{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T09:33:14Z","timestamp":1787045594559,"version":"build-2736575974"},"reference-count":33,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Incomplete microwave ablation (iMWA) of lung cancer often leads to rapid recurrence and metastasis, yet the underlying mechanisms remain unclear. This study explored whether iMWA promotes tumor progression by activating the cyclic GMP\u2013AMP synthase\u2013stimulator of interferon genes (cGAS\u2013STING) signaling pathway and its downstream effector ZEB1 in tumor cells. Materials and Methods: An in vivo iMWA model was established in nude mice bearing H1650 lung tumors, and an in vitro sublethal heat treatment model was used to mimic incomplete ablation. Transcriptomic profiling, molecular assays and functional analyses assessed cellular behavior and signaling activity changes post-iMWA; genetic and pharmacologic interventions modulated STING signaling and autophagy. Results: Post-iMWA residual cells exhibited enhanced proliferation and invasion. Thermal injury induced necrosis and inhibited mitophagy, causing cytosolic mtDNA accumulation that activated the intrinsic cGAS\u2013STING pathway. This upregulation of ZEB1 drove epithelial\u2013mesenchymal transition and dissemination. Notably, silencing STING or ZEB1, or pharmacologically restoring autophagy, significantly suppressed tumor growth and metastasis. Conclusions: iMWA drives malignant progression of lung cancer through an mtDNA\u2013cGAS\u2013STING\u2013ZEB1 signaling axis. Targeting this pathway\u2014by inhibiting STING or enhancing autophagy\u2014may represent a promising therapeutic strategy to mitigate recurrence and metastasis following microwave ablation.<\/jats:p>","DOI":"10.3390\/cancers18162594","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T07:57:26Z","timestamp":1786521446000},"page":"2594","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Residual Lung Cancer After Incomplete Microwave Ablation Exhibits cGAS\u2013STING\u2013ZEB1-Driven Malignant Progression"],"prefix":"10.3390","volume":"18","author":[{"given":"Chuanfei","family":"Zhan","sequence":"first","affiliation":[{"name":"Department of Critical Care Unit, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing 210000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Zhai","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing 210000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianming","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Nanjing Drum Tower Hospital, Drum Tower Clinical Medical College, Nanjing Medical University, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaokang","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Thoracic and Cardiovascular Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing 210000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuliang","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Critical Care Unit, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing 210000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shilin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing 210000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1158\/1055-9965.EPI-19-0221","article-title":"Cancer progress and priorities: Lung cancer","volume":"28","author":"Schabath","year":"2019","journal-title":"Cancer Epidemiol. 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