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Abstract Background Studies have shown that long noncoding RNAs and N6-methyladenosine play important roles in gastric cancer. The purpose of this study was to determine the correlation and prognostic value of m6A-related lncRNAs and immune infiltration in gastric cancer. Methods We downloaded the clinically related information and RNA-Seq transcriptome data of gastric cancer patients from the TCGA database. Univariate Cox regression analysis and Pearson analysis were used to screen out m6A-related lncRNAs. Consensus cluster analysis was used to divide the sample into two clusters, and LASSO analysis and Cox regression analysis were used to construct a risk scoring model. Results A total of 25 lncRNA expression profiles were screened, and gastric cancer patients were divided into different subtypes. Cluster 2 had a better prognosis, but its stromal score, ESTIMATE score and immune score were low. Cluster 1 was rich in resting memory CD4 T cells, regulatory T cells, monocytes, and resting mast cells, and Cluster 2 was rich in activated memory CD4 T cells and follicular helper T cells. Thirteen lncRNAs were selected to construct a risk model, and the prognosis of gastric cancer patients in the high-risk group was poor. The expression of PD-L1 in tumours is significantly higher than that in normal tissues. Univariate and multivariate Cox regression analysis results showed that the overall survival rate was significantly related to stage and the risk score, which can be used as an independent prognostic factor. The results of the heatmap and scatter plot showed that clusters (P = 0.0045) and grade (G1–2, G3, P = 0.0037) were significantly related to prognosis. The relationship between the risk score and immune cell infiltration showed that memory B cells, resting dendritic cells, M0 macrophages, and M2 macrophages were positively correlated with the risk score, while resting mast cells, monocytes, activated NK cells, and follicular helper T cells were negatively correlated with the risk score. Conclusion The results of this study indicate that m6A-related lncRNAs may play an important role in the prognosis of gastric cancer patients and the tumour immune microenvironment and may provide help for the treatment of gastric cancer patients.

Histidine-rich glycoprotein (HRG) is a multifunctional plasma glycoprotein involved in the regulation of coagulation, fibrinolysis, and inflammation. Recently, decreased plasma levels of HRG at 72 hours after lung transplantation (LT) has been shown to be associated with severe primary graft dysfunction and decreased overall survival after LT. In this study, we investigated the effect of supplementary HRG treatment on lung ischemia-reperfusion injury (IRI) using a mouse hilar clamp model. Mice were divided into the four groups, including the sham-operated group, the IRI group with supplementation of PBS, human serum albumin, or HRG (the HRG group) (n=5 for each group). We assessed lung function, lung injury, pulmonary neutrophil infiltrations, lung cell apoptosis, and inflammatory mediator expression between the groups. Compared to the other groups, the HRG group had significantly better PaO 2 and significant attenuation of lung injury (Figure). In the HRG group, neutrophil infiltration and prevalence of apoptotis in the reperfused lung was significantly less than the other groups. Moreover, the expression of neutrophil-associated inflammatory mediators in the reperfused lung, including CXCL1, MIP-1α, MIP-1β, G-CSF, GM-CSF, IL-1β, IL-6, and IL-10, were significantly decreased in the HRG group. In this study, supplementary HRG treatment suppressed neutrophil-associated inflammatory responses and improved lung IRI in a mouse. HRG may be a potential therapeutic agent for lung IRI. [ABSTRACT FROM AUTHOR]

Donor-specific human leukocyte antigen (HLA) antibodies (DSA) are being recognized as a risk factor of acute rejection and chronic lung allograft dysfunction (CLAD). Re-transplantation (re-LTx) is the only treatment for CLAD, but the outcome could be limited especially in the sensitized patients. Some desensitization protocols were reportedly verified in a single center study basis, but yet to be standardized in DSA-positive lung transplantation (LTx). Herein, we report a case of successful lung re-LTx along with perioperative desensitization for a DQ DSA-positive recipient. A 10-year-old-man underwent living-donor single lobar LTx for pulmonary graft-versus-host disease after bone marrow transplant. Three years later, he developed antibody-mediated rejection due to de novo DSA. The mean fluorescence intensity of DQ4 exceeded 12000 which was persistent even after antibody targeted therapy, resulting in the development of bronchiolitis obliterans syndrome. He needed a mechanical ventilator, and temporary use of