{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T23:43:41Z","timestamp":1788997421548,"version":"build-2803163510"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T00:00:00Z","timestamp":1738195200000},"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. Oncol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>To investigate the prognostic factors for stage IIb and IIIa lung adenocarcinoma following radical surgery and to explore the molecular mechanisms underlying these prognostic markers, focusing on the role of PIK3C2G.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A retrospective analysis of patients with stage IIb or IIIa lung adenocarcinoma who underwent radical surgery between January 2017 and June 2023 was conducted. Baseline clinical and pathological data, surgical methods, and postoperative treatments were analyzed to assess overall survival (OS). Univariate and multivariate Cox regression analyses were conducted to identify prognostic factors. Whole-exome sequencing (WES) was performed on a subset of the patients with preserved tumor tissues and no matched targeted therapies to identify high-frequency mutated genes. Functional experiments in A549 lung adenocarcinoma cells were performed to evaluate the role of the significant genes in tumor progression through cell proliferation, migration, invasion, apoptosis, and cell cycle assays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The survival analysis of 877 stage IIb and IIIa lung adenocarcinoma cases revealed significant differences in clinical characteristics and outcomes. Stage IIb patients had a median OS of 58 months compared to 37 months for stage IIIa, with 5-year OS rates of 46.9% and 30.5%, respectively. Univariate and multivariate Cox regression identified pathological stage, number of positive lymph nodes, age, and targeted therapy as independent prognostic factors. WES of 184 patients with no matched targeted therapies revealed high-frequency mutations in genes such as TP53 and PIK3C2G, with the latter emerging as the most significant prognostic marker. Functional assays demonstrated that the knockdown of PIK3C2G in A549 cells significantly reduced proliferation, migration and invasion while promoting apoptosis and disrupting cell cycle progression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>PIK3C2G was identified as a significant prognostic marker in stage IIb and IIIa lung adenocarcinoma, with functional data supporting its therapeutic potential. Taken together, this study integrates clinical and molecular findings, which could be used as a reference to guide personalized treatment strategies.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2024.1473437","type":"journal-article","created":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T05:10:46Z","timestamp":1738213846000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Prognostic determinants and functional role of PIK3C2G in stage IIb-IIIa lung adenocarcinoma: insights from clinical and molecular analyses"],"prefix":"10.3389","volume":"14","author":[{"given":"Chao","family":"Gao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuehan","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiayao","family":"Diao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeye","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanqing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,1,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA: A Cancer J Clin"},{"key":"B2","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.jtho.2015.09.009","article-title":"The IASLC lung cancer staging project: proposals for revision of the TNM stage groupings in the forthcoming (eighth) edition of the TNM classification for lung cancer","volume":"11","author":"Goldstraw","year":"2016","journal-title":"J Thorac Oncol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3779\/j.issn.1009-3419.2023.102.18","article-title":"Updated interpretation of the NCCN clinical practice guidelines (Version 3. 2023) for non-small cell lung cancer [in chinese","volume":"26","author":"Zhu","year":"2023","journal-title":"Zhongguo Fei Ai Za Zhi"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1200\/JOP.2016.013052","article-title":"Treatment of stage IIIA non\u2013small-cell lung cancer: A concise review for the practicing oncologist","volume":"12","author":"Santana-Davila","year":"2016","journal-title":"JOP"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdy275","article-title":"Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"29","author":"Planchard","year":"2018","journal-title":"Ann Oncol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.5306\/wjco.v8.i1.1","article-title":"Therapeutic management options for stage III non-small cell lung cancer","volume":"8","author":"Yoon","year":"2017","journal-title":"World J Clin Oncol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21338","article-title":"Cancer