Non-invasive Physical Plasma Modulates Macrophage Polarization: A Potential Strategy for Tumor Microenvironment Remodeling.

BACKGROUND/AIM: Non-invasive physical plasma (NIPP) has shown promise in the treatment of cancer. However, conflicting results have been reported regarding the effect of NIPP on macrophage polarization. As tumor-associated macrophages (TAMs) are essential in the regulation of cancer development, this study aimed to determine the role of NIPP treatment in macrophage polarization and tumor-microenvironment (TME) remodeling. MATERIALS AND METHODS: A portable NIPP device, Plasma Care (Terraplasma Medical, Garching, Germany), was employed as the source of NIPP. The human monocytic cell line THP-1 was adopted as the cell model for macrophage differentiation and polarization. The effects of NIPP treatment on temperature, pH value, and oxidative stress induction of the culture medium were examined to validate the feasibility of applying the NIPP device in subsequent cell treatment. The changes in morphology, viability, and proliferation of THP-1 cells after NIPP treatment were determined. The expression of M1/M2 macrophage markers was examined by real-time quantitative polymerase chain reaction. RESULTS: No significant changes were observed in temperature and pH value after NIPP treatment, while the formation of hydrogen peroxide was promoted in a time-dependent manner. Cell morphology, viability, and proliferation were not affected by up to 6 minutes of NIPP treatment. In monocytes, 6 minutes of NIPP treatment significantly increased the expression of M1 markers (TNF-α and IL-6) and suppressed the M2 marker (CD206), findings which were consistent in the monocyte-derived macrophages. Furthermore, NIPP treatment also significantly promoted M1 polarization in the monocyte-derived macrophages induced by phorbol 12-myristate 13-acetate. CONCLUSION: NIPP is a safe and robust oxidative stress inducer and showed potential in TAM regulation by promoting M1 macrophage polarization.

Linc00673-V3 positively regulates autophagy by promoting Smad3-mediated LC3B transcription in NSCLC.

Since its first discovery, long noncoding RNA Linc00673 has been linked to carcinogenesis and metastasis of various human cancers. Linc00673 had five transcriptional isoforms and their biological functions remained to be explored. Here we have reported that Linc00673-V3, one of the isoforms of Linc00673, promoted non-small cell lung cancer chemoresistance, and increased Linc00673-V3 expression level was associated with enhanced autophagy. Mechanistically, we discerned the existence of a stem-loop configuration engendered by the 1-100-nt and 2200-2275-nt fragments within Linc00673-V3. This structure inherently interacted with Smad3, thereby impeding its ubiquitination and subsequent degradation orchestrated by E3 ligase STUB1. The accumulation of Smad3 contributed to autophagy via up-regulation of LC3B transcription and ultimately conferred chemoresistance in NSCLC. Our results revealed a novel transcriptional regulation network between Linc00673-V3, Smad3, and LC3B, which provided an important insight into the interplay between autophagy regulation and non-canonical function of Smad3. Furthermore, the results from in vivo experiments suggested Linc00673-V3 targeted antisense oligonucleotide as a promising therapeutic strategy to overcome chemotherapy resistance in NSCLC.

Modulation of the Tumor-Associated Immuno-Environment by Non-Invasive Physical Plasma.

Over the past 15 years, investigating the efficacy of non-invasive physical plasma (NIPP) in cancer treatment as a safe oxidative stress inducer has become an active area of research. So far, most studies focused on the NIPP-induced apoptotic death of tumor cells. However, whether NIPP plays a role in the anti-tumor immune responses need to be deciphered in detail. In this review, we summarized the current knowledge of the potential effects of NIPP on immune cells, tumor-immune interactions, and the immunosuppressive tumor microenvironment. In general, relying on their inherent anti-oxidative defense systems, immune cells show a more resistant character than cancer cells in the NIPP-induced apoptosis, which is an important reason why NIPP is considered promising in cancer management. Moreover, NIPP treatment induces immunogenic cell death of cancer cells, leading to maturation of dendritic cells and activation of cytotoxic CD8+ T cells to further eliminate the cancer cells. Some studies also suggest that NIPP treatment may promote anti-tumor immune responses via other mechanisms such as inhibiting tumor angiogenesis and the desmoplasia of tumor stroma. Though more evidence is required, we expect a bright future for applying NIPP in clinical cancer management.