Extra-Corporeal Membrane Oxygenation. Following two-year waiting time, he eventually acquired an organ offer from a brain-dead donor and underwent re-LTx. The virtual crossmatch revealed the patient's preformed antibody to DQ4 was donor-specific, and flow cytometry crossmatch test for B cell was also positive. Thus, we performed two sessions of plasma exchanges (PLEX) with 1.5 volume of fresh frozen plasma preoperatively, and five sessions postoperatively. Subsequently, intravenous immune globulin (1 g/kg) and antithymocyte globulin (3mg/kg) was also given. Target trough level of tacrolimus was set in a usual manner. Mean fluorescence intensities for the DSAs were monitored at several times (pre PLEX, post all perioperative desensitization, and two months after re-LTx) and confirmed to be going down (DQ4; 12580, 7578, 6344). He developed a single episode of mild acute cellular rejection, but his postoperative course was almost uneventful and he is doing well 4 months after re-LTx and returns to his normal daily life. Although this case possessed multiple immunological risks including re-LTx and positive DQ-DSA, perioperative desensitization with the combination of multiple PLEXs, IVIG and antithymocyte globulin was effective. Careful monitoring of DSA is planned in the long term. [ABSTRACT FROM AUTHOR]

In Japan, there is an age limit to register for lung transplantation. For lung transplantations from a brain-dead donor, the age limit is 60 years for single lung transplantation and 55 years for bilateral lung transplantation. Currently, there is no clear age limit for lung transplantation from living donor, but most facilities set the age limit at 65 years or younger. At our facility, even if the patient is aged over 65 years, we evaluate the patient's organ function and activities of daily living to assess the suitability for transplantation. Herein, we report a case of successful living lobar lung transplantation in a 67-year-old recipient. The patient was a 67-year-old female with a history of auto peripheral-blood stem cell transplantation for Hodgkin's lymphoma 8 years ago. Four years prior to presentation, lung damage with dilated shadows was observed on computed tomography (CT) scan. The shadows were thought to be caused by graft versus host disease. One year ago, she contracted bacterial pneumonia, which led to worsening of respiratory function. Finally, she contracted bilateral pneumothorax and was referred to our hospital for lung transplantation. She was 66-year-old at the time of referral to our hospital, so lung transplantation from a brain-dead donor was not indicated. Preoperative examination revealed no major problems with operative tolerance. After preoperative examination with two potential living donors, we determined that lung transplantation was feasible. Bilateral lung transplantation from living donors was performed with cardio-pulmonary bypass assistance. The right lung graft was donated by her daughter, and the left lung graft was donated by her son. The total operation duration was 617 minutes. Ischemic time was 150 minutes in the right graft and 240 minutes in the left graft. On postoperative day 6, she developed acute rejection with frosted shadows and was treated with steroid pulse therapy. The length of ICU stay was 45 days. On postoperative day 116, the patient was discharged from the hospital. We successfully performed bilateral lung transplantation from living donors in an elderly recipient by careful evaluation of detailed perioperative management and current condition of recipient. Based on our experience, we discuss the outcomes of living lung transplantations in elderly recipients. [ABSTRACT FROM AUTHOR]

Background: Since lung transplant recipients (LTRs) exhibit low immunogenicity after two doses of SARS-CoV-2 mRNA vaccines, optimal vaccine strategies for SARS-CoV-2 are required in LTRs. This study aimed to investigate the efficacy and safety of the third and fourth doses of the SARS-CoV-2 mRNA vaccines in LTRs., Methods: We conducted a single-center study of 73 LTRs and 23 healthy controls (HCs). Participants received two-to-four doses of SARS-CoV-2 mRNA vaccines. The LTRs were divided into three groups based on the number of vaccine dose. IgG titers against SARS-CoV-2 spike protein were measured, and adverse events were assessed. Factors associated with humoral response were analyzed using univariate and multivariate analyses., Results: The Dose 4 group (n = 27) had a higher humoral response rate (P = 0.018) and higher levels of anti-SARS-CoV-2 IgG antibody (P = 0.04) than the Dose 2 group (n = 14). The Dose 3 group (n = 32) had lower humoral response rates (P = 0.005) and levels of anti-SARS-CoV-2 IgG antibody (P = 0.0005) than the HCs (n = 23) even after the same dose. Systemic adverse events were milder in the LTRs than in the HCs (P < 0.05). Increased