JAK2 Loss Arising From Tumor-Spread-Through-Air-Spaces (STAS) Promotes Tumor Progression by Suppressing CD8+ T Cells in Lung Adenocarcinoma: A Machine Learning Approach.

BACKGROUND: Tumor spread through air spaces (STAS) is a recently discovered risk factor for lung adenocarcinoma (LUAD). The aim of this study was to investigate specific genetic alterations and anticancer immune responses related to STAS. By using a machine learning algorithm and drug screening in lung cancer cell lines, we analyzed the effect of Janus kinase 2 (JAK2) on the survival of patients with LUAD and possible drug candidates. METHODS: This study included 566 patients with LUAD corresponding to clinicopathological and genetic data. For analyses of LUAD, we applied gene set enrichment analysis (GSEA), in silico cytometry, pathway network analysis, in vitro drug screening, and gradient boosting machine (GBM) analysis. RESULTS: The patients with STAS had a shorter survival time than those without STAS (P < 0.001). We detected gene set-related downregulation of JAK2 associated with STAS using GSEA. Low JAK2 expression was related to poor prognosis and a low CD8+ T-cell fraction. In GBM, JAK2 showed improved survival prediction performance when it was added to other parameters (T stage, N stage, lymphovascular invasion, pleural invasion, tumor size). In drug screening, mirin, CCT007093, dihydroretenone, and ABT737 suppressed the growth of lung cancer cell lines with low JAK2 expression. CONCLUSION: In LUAD, low JAK2 expression linked to the presence of STAS might serve as an unfavorable prognostic factor. A relationship between JAK2 and CD8+ T cells suggests that STAS is indirectly related to the anticancer immune response. These results may contribute to the design of future experimental research and drug development programs for LUAD with STAS.

Prognostic Analysis of Stage I Non-Small Cell Lung Cancer Abutting Adjacent Structures on Preoperative Computed Tomography.

Background: Early non-small cell lung cancer (NSCLC) that abuts adjacent structures requires careful evaluation due to its potential impact on postoperative outcomes and prognosis. We examined stage I NSCLC with invasion into adjacent structures, focusing on the prognostic implications after curative surgical resection. Methods: We retrospectively analyzed the records of 796 patients who underwent curative surgical resection for pathologic stage IA/IB NSCLC (i.e., visceral pleural invasion only) at a single center from 2008 to 2017. Patients were classified based on tumor abutment and then reclassified by the presence of visceral pleural invasion. Clinical characteristics, pathological features, and survival rates were compared. Results: The study included 181 patients with abutting NSCLC (22.7% of all participants) and 615 with non-abutting tumors (77.3%). Those with tumor abutment exhibited higher rates of non-adenocarcinoma (26.5% vs. 9.9%, p<0.01) and visceral/lymphatic/vascular invasion (30.4%/33.1%/12.7% vs. 8.5%/22.4%/5.7%, respectively; p<0.01) compared to those without abutment. Multivariable analysis identified lymphatic invasion and male sex as risk factors for overall survival (OS) and disease-free survival (DFS) in stage I NSCLC measuring 3 cm or smaller. Age, smoking history, vascular invasion, and recurrence emerged as risk factors for OS, whereas the presence of non-pure ground-glass opacity was a risk factor for DFS. Conclusion: NSCLC lesions 3 cm or smaller that abut adjacent structures present higher rates of various risk factors than non-abutting lesions, necessitating evaluation of tumor invasion into adjacent structures and lymph node metastasis. In isolation, however, the presence of tumor abutment without visceral pleural invasion does not constitute a risk factor.

Importance of Lymph Node Evaluation in ≤2-cm Pure-Solid Non-Small Cell Lung Cancer.