Extracellular Vesicle-Packaged circATP2B4 Mediates M2 Macrophage Polarization via miR-532-3p/SREBF1 Axis to Promote Epithelial Ovarian Cancer Metastasis.

Ovarian cancer is one of the most common gynecologic malignancies with a highly immunosuppressive tumor microenvironment (TME) and poor prognosis. Circular RNA (circRNA) is a type of noncoding RNA with high stability, which has been shown to play an important role in biological processes and TME reprogramming in a variety of tumors. The biological function of a novel circRNA, circATP2B4, in epithelial ovarian cancer (EOC) was detected and evaluated. Transmission electron microscopy, differential ultracentrifugation and qRT-PCR were used to verify the existence of extracellular vesicles (EV)-packaged circATP2B4. Macrophage uptake of circATP2B4 was determined by EVs tracing. Dual luciferase reporter, FISH, Western blotting, and flow cytometry assays were used to investigate the interactions between circATP2B4 and miR-532-3p as well as sterol regulatory element-binding factor 1 (SREBF1) expression in macrophages. CircATP2B4 was upregulated in EOC tissues and positively correlated with ovarian cancer progression. Functionally, circATP2B4 promoted carcinogenic progression and metastasis of EOC both in vitro and in vivo. Mechanistically, EV-packaged circATP2B4 in EOC could be transmitted to infiltrated macrophages and acted as competing endogenous RNA of miR-532-3p to relieve the repressive effect of miR-532-3p on its target SREBF1. Furthermore, circATP2B4 induced macrophage M2 polarization by regulating the miR-532-3p/SREBF1/PI3Kα/AKT axis, thereby leading to immunosuppression and ovarian cancer metastasis. Collectively, these data indicate that circATP2B4-containing EVs generated by EOC cells promoted M2 macrophages polarization and malignant behaviors of EOC cells. Thus, targeting EVs-packaged circATP2B4 may provide a potential diagnosis and treatment strategy for ovarian cancer.

The Role of Perineural Invasion in Prostate Cancer and Its Prognostic Significance.

Perineural invasion (PNI) is a common indication of tumor metastasis that can be detected in multiple malignancies, including prostate cancer. In the development of PNI, tumor cells closely interact with the nerve components in the tumor microenvironment and create the perineural niche, which provides a supportive surrounding for their survival and invasion and benefits the nerve cells. Various transcription factors, cytokines, chemokines, and their related signaling pathways have been reported to be important in the progress of PNI. Nevertheless, the current understanding of the molecular mechanism of PNI is still very limited. Clinically, PNI is commonly associated with adverse clinicopathological parameters and poor outcomes for prostate cancer patients. However, whether PNI could act as an independent prognostic predictor remains controversial among studies due to inconsistent research aim and endpoint, sample type, statistical methods, and, most importantly, the definition and inclusion criteria. In this review, we provide a summary and comparison of the prognostic significance of PNI in prostate cancer based on existing literature and propose that a more standardized description of PNI would be helpful for a better understanding of its clinical relevance.

Identification of metastasis-related long non-coding RNAs in lung cancer through a novel tumor mesenchymal score.

Long non-coding RNAs (lncRNAs) have been proven to play critical roles in epithelial-mesenchymal transition (EMT) and metastasis of lung cancer. However, the biological functions and related mechanisms of lncRNAs are unclear. In addition, the EMT-based prognosis prediction in lung cancer still lacks investigation. Here, we established the methodology of identifying critical metastasis-related lncRNAs using comprehensive datasets of cancer transcriptome, genome and epigenome, and also provided tools for prognosis prediction in lung cancer. Initially, important mesenchymal marker genes were identified to compose the tumor mesenchymal score, which predicted patient prognosis in lung cancer, especially lung adenocarcinoma (LUAD). The score was also correlated with several crucial biological and physiological processes, such as tumor immune and hypoxia. Based on the score, lung cancer patients was classified into epithelial and mesenchymal subtypes, and lncRNAs which exhibited expressional dysregulation, promotor methylation alteration and copy number variation between the two subtypes in LUAD were identified and underwent further prognostic analyses. Finally, we identified 14 lncRNAs as EMT-related and significant biomarkers in prognosis prediction of LUAD. As validation, lncRNA RBPMS-AS1 was proven to be co-expressed with epithelial biomarkers, suppressive for A549 cell migration, invasion and EMT, and also significantly associated with better outcomes of LUAD patients, suggesting the potential of RBPMS-AS1 to serve as a lncRNA epithelial biomarker in metastasis of LUAD. Based on the identified lncRNAs, an EMT-linked lncRNA prognostic signature was further established. Taken together, our study provides robust predictive tools, potential lncRNA targets and feasible screening strategies for future study of lung cancer metastasis.