statistics in China, 2015","volume":"66","author":"Chen","year":"2016","journal-title":"CA Cancer J Clin"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1080\/14737140.2021.1913785","article-title":"Factors associated with early lung cancer mortality: A systematic review","volume":"21","author":"Goussault","year":"2021","journal-title":"Expert Rev Anticancer Ther"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.21037\/tlcr.2020.03.40","article-title":"Epidemiology of stage III lung cancer: frequency, diagnostic characteristics, and survival","volume":"10","author":"Casal-Mouri\u00f1o","year":"2021","journal-title":"Transl Lung Cancer Res"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2014.04.007","article-title":"Predictors of survival for younger patients less than 50 years of age with non-small cell lung cancer (NSCLC): a California Cancer Registry analysis","volume":"85","author":"Lara","year":"2014","journal-title":"Lung Cancer"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.chest.2020.11.028","article-title":"Sex and survival after surgery for lung cancer: A swedish nationwide cohort","volume":"159","author":"Sachs","year":"2021","journal-title":"Chest"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1378\/chest.130.6.1796","article-title":"Women with pathologic stage I, II, and III non-small cell lung cancer have better survival than men","volume":"130","author":"Cerfolio","year":"2006","journal-title":"Chest"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.cllc.2015.12.013","article-title":"Risk factors for local and distant recurrence after surgical treatment in patients with non-small-cell lung cancer","volume":"17","author":"Dziedzic","year":"2016","journal-title":"Clin Lung Cancer"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1378\/chest.09-1378","article-title":"Classification of the thoroughness of mediastinal staging of lung cancer","volume":"137","author":"Detterbeck","year":"2010","journal-title":"Chest"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.athoracsur.2008.07.076","article-title":"The significance of one-station N2 disease in the prognosis of patients with nonsmall-cell lung cancer","volume":"86","author":"Misthos","year":"2008","journal-title":"Ann Thorac Surg"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.13.9030","article-title":"Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE Collaborative Group","volume":"26","author":"Pignon","year":"2008","journal-title":"J Clin Oncol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2017.04.003","article-title":"Plasma ctDNA analysis for detection of the EGFR T790M mutation in patients with advanced non-small cell lung cancer","volume":"12","author":"Jenkins","year":"2017","journal-title":"J Thorac Oncol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2019.08.027","article-title":"Brigatinib vs crizotinib in patients with ALK inhibitor-naive advanced ALK+ NSCLC: Updated results from the phase III ALTA-1L trial","volume":"14","author":"Camidge","year":"2019","journal-title":"J Thorac Oncol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdz131","article-title":"Crizotinib in ROS1-rearranged advanced non-small-cell lung cancer (NSCLC): updated results, including overall survival, from PROFILE 1001","volume":"30","author":"Shaw","year":"2019","journal-title":"Ann Oncol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/s1470-2045(16)30562-9","article-title":"Cabozantinib in patients with advanced RET-rearranged non-small-cell lung cancer: an open-label, single-centre, phase 2, single-arm trial","volume":"17","author":"Drilon","year":"2016","journal-title":"Lancet Oncol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/s1470-2045(16)30146-2","article-title":"Dabrafenib plus trametinib in patients with previously treated BRAF(V600E)-mutant metastatic non-small cell lung cancer: an open-label, multicentre phase 2 trial","volume":"17","author":"Planchard","year":"2016","journal-title":"Lancet Oncol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0910672106","article-title":"Genetic diagnosis by whole exome capture and massively parallel DNA sequencing","volume":"106","author":"Choi","year":"2009","journal-title":"Proc Natl Acad Sci USA"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdw005","article-title":"Clinical correlation of extensive-stage small-cell lung cancer genomics","volume":"27","author":"Dowlati","year":"2016","journal-title":"Ann Oncol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1021\/cb1001476","article-title":"Lung cancer-genomics and personalized medicine","volume":"5","author":"Mahapatra","year":"2010","journal-title":"ACS Chem Biol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.jbiotec.2019.05.005","article-title":"TP53, EGFR and PIK3CA gene variations observed as prominent biomarkers in breast and lung cancer by serum cell-free DNA genomic