Though invasive mucinous adenocarcinoma of the lung (IMA) is pathologically distinctive, the molecular mechanism driving IMA is not well understood, which hampers efforts to identify therapeutic targets. Here, by analyzing gene expression profiles of human and mouse IMA, we identified a Mucinous Lung Tumor Signature of 143 genes, which was unexpectedly enriched in mucin‐producing gastrointestinal, pancreatic, and breast cancers. The signature genes included transcription factors FOXA3, SPDEF, HNF4A, mucins MUC5AC, MUC5B, MUC3, and an inhibitory immune checkpoint VTCN1 / B7‐H4 (but not PD‐L1 / B7‐H1 ). Importantly, induction of FOXA3 or SPDEF along with mutant KRAS in lung epithelium was sufficient to develop benign or malignant mucinous lung tumors, respectively, in transgenic mice. FOXA3 and SPDEF induced MUC5AC and MUC5B, while HNF4A induced MUC3 in human mucinous lung cancer cells harboring a KRAS mutation. ChIP‐seq combined with CRISPR/Cas9 determined that upstream enhancer regions of the mucin genes MUC5AC and MUC5B , which were bound by SPDEF, were required for the expression of the mucin genes. Here, we report the molecular signature and gene regulatory network driving mucinous lung tumors.

The purpose of this study was to evaluate the factors contributing to the outcomes of bronchoplasty for lung cancer by analysing a single institution's data for a 30-year period. A retrospective review of 213 patients who underwent bronchoplasty for lung cancer between 1980 and 2010 was undertaken. The patients were divided into two groups by the date of surgery: the first period was 1980–95, and the second period was 1996–2010. Bronchoplasty and broncho-angioplasty were performed in 100 (75.8%) and 32 (24.2%) patients, respectively, in the first period and 61 (75.3%) and 20 (24.7%) patients, respectively, in the second period. Overall 90-day operative morbidity and mortality rates were 25.8 and 9.8%, respectively, in the first period and 45.7 and 2.5%, respectively, in the second period. Thirty-day mortality rates were 6.8% in the first period and 0% in the second period. Five-year survival was 41.1% ( n = 132) in the first period and 61.5% ( n = 81) in the second period ( P = 0.0003). Comparing bronchoplasty and broncho-angioplasty, the 5-year survival was 45.6 and 26.5%, respectively, in the first period ( P = 0.0048) and 60.9 and 62.1%, respectively, in the second period ( P = 0. 8131). Using multivariate analysis to identify potential prognostic factors, the type of operation (broncho-angioplasty), postoperative complications and histology (non-squamous cell carcinoma) were significant factors affecting survival in the first period, but none of the factors significantly affected survival in the second period. When the rates of pN2 or N3 histological type disease were compared in each period, the rate of pN2 or N3 disease in non-squamous cell carcinoma was 51.4% in the first period and 45.5% in the second period; both were significantly higher than in squamous cell carcinoma (31.6 and 16.9%, respectively; P = 0. 0365 and 0.0073). The present study suggests that progress in the preoperative staging system and perioperative medical management, as well as surgery, has contributed to current improvements in patients undergoing bronchoplasty and broncho-angioplasty. However, since nodal status in non-squamous cell carcinoma is not precisely evaluated before the operation, the indication for bronchoplasty should be considered carefully.

Objectives: To determine the use of the mucin proteins MUC5B and MUC5AC as prognosis markers for non-small cell lung cancer (NSCLC) carrying epidermal growth factor receptor ( EGFR ) mutations. Setting: Patients who underwent surgical resection at Nagasaki University Hospital and related facilities in Japan between June 1996 and March 2013. Participant: 159 Japanese patients (male: n=103; female: n=56) with NSCLC, who underwent surgical resection ( EGFR -mutant type: n=78, EGFR wild type: n=81). Results: Patients whose tumours expressed MUC5B had significantly longer overall survival and relapse-free survival compared to the MUC5B-negative patients with EGFR mutant NSCLC (p=0.0098 and p=0.0187, respectively). In patients with EGFR wild-type NSCLC, there was no association with MUC5B expression. MUC5AC expression was not different between EGFR mutant and wild-type NSCLC. Conclusions: Present findings indicate that MUC5B, but not MUC5AC, is a novel prognostic biomarker for patients with NSCLC carrying EGFR mutations but not for patients with NSCLC carrying wild-type EGFR .