subtypes were extracted from 261 cases in the TCGA database and 188 cases in the OncoSG database. This data served to illuminate the heterogeneity across lung adenocarcinoma (LUAD) specimens characterized by differential histological features. Results: Solid adenocarcinoma is associated with an elevated incidence of pleural invasion, microscopic vessel invasion, and lymph node metastasis, relative to other subtypes of lung adenocarcinoma. Furthermore, the tumor microenvironment (TME) in solid pattern adenocarcinoma displayed suboptimal oxygenation and acidic conditions, concomitant with augmented tumor cell proliferation and invasion capacities. Energy and metabolic activities were significantly upregulated in tumor cells of the solid pattern subtype. This subtype manifested robust immune tolerance and capabilities for immune evasion. Conclusion: This present investigation identifies multiple potential metrics for evaluating the invasive propensity, metastatic likelihood, and immune resistance of solid pattern adenocarcinoma. These insights may prove instrumental in devising surgical interventions that are tailored to patients diagnosed with disparate histological subtypes of LUAD, thereby offering valuable directional guidance.