LncRNA CASC15, MiR-23b Cluster and SMAD3 form a Novel Positive Feedback Loop to promote Epithelial-Mesenchymal Transition and Metastasis in Ovarian Cancer.

Cancer Susceptibility Candidate 15 (CASC15), which is a newly identified long noncoding RNA crucial for epigenetic regulation in human tumors, was found to be associated with poor prognosis of the patients with ovarian cancer by utilizing The Cancer Genome Atlas and Gene Expression Omnibus database. Therefore, the purpose of this paper was to explore the functional role and latent molecular mechanism of CASC15 in the progression of ovarian cancer. In vitro and in vivo experiments validated CASC15 as an oncogenic lncRNA in ovarian cancer, which could enhance metastasis through TGF-ß-induced epithelial-mesenchymal transition progress. MiR-23b-3p and miR-24-3p, which are members of the miR-23b cluster, were identified to directly target CASC15 through luciferase assays. Further mechanistic investigations indicated that CASC15-mediated miR-23b-3p/miR-24-3p sequestration cooperatively upregulated SMAD3 expression, which, in turn, would permit increased CASC15 mRNA level as a transcription activation factor. This study first described a miR-23b-3p/miR-24-3p-mediated positive feedback loop between CASC15 and SMAD3, which may reflect the underlying molecular mechanism of CASC15's oncogenic function in ovarian cancer.

Impact of antitumor regimens on the outcomes of cancer patients with COVID-19: a pooled analysis.

Since the outbreak of coronavirus disease 2019 (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) discovered in December 2019, the disease has emerged as a global pandemic (Shi et al., 2020; World Health Organization, 2020). Several studies have shown a higher incidence of COVID-19, as well as related poor outcomes in patients with malignancies as compared with those without them (Liang et al., 2020; Tian et al., 2020). The impact of cancer on COVID-19 may be attri­buted to the use of antitumor treatments that may disturb the host response to SARS-CoV-2 infection (Wang et al., 2020), while the current studies on this topic have drawn controversial conclusions. Some implied that anticancer treatments might elevate the risk of death (García-Suárez et al., 2020; Liu et al., 2020). On the contrary, others pointed out that this association is not significant (Brar et al., 2020; Lee et al., 2020a). Although previous systematic reviews have investigated this important issue (Wang and Huang, 2020), the heterogeneity of findings is obvious and the general conclusion has remained unclear. Considering this ambiguity, it is difficult for clinicians to make therapeutic decisions when facing patients with both cancer and COVID-19; therefore, a high-quality and accurate evaluation of the impact of anticancer treatments on COVID-19 patients is necessary. Accordingly, we conducted a pooled analysis with the original data of each patient for the first time to provide a comprehensive perspective into the association between anticancer regimens and the outcomes of cancer patients with COVID-19.

Low-dose mono(2-ethylhexyl) phthalate promotes ovarian cancer development through PPARα-dependent PI3K/Akt/NF-κB pathway.

The plasticizer di(2-ethylhexyl) phthalate (DEHP) and its hydrolysate mono(2-ethylhexyl) phthalate (MEHP) are major toxicants from plastics, but their association with hormone-dependent cancers has been controversial. We treated the human ovarian cancer cell lines SKOV3 and A2780 with low concentrations of DEHP/MEHP, and found that although no significant effect on cell proliferation was observed, ovarian cancer cell migration, invasion, and epithelial-mesenchymal transition (EMT) were promoted by submicromolar MEHP but not DEHP. Next, ovarian cancer patient data from The Cancer Genome Atlas (TCGA) were obtained and subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) supported enrichment and Kaplan-Meier survival analyses, which identified PI3K/Akt pathway as a pivotal signaling pathway in ovarian cancer. We found that 500 nM MEHP treatment significantly increased PIK3CA expression, which could be reversed by the knockdown of peroxisome proliferator-activated receptor alpha (PPARα). Silencing PIK3CA significantly suppressed the MEHP-induced migration, invasion and EMT. In addition, we validated that MEHP treatment promoted phosphorylation of Akt and degradation of IκB-α, thereby activating NF-κB and enhancing NF-κB nuclear translocation. In nude mice, MEHP exposure significantly promoted the metastasis of ovarian cancer xenografts, which could be suppressed by the treatment of PPARα inhibitor GW6471. Our findings showed that low-dose MEHP promoted ovarian cancer progression through activating PI3K/Akt/NF-κB pathway, in a PPARα-dependent manner.