BACKGROUND: The prevalence of lymph node (LN) metastasis in small-sized lung cancer varies depending on the tumor size and proportion of ground-glass opacity. We investigated occult LN metastasis and prognosis in patients with small-sized non-small cell lung cancer (NSCLC), mainly focusing on the pure-solid tumor. METHODS: We retrospectively reviewed patients with ≤2-cm clinical N0 NSCLC who underwent lung resection with curative intent from 2003 to 2017. Among them we analyzed patients who also underwent adequate complete systematic LN dissection. Pathologic results and disease-free survival of the radiologically mixed ground-glass nodule (mGGN) and pure-solid nodule (PSN) groups were analyzed. RESULTS: Of 1329 patients analyzed, 591 had mGGNs and PSNs. As tumor size increased, patients in the mGGN group showed no difference in LN metastasis: ≤1 cm, 2.27%; 1.0 to 1.5 cm, 2.19%; and 1.5 to 2.0 cm, 2.18% (P = .999). However the PSN group showed a significant difference in LN metastasis as the tumor size increased: ≤1 cm, 2.67%; 1.0 to 1.5 cm, 12.46%; and 1.5 to 2.0 cm, 21.31% (P < .001). In the multivariate analysis tumor size was a significant predictor of nodal metastasis in the PSN group but not in the mGGN group. In terms of 5-year disease-free survival, the mGGN group showed a better prognosis than the PSN group (94.4% vs 71.2%, P < .001). CONCLUSIONS: We need to conduct a thorough LN dissection during surgery for small-sized NSCLC, especially for pure-solid tumors ≥ 1 cm.

Surgical outcomes and prognosis of non-small-cell lung cancer in patients with chronic lung diseases: a retrospective analysis.

OBJECTIVES: Lung cancer treatment in patients with chronic lung diseases is challenging because postoperative care is difficult and surgical outcomes are poorer than in patients with healthy lungs. This study aimed to examine postsurgical outcomes of patients with comorbid lung diseases treated for lung cancer. METHODS: This retrospective study enrolled 1526 patients who underwent curative surgical resection for non-small-cell lung cancer at a single centre between October 2008 and April 2017. Based on computed tomography findings, patients were assigned to 4 groups and their demographic characteristics, clinicopathological features, surgical outcomes and survival were compared. RESULTS: There were 1101 patients in group A, 266 patients in group B, 62 patients in group C and 97 patients in group D. In the chronic lung disease groups (B, C and D), there was a high percentage of smoking history (86.5%, 79.0% and 92.8%, respectively; P < 0.01). The occurrence rate of postoperative lung complications and operative mortality rates were higher in patients with chronic lung disease. Groups A, B, C and D contained 819 (74.4%), 159 (59.8%), 43 (69.4%) and 65 (67.0%) stage I patients, respectively (P < 0.01). The groups showed significant differences in overall survival and disease-free survival (all P < 0.01). The presence of combined pulmonary fibrosis and emphysema was the only significant negative prognostic factor for overall survival. CONCLUSIONS: The presence of comorbid chronic lung diseases might negatively affect prognosis in patients with non-small-cell lung cancer. The presence of combined pulmonary fibrosis and emphysema could be a negative prognostic factor in lung cancer treatment.

Complications after pectus excavatum repair using pectus bars in adolescents and adults: risk comparisons between age and technique groups.

OBJECTIVES: To compare the complications associated with age and technique groups in patients undergoing pectus excavatum (PE) repair. METHODS: The data of 994 patients who underwent PE repair from March 2011 to December 2015 were retrospectively reviewed. Mean age was 9.59 years (range 31 months-55 years), and 756 patients were men (76.1%). The age groups were defined as follows: Group 1, <5 years; Group 2, 5-9 years; Group 3, 10-14 years; Group 4, 15-17 years; Group 5, 18-19 years; Group 6, 20-24 years; and Group 7, >24 years. The technique groups were defined as follows: Group 1, patients who underwent repair with claw fixators and hinge plates; Group 2, patients who underwent repair with our 'bridge' technique. Complications were compared between age groups and technique groups. RESULTS: No cases of mortality occurred. Complication rates in the age groups 1-7 were 5.4%, 3.6%, 12.1%, 18.2%, 17.3%, 13.9% and 16.7%, respectively. The complication rate tripled after the age of 10. In multivariable analysis, odds ratio of Groups 4, 5 and 7 and asymmetric types were 3.04, 2.81, 2.97 and 1.70 (P < 0.01, P = 0.02, 0.03 and 0.03, respectively). The bar dislocation rate in technique Group 1 was 0.8% (6 of 780). No bar dislocations occurred in technique Group 2. CONCLUSIONS: Older patients have more asymmetric pectus deformity and they are also risk factors for complications following PE repair. The bridge technique provides a bar dislocation rate of 0%, even in adult patients. This procedure seems to reduce or prevent major complications following PE repair.