number of vaccine dose was identified as a predictor of positive humoral response (P = 0.021)., Conclusion: Booster doses of SARS-CoV-2 mRNA vaccines may enhance humoral response with mild adverse events in LTRs. Repeated vaccination might be warranted for LTRs to prevent SARS-CoV-2 infection., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2024 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Purpose: Radiation pneumonitis (RP) is an obstacle for patients after surgery following induction chemoradiotherapy for locally advanced non-small cell lung cancer (LA-NSCLC). We performed a comparative analysis of the association between clinicopathological factors, including the neutrophil-to-lymphocyte ratio (NLR) and prognosis, in LA-NSCLC patients with or without RP during induction chemoradiotherapy followed by surgery., Methods: The subjects of this analysis were 168 patients undergoing trimodality therapy for LA-NSCLC between January, 1999 and May, 2019. Patients were divided into two groups: the RP group (n = 41) and the non-RP group (n = 127). We compared the clinicopathological factors including the NLR between the groups and analyzed the association between the NLR and prognosis., Results: The RP group had more patients with tumors located in the lower lobe, more bilobar resections, shorter operative times, no implementation of postoperative adjuvant chemotherapy, and a higher postoperative NLR than the non-RP group. There were no significant differences in serious postoperative complications and the prognosis. Patients with a low postoperative NLR had a significantly better prognosis in the non-RP group, and a trend toward a better prognosis even in the RP group., Conclusion: Postoperative NLR may be a useful prognostic factor, even for patients who suffer RP after trimodality therapy for LA-NSCLC., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Purpose: Bronchopleural fistula (BPF) is a serious complication of lung resection. To avoid BPF, the bronchial stump/anastomotic site is often covered with a flap of surrounding tissue. One risk factor for BPF is radical lung resection after induction chemoradiotherapy for lung cancer. We retrospectively reviewed our database to elucidate the characteristics of tissue flaps that prevent BPF., Methods: This retrospective study included 152 patients treated between 1999 and 2019. We examined the clinicopathological characteristics, including the type and thickness of the tissue flap used to cover the bronchial stump/anastomotic site, and postoperative complications, including BPF., Results: BPF occurred in 5 patients (3.3%). All 5 patients had complications that could have affected delayed wound healing, such as pneumonia. The covering tissue flap thickness was significantly greater in patients without BPF than in those who developed BPF (p = 0.0290). Additionally, the tissue flap thickness was significantly greater than in those with BPF (p = 0.0077), even in high-risk patients who developed pneumonia or radiation pneumonitis on the operative side within 6 months postoperatively., Conclusion: Perioperative management is crucial to avoid complications affecting the healing of the bronchial stump/anastomotic site, and the covering tissue flap thickness may be an important factor in avoiding or minimizing BPF., (© 2024. The Author(s).)

Background: Neutrophil-to-lymphocyte ratio (NLR) has been reported as a prognostic biomarker in non-small cell lung cancer (NSCLC); however, the underlying biological rationale remains unclear. The present study aimed to explore the potential utility of NLR as a surrogate biomarker for immune response to cancer and to elucidate the underlying mechanism., Methods: This retrospective study included the medical records of 120 patients with NSCLC who underwent surgery at the study institution in 2012. NLR in peripheral blood was determined from blood test within 30 days before surgery. Tumor immune status was evaluated using immunohistochemical staining to identify CD3+, CD8+ and FOXP3+ tumor-infiltrating lymphocytes (TILs), and the relationship of NLR, with clinicopathologic characteristics including 5-year overall survival (OS), and the tumor immune status was investigated. The median values of NLR and TIL count were used as cutoff points., Results: The 5-year OS was significantly better in patients with low NLR (<2.2) than in those with high NLR (≥2.2) (70.1% vs. 56.8%, P = 0.042) and in patients with high CD3+ TIL count (≥242) than in those with low CD3+ TIL count (<242) (70% vs. 56.8%, P = 0.019). Additionally, the CD3+ TIL count was negatively correlated with preoperative NLR (P = 0.005)., Conclusion: NLR might potentially reflect the immune status of tumor microenvironment, explaining its impact on prognosis of patients with NSCLC., (© The Author(s) 2024. Published by Oxford University Press.)