Driver and novel genes correlated with metastasis of non-small cell lung cancer: A comprehensive analysis.

Although mutations of genes are crucial events in tumorigenesis and development, the association between gene mutations and lung cancer metastasis is still largely unknown. The goal of this study is to identify driver and novel genes associated with non-small cell lung cancer (NSCLC) metastasis. Candidate genes were identified using a novel comprehensive analysis, which was based on bioinformatics technology and meta-analysis. Firstly, EGFR, KRAS, ALK, TP53, BRAF and PIK3CA were identified as candidate driver genes. Further meta-analysis identified that EGFR (Pooled OR 1.33, 95% CI 1.19, 1.50; P < .001) and ALK (Pooled OR 1.52, 95% CI 1.22, 1.89; P < .001) mutations were associated with distant metastasis of NSCLC. Besides, ALK (Pooled OR 2.40, 95% CI 1.71, 3.38; P < .001) mutation was associated with lymph node metastasis of NSCLC. In addition, thirteen novel gene mutations were identified to be correlated with NSCLC metastasis, including SMARCA1, GGCX, KIF24, LRRK1, LILRA4, OR2T10, EDNRB, NR1H4, ARID4A, PRKCI, PABPC5, ACAN and TLN1. Furthermore, elevated mRNA expression level of SMARCA1 and EDNRB was associated with poor overall survival in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), respectively. Additionally, pathway and protein-protein interactions network analyses found the two genes were correlated with epithelial-mesenchymal transition process. In conclusion, mutations of EGFR and ALK were significantly correlated with NSCLC metastasis. In addition, thirteen novel genes were identified to be associated with NSCLC metastasis, especially SMARCA1 in LUAD and EDNRB in LUSC.

How we assess the perioperative anxiety of surgical patients with pulmonary nodules: the revision of state-trait anxiety inventory.

PURPOSE: The aim of the study was to develop a short form of State-Trait Anxiety Inventory (STAI) and calculate the norms for the assessment of anxiety in surgical patients in mainland China. METHODS: Patients who were scheduled to carry out pulmonary surgery in our department were included. The sinicized 40-item STAI Form-Y was used to assess the anxiety on the surgery eve. Then the coefficient of variation, coefficient of correlation, stepwise regression analysis, principal component analysis, and structural equation model were successively to filter the items. The reliability and validity of the revised STAI was estimated and the norms were computed. RESULTS: 445 intact replies were collected. A 13-item STAI with 6 items in state subscale and 7 items in trait subscale produced similar scores with the full version of STAI. The Cronbach alpha coefficients for the state and trait subscales were 0.924 and 0.936, respectively. The determinant coefficients were 0.781 and 0.822, respectively. Moreover, the norms of both state subscale and trait subscale are provided according to the age and gender. CONCLUSIONS: The revised short form of STAI has good reliability and validity. It is likely to be more acceptable by reducing the fatigue effects, and is suitable for follow-up study on the assessment and intervention of perioperative anxiety of surgical patients with pulmonary nodules.

Identification of a Novel Prognostic Classification Model in Epithelial Ovarian Cancer by Cluster Analysis.