testing","volume":"300","author":"Savli","year":"2019","journal-title":"J Biotechnol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-04135-5","article-title":"The CLIP1-LTK fusion is an oncogenic driver in nonsmall-cell lung cancer","volume":"600","author":"Izumi","year":"2021","journal-title":"Nature"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1080\/0284186X.2018.1433322","article-title":"Associations between primary tumor RAS, BRAF and PIK3CA mutation status and metastatic site in patients with chemo-resistant metastatic colorectal cancer","volume":"57","author":"Christensen","year":"2018","journal-title":"Acta Oncol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinexpmed.2015.02.003","article-title":"PIK3C2G copy number is associated with clinical outcomes of colorectal cancer patients treated with oxaliplatin","volume":"8","author":"Li","year":"2015","journal-title":"Int J Clin Exp Med"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1136\/esmoopen-2018-EACR25.5","article-title":"PIK3C2G loss promotes pancreatic cancer through MTOR regulation and metabolic rewiring","volume":"8","author":"Santis","year":"2018","journal-title":"ESMO Open"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1080\/21655979.2021.2020549","article-title":"Repressing phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma by microRNA-142-3p restrains the progression of hepatocellular carcinoma","volume":"13","author":"Zeng","year":"2022","journal-title":"Bioengineered"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2015.06.168","article-title":"miR-502 inhibits cell proliferation and tumor growth in hepatocellular carcinoma through suppressing phosphoinositide 3-kinase catalytic subunit gamma","volume":"464","author":"Chen","year":"2015","journal-title":"Biochem Biophys Res Commun"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-14-3303","article-title":"Manic fringe promotes a claudin-low breast cancer phenotype through notch-mediated PIK3CG induction","volume":"75","author":"Zhang","year":"2015","journal-title":"Cancer Res"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.2478\/acph-2019-0004","article-title":"The antitumor activity of umbelliferone in human renal cell carcinoma via regulation of the p110gamma catalytic subunit of PI3Kgamma","volume":"69","author":"Wang","year":"2019","journal-title":"Acta Pharm"},{"key":"B34","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.canlet.2018.10.035","article-title":"Genomic sequencing and editing revealed the GRM8 signaling pathway as potential therapeutic targets of squamous cell lung cancer","volume":"442","author":"Zhang","year":"2019","journal-title":"Cancer Lett"},{"key":"B35","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1164\/rccm.201902-0294OC","article-title":"Genomic underpinnings of tumor behavior in in situ and early lung adenocarcinoma","volume":"201","author":"Qian","year":"2020","journal-title":"Am J Respir Crit Care Med"},{"key":"B36","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1186\/s13000-023-01349-1","article-title":"Molecular profiling and prognostic biomarkers in Chinese non-small cell lung cancer cohort","volume":"18","author":"Shen","year":"2023","journal-title":"Diagn Pathol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1093\/neuros\/nyaa471","article-title":"Differences in genomic alterations between brain metastases and primary tumors","volume":"88","author":"Dono","year":"2021","journal-title":"Neurosurgery"},{"key":"B38","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1186\/s12885-022-09597-y","article-title":"Gene alternation of cerebrospinal fluid in patients with leptomeningeal metastases of lung adenocarcinoma using next-generation sequencing","volume":"22","author":"Yang","year":"2022","journal-title":"BMC Cancer"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1534\/g3.120.401128","article-title":"A genome-wide screen in mice to identify cell-extrinsic regulators of pulmonary metastatic colonisation","volume":"10","author":"van der Weyden","year":"2020","journal-title":"G3"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1007\/s10528-024-10788-4","article-title":"Overexpression of PIK3CG in cancer cells promotes lung cancer cell migration and metastasis through enhanced MMPs expression and neutrophil recruitment and activation","volume":"8","author":"Sun","year":"2024","journal-title":"Biochem Genet"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2024.1473437\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T05:10:53Z","timestamp":1738213853000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2024.1473437\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,30]]},"references-count":40,"alternative-id":["10.3389\/fonc.2024.1473437"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2024.1473437","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,30]]},"article-number":"1473437"}}