Doublecortin (DCX)-positive neural progenitor-like cells are purported components of the cancer microenvironment. The number of DCX-positive cells in tissues reportedly correlates with cancer progression; however, little is known about the mechanism by which these cells affect cancer progression. Here we demonstrated that DCX-positive cells, which are found in all major histological subtypes of lung cancer, are cancer-associated Schwann cells (CAS) and contribute to the chemoresistance of lung cancer cells by establishing an adrenergic microenvironment. Mechanistically, the activation of the Hippo transducer YAP/TAZ was involved in the acquisition of new traits of CAS and DCX positivity. We further revealed that CAS express catecholamine-synthesizing enzymes and synthesize adrenaline, which potentiates the chemoresistance of lung cancer cells through the activation of YAP/TAZ. Our findings shed light on CAS, which drive the formation of an adrenergic microenvironment by the reciprocal regulation of YAP/TAZ in lung cancer tissues., (© 2024 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Mechanisms underlying primary and acquired resistance to MET tyrosine kinase inhibitors (TKIs) in managing non-small cell lung cancer remain unclear. In this study, we investigated the possible mechanisms acquired for crizotinib in MET-amplified lung carcinoma cell lines. Two MET-amplified lung cancer cell lines, EBC-1 and H1993, were established for acquired resistance to MET-TKI crizotinib and were functionally elucidated. Genomic and transcriptomic data were used to assess the factors contributing to the resistance mechanism, and the alterations hypothesized to confer resistance were validated. Multiple mechanisms underlie acquired resistance to crizotinib in MET-amplified lung cancer cell lines. In EBC-1-derived resistant cells, the overexpression of SERPINE1, the gene encoding plasminogen activator inhibitor-1 (PAI-1), mediated the drug resistance mechanism. Crizotinib resistance was addressed by combination therapy with a PAI-1 inhibitor and PAI-1 knockdown. Another mechanism of resistance in different subline cells of EBC-1 was evaluated as epithelial-to-mesenchymal transition with the upregulation of antiapoptotic proteins. In H1993-derived resistant cells, MEK inhibitors could be a potential therapeutic strategy for overcoming resistance with downstream mitogen-activated protein kinase pathway activation. In this study, we revealed the different mechanisms of acquired resistance to the MET inhibitor crizotinib with potential therapeutic application in patients with MET-amplified lung carcinoma., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Shinichi Toyooka received research funding from Eli Lilly Japan, Taiho (Japan) and Chugai (Japan), and lecture fees from Chugai. All other authors have declared that no competing interests exist., (Copyright: © 2024 Thu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purposes: Robot-assisted thoracoscopic (RATS) segmentectomy is becoming increasingly common because of the expanded indications for segmentectomy and the widespread adoption of robotic surgery. The precise division of the intersegmental plane is necessary to ensure oncologic margins from the tumor and to preserve the lung function. In this study, we present a strategy for accurately dividing the intersegmental plane using a robotic stapler and review the surgical outcomes., Methods: RATS portal segmentectomy was performed using the Da Vinci Xi system and the intersegmental plane was dissected using a robotic stapler. We evaluated the perioperative outcomes in 92 patients who underwent RATS portal segmentectomy between May 2020 and January 2023. These results were compared with those of 82 patients who underwent complete video-assisted thoracoscopic surgery (CVATS) during the same period., Results: The operative and console times were 162 and 97 min, respectively. No intraoperative complications occurred, and postoperative complications were observed in four cases (4.3%). The operative time, blood loss, postoperative complications, and maximum incision size were significantly lower in the RATS group than in the CVATS group. However, RATS requires a significantly higher number of staplers than CVATS., Conclusions: The division of the intersegmental plane using a robotic stapler in RATS portal segmentectomy was, therefore, found to be safe and effective., (© 2024. The Author(s).)