BACKGROUND: Heterogeneity plays an essential role in ovarian cancer. Patients with different clinical features may manifest diverse patterns in diagnosis, treatment, and prognosis. The aim of the present study was to identify a novel ovarian cancer-classification model through cluster analysis and assess its significance in prognosis. METHODS: Among patients diagnosed with ovarian cancer in the Women's Hospital School of Medicine, Zhejiang University between January 2014 and May 2019, 328 patients were included in a K-mean cluster analysis and 176 patients followed up. Major clinical indicators, overall survival, and recurrence-free survival in different subgroups were compared. RESULTS: Two clusters for ovarian cancer were identified and grouped as noninflammatory (n=247) and inflammatory subtypes (n=81). Compared with the noninflammatory subgroup, the inflammatory subgroup presented a statistically significantly higher level of median CRP (median (IQR) 20.4 [7.8-47.3] vs 1.2 [0.4-3.5], p<0.001), neutrophil percentage (median (IQR) 76.9 [72.6-81.3] vs 66.2 [61.0-72.0], p<0.001), leukocyte count (median (IQR) 8.9 [7.0-10.0] vs 6.0 [5.1-7.2], p<0.001), fibrinogen (median (IQR) 5.0 [4.4-6.0] vs 3.4 [2.9-3.9], p<0.001), and platelet count (median (IQR) 324 [270-405] vs 229 [181.5-269], p<0.001). During a median follow-up of 52 months, 21 participants (16.3%) died in the noninflammatory group, while 14 (29.8%) died in the inflammatory group (HR 2.15, 95% CI 1.09-4.23; p=0.024). Death/recurrence was observed in 38 (29.5%) patients from the noninflammatory group and 25 (53.2%) from the inflammatory group (HR 2.32, 95% CI 1.40-3.85; p<0.001). CONCLUSION: Our study revealed a novel classification model of ovarian cancer that features inflammation. Inflammation predicts shorter survival and poorer prognosis, suggesting the significance of inflammation in the management of ovarian cancer.

[Prognostic Risk Factors for Patients Receiving Airway Stent Placement].

BACKGROUND: Airway stents are used to treat central airway stenosis or tracheal fistula caused by a variety of malignant and benign tracheal diseases as well as iatrogenic procedures. Airway stent placement has a satisfying effect in instantly relieving of symptoms, but the long-term survival of patients still depends on the individualized treatment of the primary diseases. Therefore, exploring the prognostic risk factors of patients who received airway stent placement can be beneficial to the optimization of the placement procedure and also the improvement of individualized clinical management of patients. METHODS: Data of a total of 66 patients who underwent airway stent placement at the First Affiliated Hospital of Zhejiang University from January 2014 to June 2017 were retrospectively collected. Prognostic effects of the clinical characteristics as age, gender, Charlson comorbidity index (CCI) and procedure duration were analyzed. RESULTS: Age and gender had no significant effect on the outcomes of the patients, while higher CCI (P=0.045) and procedure duration over 60 min (P=0.037) were both independent risk factors of poor prognosis. A prognostic nomogram was then constructed, of which the area under the curve of the receiver operating characteristic (ROC) curve and the concordance index (C-index) was 0.71 and 0.69, respectively. CONCLUSIONS: For patients receiving airway stent placement, the baseline CCI and the procedure duration had prognostic significance in clinical practice.

Benzo(a)pyrene regulated A549 cell migration, invasion and epithelial-mesenchymal transition by up-regulating long non-coding RNA linc00673.

As a major toxicant which is abundant in tobacco smoking, benzo(a)pyrene (BaP) is considered as a strong carcinogen of lung cancer. In spite of the intensive research, the role that BaP plays in lung cancer still lacks a comprehensive and precise understanding. Recently, a long non-coding RNA, linc00673, has emerged as a central player in different kinds of malignancies, including non-small cell lung cancer (NSCLC). In the present study, we found that BaP with the concentration of no more than 8 µM did not affect cell proliferation in the NSCLC cell line A549, while it significantly enhanced A549 cell migration and invasion. Further results revealed that BaP promoted mesenchymal biomarkers expression and inhibited the major epithelial biomarker E-cadherin in a time and dose dependent manner, which indicated epithelial-mesenchymal transition (EMT) was induced by BaP in A549 cells. Through quantitative real-time PCR, we observed that BaP significantly elevated the expression level of linc00673. While after the knockdown of aryl hydrocarbon receptor (AHR), the up-regulating effect of BaP on linc00673 was reversed. Furthermore, silencing linc00673 significantly suppressed the BaP-induced migration, invasion, and EMT in A549 cells. In summary, our study demonstrates that BaP promotes A549 cell migration, invasion and EMT through up-regulating the expression of linc00673 in an AHR-dependent manner.

A Novel Scoring System for Pivotal Autophagy-Related Genes Predicts Outcomes after Chemotherapy in Advanced Ovarian Cancer Patients.

