Clinic information, pathological, and imaging characteristics in 2 058 surgical patients with lung cancer from a single center. / 单中心2 058ä¾‹è‚ºç™Œæ‰‹æœ¯æ‚£è€ çš„ä¸´åºŠä¿¡æ¯ã€ç— ç†åŠå½±åƒå­¦ç‰¹å¾.

OBJECTIVES: Lung cancer is characterized by its high incidence and case fatality rate. Factors related to population composition and cancer prevention programme policy have an effect on the incidence and diagnosis of lung cancer. This study aims to provide scientific support for early diagnosis and treatment of lung cancer by investigating the clinic information, pathological, and imaging characteristics of surgical patients with lung cancer. METHODS: The data of 2 058 patients, who underwent surgery for lung cancer in the Department of Thoracic Surgery of Xiangya Hospital of Central South University from 2016 to 2019, were retrospectively collected to analyze changes in clinic information, pathological, and imaging characteristics. RESULTS: From 2016 to 2019, the number of patients per year was 280, 376, 524, and 878, respectively. Adenocarcinoma (68.1%) was the most common pathological type of surgical patients with lung cancer. From 2016 to 2019, the proportion of adenocarcinoma was increased from 55.5% to 74.1%. The proportion lung cancer patients in stage IA was increased from 38.9% to 62.3%, and the proportion of patients who underwent sublobar resection was increased from 1.8% to 8.6%. The proportion of lymph node sampling was increased in 2019. Compared with the rate in 2016, the detection rate of nodules with diameter≤1 cm detected by CT before surgery in 2019 was significantly improved (2.0% vs 18.2%), and the detection rate of nodules with diameter>3 cm was decreased (34.7% vs 18.3%). From 2016 to 2019, the proportion of lesions with pure ground-glass density and partial solid density detected by CT was increased from 2.0% and 16.6% to 20.0% and 37.3%, respectively. The proportion of solid density was decreased from 81.4% to 42.7%. CONCLUSIONS: The number of lung cancer surgery patients is rapidly increasing year by year, the proportion of CT-detected purely ground-glass density and partially solid density lesions are increasing, the proportion of patients with adenocarcinoma is rising, the proportion of early-stage lung cancer is increasing, smaller lung cancers are detected in earlier clinical stage leading to a more minimally invasive approach to the surgical methods.

[A Case of New Rapidly Progressing Ground-glass Nodule Lung Adenocarcinoma Near Primary Lesion after Stereotactic Body Radiation Therapy].

Ground-glass nodule (GGN) lung cancer often progresses slowly in clinical and there are few clinical studies on long-term follow-up of patients with operable GGN lung cancer treated with stereotactic body radiation therapy (SBRT). We present a successful case of GGN lung cancer treated with SBRT, but a new GGN was found in the lung adjacent to the SBRT target during follow-up. The nodule progressed rapidly and was confirmed as lung adenocarcinoma by surgical resection. No significant risk factors and related driving genes were found in molecular pathological findings and genetic tests. It deserves further study whether new GGN is related to the SBRT. This case suggests that the follow-up after SBRT should be vigilant against the occurrence of new rapidly progressive lung cancer in the target area and adjacent lung tissue.
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LncRNA CALML3-AS1 modulated by m6A modification induces BTNL9 methylation to drive non-small-cell lung cancer progression.

Non-small cell lung cancer (NSCLC) is a common and lethal malignancy. The carcinogenic roles of lncRNA CALML3 antisense RNA 1 (CALML3-AS1) have been documented. However, the function and potential mechanisms of CALML3-AS1 in the progression of NSCLC need to be further explored. The molecule expression was assessed by qRT-PCR and Western blot. The subcellular localization of CALML3-AS1 was observed by fluorescence in situ hybridization (FISH). The malignant behaviors of NSCLC cells were evaluated by CCK-8, colony formation, EdU, wound healing and transwell assays. In vivo xenograft tumor and liver metastatic models were established. The molecular mechanisms were investigated by RIP, RNA pull-down and ChIP assays. The methylation level was detected by MSP. Herein, we found that CALML3-AS1 was upregulated, while butyrophilin-like 9 (BTNL9) was downregulated in NSCLC. Functionally, CALML3-AS1 depletion repressed NSCLC cell malignant phenotypes, in vivo tumor growth, and liver metastasis. Mechanistically, AlkB homolog 5 (ALKBH5) enhanced CALML3-AS1 stability via N6-methyladenosine (m6A) demethylation, whereas m6A reader YTH domain-containing 2 (YTHDC2) destabilized CALML3-AS1. Moreover, CALML3-AS1 inhibited BTNL9 transcription and expression through the recruitment of Zeste homolog 2 (EZH2). Rescue experiments demonstrated that BTNL9 downregulation counteracted sh-CALML3-AS1-mediated antitumor effects on NSCLC. Taken together, CALML3-AS1 modulated by ALKBH5 and YTHDC2 in an m6A modification dependent manner drives NSCLC progression via epigenetically repressing BTNL9.

Circadian gene ARNTL initiates circGUCY1A2 transcription to suppress non-small cell lung cancer progression via miR-200c-3p/PTEN signaling.

