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PPC is associated with a high frequency of postoperative relapse, and shows resistance to chemotherapy. The high malignancy of cancers is associated with genomic instability, which is related to mutations of tumor suppressor genes, such as tumor protein p53 (<jats:italic>TP53<\/jats:italic>) and ataxia-telangiectasia mutated (<jats:italic>ATM<\/jats:italic>). In addition, signaling pathways involving the oncogenes such as phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (<jats:italic>PIK3CA<\/jats:italic>) and epidermal growth factor receptor (<jats:italic>EGFR<\/jats:italic>) are associated with resistance to chemotherapy. However, the association of PPC with these gene mutations remains unknown. We investigated the impact of <jats:italic>TP53<\/jats:italic>, <jats:italic>ATM<\/jats:italic>, <jats:italic>PIK3CA<\/jats:italic>, and <jats:italic>EGFR<\/jats:italic> mutations on the postoperative prognosis of PPC.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Fifty-five patients with PPC who underwent complete resection were studied. A gene mutation analysis was performed using next-generation sequencing. Postoperative overall survival of patients with gene mutations was evaluated using a multivariable Cox proportional hazards model in which the explanatory variables were the presence of each gene mutation, and the confounding factors were pathological stage and age. The robustness of the results was evaluated by a sensitivity analysis.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The frequencies of pathogenic mutations in <jats:italic>TP53<\/jats:italic>, <jats:italic>ATM<\/jats:italic>, <jats:italic>PIK3CA<\/jats:italic>, and <jats:italic>EGFR<\/jats:italic> were 47, 0, 7, and 9%, respectively. A multivariable analysis adjusted for pathological stage and age showed a significant difference for only <jats:italic>PIK3CA<\/jats:italic> mutations. The hazard ratio (HR) for overall survival in cases with pathogenic mutations of <jats:italic>PIK3CA<\/jats:italic> for wild type or non-pathogenic mutations was 4.5 (95% confidence interval [CI] 1.1\u201318.8). Likewise, sensitivity analyses adjusted for pathological stage and sex (HR, 7.5; 95% CI 1.7\u201332.4) and for age and sex (HR, 5.4; 95% CI 1.4\u201321.7) resulted in similar findings. Although three patients with pathogenic mutations of <jats:italic>PIK3CA<\/jats:italic> that recurred postoperatively were treated by chemotherapy or immunotherapy, they survived for less than 2 years.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>The postoperative prognosis of PPC with <jats:italic>PIK3CA<\/jats:italic> pathogenic mutations is particularly poor. Pathogenic mutations of <jats:italic>PIK3CA<\/jats:italic> may be a postoperative prognostic marker. Inhibition of signaling pathways associated with <jats:italic>PIK3CA<\/jats:italic> mutations may also be a target for chemotherapy after relapse of PPC.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12885-022-10176-4","type":"journal-article","created":{"date-parts":[[2022,10,15]],"date-time":"2022-10-15T22:02:27Z","timestamp":1665871347000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["PIK3CA mutations associated with a poor postoperative prognosis in patients with pulmonary pleomorphic carcinoma: a retrospective cohort study"],"prefix":"10.1186","volume":"22","author":[{"given":"Kensuke","family":"Kojima","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saki","family":"Imai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hironobu","family":"Samejima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayako","family":"Fujiwara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiteru","family":"Tokunaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyungeun","family":"Yoon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoichi","family":"Okishio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,10,15]]},"reference":[{"issue":"1","key":"10176_CR1","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/S0272-5231(03)00061-3","volume":"23","author":"WD Travis","year":"2002","unstructured":"Travis WD. 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The Institutional Review Board of KCMC waived the requirement for informed consent from all research participants due to the retrospective and anonymous nature of this study. Information about opting out of the study was provided on the homepage of KCMC.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no conflicts of interest to in association with the present study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1066"}}