Background: Living donor lobar lung transplantation is a life-saving procedure for critically ill patients. This requires 2 healthy donors exposed to risks and without medical benefit. Therefore, the donor's safety and minimal postoperative complications are crucial. This study aimed to investigate the short-term outcomes and identify the risk factors affecting these outcomes., Methods: The data of 175 living donors enrolled between 1998 and 2022 were analyzed. Donors were divided into era 1 (1998-2009) and era 2 (2010-2022)., Results: The overall incidence of postoperative complications was 39%, of which 7% were major complications. Donors who underwent surgery on the right side had a higher incidence of delayed pulmonary fistulae ( P  = 0.01) and elevated liver enzyme levels ( P  = 0.028). Living donor surgery on the right side ( P  = 0.01), era 2 ( P  = 0.01), and the need for plasty ( P  = 0.04) were predictors of postoperative complications., Conclusions: Updated data on complications and their correlation with postoperative quality of life from this study could aid in the selection of potential donors and facilitate informed consent., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2024 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Objectives: To clarify the impact of central nervous system (CNS) metastasis on performance status (PS) at relapse, on subsequent treatment(s), and on survival of patients with lung adenocarcinoma harboring common epidermal growth factor receptor (EGFR) mutation., Methods: We conducted the multicenter real-world database study for patients with radical resections for lung adenocarcinomas between 2015 and 2018 at 21 centers in Japan. EGFR mutational status was examined at each center., Results: Of 4181 patients enrolled, 1431 underwent complete anatomical resection for lung adenocarcinoma harboring common EGFR mutations. Three-hundred-and-twenty patients experienced disease relapse, and 78 (24%) had CNS metastasis. CNS metastasis was significantly more frequent in patients with conventional adjuvant chemotherapy than those without (30% vs. 20%, P = 0.036). Adjuvant chemotherapy did not significantly improve relapse-free survival at any pathological stage (adjusted hazard ratio for stage IA2-3, IB, and II-III was 1.363, 1.287, and 1.004, respectively). CNS metastasis did not affect PS at relapse. Subsequent treatment, mainly consisting of EGFR-tyrosine kinase inhibitors (TKIs), could be equally given in patients with or without CNS metastasis (96% vs. 94%). Overall survival after relapse was equivalent between patients with and without CNS metastasis., Conclusion: The efficacy of conventional adjuvant chemotherapy may be limited in patients with lung adenocarcinoma harboring EGFR mutations. CNS metastasis is likely to be found in practice before deterioration in PS, and may have little negative impact on compliance with subsequent EGFR-TKIs and survival after relapse. In this era of adjuvant TKI therapy, further prospective observational studies are desirable to elucidate the optimal management of CNS metastasis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: Chronic lung allograft dysfunction (CLAD) is a known long-term fatal disorder after lung transplantation. In this study, we evaluated the CLAD classification of the International Society for Heart and Lung Transplantation (ISHLT) for living-donor lobar lung transplantation (LDLLT)., Methods: We conducted a single-center retrospective review of data from 73 patients who underwent bilateral LDLLT between 1998 and 2019. Factors related to opacity on computed tomography (CT) and restriction on pulmonary function tests (PFTs) were also analyzed., Results: Overall, 26 (36%) patients were diagnosed with CLAD, including restrictive allograft syndrome (RAS), n = 10 (38.5%); bronchiolitis obliterans syndrome (BOS), n = 8 (30.8%); mixed, n = 1 (3.8%); undefined, n = 2 (7.7%); and unclassified, n = 5 (19.2%). The 5-year survival rate after the CLAD onset was 60.7%. The survival of patients with BOS was significantly better than that of patients with RAS (p = 0.012). In particular, patients with restriction on PFT had a significantly worse survival than those without restriction (p = 0.001)., Conclusions: CLAD after bilateral LDLLT does not have a major impact on the recipient survival, especially in patients with BOS. Restriction on PFT may predict a particularly poor prognosis in patients with CLAD after bilateral LDLLT., (© 2023. