{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T23:13:20Z","timestamp":1793056400842,"version":"4.5.0"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Microinvasive adenocarcinoma (MIA) represents an early stage of lung adenocarcinoma (LUAD), yet how the tumor microenvironment (TME) and cancer-associated fibroblast (CAF)-derived exosomes contribute to its progression remains unclear. We aimed to define the cellular ecosystem of MIA and to clarify the role of periostin (POSTN) and POSTN\n                      <jats:sup>+<\/jats:sup>\n                      CAF-derived exosomes in early LUAD progression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Single-cell RNA sequencing (scRNA-seq) and tissue-derived exosomal RNA sequencing were performed on four primary MIA lesions and matched adjacent lung tissues. Integrated analyses of scRNA-seq data, exosomal transcriptomes, the TCGA-LUAD cohort, and an independent LUAD tissue\/serum cohort were used to characterize POSTN expression and to evaluate its prognostic and diagnostic relevance. Primary MIA-associated POSTN\n                      <jats:sup>+<\/jats:sup>\n                      and POSTN\n                      <jats:sup>-<\/jats:sup>\n                      CAFs were isolated for exosome preparation, followed by co-culture experiments with LUAD cell lines and xenograft assays.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      scRNA-seq identified a malignant Cancer\u2013alveolar type II (Cancer-AT2) epithelial subset and multiple CAF subsets. Among these, POSTN\n                      <jats:sup>+<\/jats:sup>\n                      CAFs were enriched in MIA tissues and showed enhanced crosstalk with Cancer-AT2 cells through extracellular matrix (ECM)-related ligand\u2013receptor interactions. Tissue-derived exosomes contained 588 differentially expressed mRNAs, among which POSTN was markedly upregulated and showed the strongest association with fibroblast-related signatures. POSTN was predominantly expressed in fibroblasts across independent non-small cell lung cancer datasets and was elevated in LUAD tissues, tissue-derived exosomes, and serum exosomes, correlating with advanced stage, lymph node metastasis, and poor survival. Functionally, POSTN\n                      <jats:sup>+<\/jats:sup>\n                      CAF-derived exosomes promoted LUAD cell proliferation, migration, invasion, colony formation, and xenograft growth.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Exosomal POSTN derived from POSTN\n                      <jats:sup>+<\/jats:sup>\n                      CAFs may represent an important stromal mediator of MIA\/LUAD progression and a potential diagnostic and prognostic biomarker in early-stage LUAD.\n                    <\/jats:p>\n                  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