BACKGROUND: In the clinical practice of ovarian cancer, the application of autophagy, an important regulator of carcinogenesis and chemoresistance, is still limited. This study aimed to establish a scoring system based on expression profiles of pivotal autophagy-related (ATG) genes in patients with stage III/IV ovarian cancer who received chemotherapy. METHODS: Data of ovarian serous cystadenocarcinoma in The Cancer Genome Atlas (TCGA-OV) were used as training dataset. Two validation datasets comprised patients in a Chinese local database and a dataset from the Gene Expression Omnibus (GEO). ATG genes significantly (P < 0.1) associated with overall survival (OS) were selected and aggregated into an ATG scoring scale, of which the abilities to predict OS and recurrence-free survival (RFS) were examined. RESULTS: Forty-three ATG genes were selected to develop the ATG score. In TCGA-OV, patients with lower ATG scores had better OS [HR = 0.41; 95% confidence interval (CI), 0.26-0.65; P < 0.001] and RFS [HR = 0.47; 95% CI, 0.27-0.82; P = 0.007]. After complete or partial remission to primary therapy, the rate of recurrence was 47.2% in the low-score group and 68.3% in the high-score group (odds ratio = 0.42; 95% CI, 0.18-0.92; P = 0.03). Such findings were verified in the two validation datasets. CONCLUSIONS: We established a novel scoring system based on pivotal ATG genes, which accurately predicts the outcomes of patients with advanced ovarian cancer after chemotherapy. IMPACT: The present ATG scoring system may provide a novel perspective and a promising tool for the development of personalized therapy in the future.

Myricetin inhibits NLRP3 inflammasome activation via reduction of ROS-dependent ubiquitination of ASC and promotion of ROS-independent NLRP3 ubiquitination.

Myricetin is a plant-derived flavonoid that exhibits diverse pharmacological properties. The NLRP3 (NLR family, pyrin domain-containing 3 protein) inflammasome is a cytosolic multiprotein complex that plays a critical role in the innate immune response and pathogenesis of multiple inflammatory disorders. The present study found that myricetin inhibited NLRP3 inflammasome assembly via promotion of reactive oxygen species (ROS)-independent ubiquitination of NLRP3 and reduction of ROS-dependent ubiquitination of ASC (apoptosis-associated speck-like protein containing a CARD), which disrupted the interaction between ASC and NLRP3 and inhibited ASC oligomerization. This effect was further confirmed in vivo using mouse models of lipopolysaccharide (LPS)-induced sepsis and alum-induced peritonitis. These results suggest the therapeutic value of myricetin by targeting NLRP3-driven inflammatory diseases.

The role of epithelial-mesenchymal transition in the post-lung transplantation bronchiolitis obliterans.

BACKGROUND: Many patients who receive lung transplantation (LT) operations develop varying degrees of bronchiolitis obliterans (BO) after the surgeries. Epithelial-mesenchymal transition (EMT) is considered to be related to the process of bronchiolitis obliterans. In this study we simulated the pathological process of post-lung transplantation bronchiolitis obliterans, and explored the correlation between BO and EMT of small airway epithelial cells. METHODS: We transplanted the left lungs of F344 rats to Lewis rats by the Tri-cuff anastomosis and established the allogeneic rat left lung orthotopic transplantation model. Cyclosporine and lipopolysaccharide were administrated appropriately after the surgery. The histological structure and the expression levels of the EMT markers was observed with the methods of HE staining, Masson staining and immunohistochemistry. The analysis of enumeration data was performed using Fisher's Exact test and Spearman's rank correlation was used for the correlation analysis. RESULTS: Inflammatory cell infiltration, fibroplasia of bronchiole walls and significant lumen stenosis were found in the pulmonary mesenchyme of the transplanted lungs. The positive expression rate of E-cadherin in the transplanted lungs was 38.50% (5/13), significantly lower than that in the normal lung tissues [87.50% (7/8)] (P < 0.05), while the positive expression rate of Vimentin was 76.92% (10/13) which is significantly higher than that in the normal lung tissues [25.00% (2/8)] (P < 0.05). And a negative correlation existed between the expression levels of E-cadherin and Vimentin (r = -0.750, P < 0.01). CONCLUSIONS: In the disease model we established in this study, we found pathological changes that met BO characteristics happened in the transplanted lungs. Meanwhile, the small airway epithelial cells of transplanted lungs underwent an epithelial-mesenchymal transition, which indicated a role of EMT in the BO airway remodeling.