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Objectives: Histidine-rich glycoprotein has been reported as an anti-inflammatory glycoprotein that inhibits acute lung injury in mice with sepsis and as a prognostic biomarker in patients with sepsis. We investigated the relationship between plasma concentrations of histidine-rich glycoprotein and the risk of occurrence of primary graft dysfunction., Methods: According to the primary graft dysfunction grade at post-transplant 72 h, patients who underwent lung transplantation were divided into three groups: non-primary graft dysfunction group (grade 0-1), moderate primary graft dysfunction group (grade 2), and severe primary graft dysfunction group (grade 3). The plasma concentrations of histidine-rich glycoprotein measured daily during the first post-transplant 7 days were compared among the three groups. Appropriate cutoff values of the concentrations were set for survival analyses after lung transplantation., Results: A total of 68 patients were included. The plasma histidine-rich glycoprotein concentration at post-transplant 72 h was significantly lower in the severe primary graft dysfunction group (n = 7) than in the other two groups [non-primary graft dysfunction group (n = 43), P = 0.042; moderate primary graft dysfunction group (n = 18), P = 0.040]. Patients with plasma histidine-rich glycoprotein concentration ≥34.4 µg/ml at post-transplant 72 h had significantly better chronic lung allograft dysfunction-free survival (P = 0.012) and overall survival (P = 0.037) than those with the concentration <34.4 µg/ml., Conclusions: Plasma histidine-rich glycoprotein concentrations at post-transplant 72 h might be associated with the risk of development of primary graft dysfunction., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Background: In survivors of head and neck cancer (HNC), second primary lung cancer (SPLC) often develop as a result of a common risk factor, that is, smoking. A multicenter experience was reviewed to evaluate how the history of a diagnosis of HNC affects the outcomes of patients undergoing pulmonary resection for SPLC., Methods: A multicenter retrospective analysis of patients hospitalized between January 2012 and December 2018 was performed. From a cohort of 4521 patients undergoing therapeutic pulmonary resection for primary non-small cell lung cancer, 100 patients with a previous history of HNC (HNC group) were identified. These patients were compared with a control group consisting of 200 patients without an HNC history from the same cohort pair-matched with operating facility, age, sex, and pathologic stage of lung cancer., Results: At the time of surgery for SPLC, the HNC group showed malnutrition with a lower prognostic nutritional index compared with the control group (P < .001). The HNC group was determined to have postoperative complications more frequently (P = .02). The 5-year overall survival rates in the HNC and control groups were 59.0% and 83.2%, respectively (P < .001). Statistically, HNC history, lower prognostic nutritional index, squamous cell lung cancer, and TNM stage were identified to be independently associated with poor survival., Conclusions: Patients with SPLC after primary HNC often present with malnutrition and are predisposed to postoperative complications and poor survival after pulmonary resection., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Cancer-associated fibroblasts (CAFs) are important components in the tumor microenvironment, and we sought to identify effective therapeutic targets in CAFs for non-small cell lung cancer (NSCLC). In this study, we established fibroblast cell lines from the cancerous and non-cancerous parts of surgical lung specimens from patients with NSCLC and evaluated the differences in behaviors towards NSCLC cells. RNA sequencing analysis was performed to investigate the differentially expressed genes between normal fibroblasts (NFs) and CAFs, and we identified that the expression of periostin (POSTN), which is known to be overexpressed in various solid tumors and promote cancer progression, was significantly higher in CAFs than in NFs. POSTN increased cell proliferation via NSCLC cells' ERK pathway activation and induced epithelial-mesenchymal transition (EMT), which improved migration in vitro. In addition, POSTN knockdown in CAFs suppressed these effects, and in vivo experiments demonstrated that the POSTN knockdown improved the sensitivity of EGFR-mutant NSCLC cells for osimertinib treatment. Collectively, our results showed that CAF-derived POSTN is involved in tumor growth, migration, EMT induction, and drug resistance in NSCLC. Targeting CAF-secreted POSTN could be a potential therapeutic strategy for NSCLC. KEY MESSAGES: • POSTN is significantly upregulated in CAFs compared to normal fibroblasts in NCSLC. • POSTN increases cell proliferation via activation of the NSCLC cells' ERK pathway. • POSTN induces EMT in NSCLC cells and improves the migration ability. • POSTN knockdown improves the sensitivity for osimertinib in EGFR-mutant NSCLC cells., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)