BACKGROUND: As a subclass of endogenous stable noncoding RNAs, circular RNAs are beginning to be appreciated for their potential as tumor therapeutics. However, the functions and mechanisms by which circRNAs exert protective functions in non-small cell lung cancer (NSCLC) remain largely elusive. METHODS: The prognostic role of circGUCY1A2 was explored in lung adenocarcinoma specimens. The overexpressed and knockdown plasmids were used to evaluate the effect of circGUCY1A2 on NSCLC cell proliferation and apoptosis efficacy. Luciferase reporter system is used to prove that circGUCY1A2 could bind to miRNA. Chip-PCR was used to prove that circGUCY1A2 could be initiated by transcription factors ARNTL. Subcutaneous tumorigenicity grafts models were established to validate findings in vivo. RESULTS: The expression of circGUCY1A2 were significantly reduced (P < 0.001) and negatively correlated with tumor size (P < 0.05) in non-small cell lung cancer (NSCLC). CircGUCY1A2 upregulation promoted apoptosis and inhibits cell proliferation and growth of subcutaneous tumorigenicity grafts in nude mice (P < 0.01). In addition, intra-tumor injection of pLCDH-circGUCY1A2 inhibited tumor growth in patient-derived NSCLC xenograft models (PDX). Mechanism studies showed that circGUCY1A2 could act as a sponge to competitively bind miR-200c-3p, promote PTEN expression, and thereby inhibit PI3K/AKT pathway. In addition, we found that the circadian gene ARNTL, which was reduced in NSCLC and prolonged the overall survival of patients, could bind to the promoter of circGUCY1A2, thereby increasing its expression. CONCLUSIONS: This study is an original demonstration that ARNTL can inhibit the development of lung adenocarcinoma through the circGUCY1A2/miR-200c-3p/PTEN axis, and this finding provides potential targets and therapeutic approaches for the treatment of lung adenocarcinoma.

Cuproptosis Depicts Immunophenotype and Predicts Immunotherapy Response in Lung Adenocarcinoma.

BACKGROUND: Although significant progress has been made in immunotherapy for lung adenocarcinoma (LUAD), there is an urgent need to identify effective indicators to screen patients who are suitable for immunotherapy. Systematically investigating the cuproptosis-related genes (CRGs) in LUAD may provide new ideas for patients' immunotherapy stratification. METHOD: We comprehensively analyzed the landscape of 12 CRGs in a merged TCGA and GEO LUAD cohort. We investigated the associations between tumor microenvironment and immunophenotypes. We utilized a risk score to predict the prognosis and immunotherapy response for an individual patient. Additionally, we conducted CCK-8 experiments to evaluate the impact of DLGAP5 knockdown on A549 cell proliferation. RESULT: We utilized an integrative approach to analyze 12 CRGs and differentially expressed genes (DEGs) in LUAD samples, resulting in the identification of two distinct CRG clusters and two gene clusters. Based on these clusters, we generated immunophenotypes and observed that the inflamed phenotype had the most abundant immune infiltrations, while the desert phenotype showed the poorest immune infiltrations. We then developed a risk score model for individual patient prognosis and immunotherapy response prediction. Patients in the low-risk group had higher immune scores and ESTIMATE scores, indicating an active immune state with richer immune cell infiltrations and higher expression of immune checkpoint genes. Moreover, the low-risk group exhibited better immunotherapy response according to IPS, TIDE scores, and Imvigor210 cohort validation results. In addition, our in vitro wet experiments demonstrated that DLGAP5 knockdown could suppress the cell proliferation of A549. CONCLUSION: Novel cuproptosis molecular patterns reflected the distinct immunophenotypes in LUAD patients. The risk model might pave the way to stratify patients suitable for immunotherapy and predict immunotherapy response.

Bioinformatics construction and experimental validation of a cuproptosis-related lncRNA prognostic model in lung adenocarcinoma for immunotherapy response prediction.

Cuproptosis is a newly form of cell death. Cuproptosis related lncRNA in lung adenocarcinoma (LUAD) has also not been fully elucidated. In the present study, we aimed to construct a prognostic signature based on cuproptosis-related lncRNA in LUAD and investigate its association with immunotherapy response. The RNA-sequencing data, clinical information and simple nucleotide variation of LUAD patients were obtained from TCGA database. The LASSO Cox regression was used to construct a prognostic signature. The CIBERSORT, ESTIMATE and ssGSEA algorithms were applied to assess the association between risk score and TME. TIDE score was applied to reflect the efficiency of immunotherapy response. The influence of overexpression of lncRNA TMPO-AS1 on A549 cell was also assessed by in vitro experiments. The lncRNA prognostic signature included AL606834.1, AL138778.1, AP000302.1, AC007384.1, AL161431.1, TMPO-AS1 and KIAA1671-AS1. Low-risk group exhibited much higher immune score, stromal score and ESTIMATE score, but lower tumor purity compared with high-risk groups. Also, low-risk group was associated with a much higher score of immune cells and immune related function sets, indicating an immune activation state. Low-risk patients had relative higher TIDE score and lower TMB. External validation using IMvigor210 immunotherapy cohort demonstrated that low-risk group had a better prognosis and might more easily benefit from immunotherapy. Overexpression of lncRNA TMPO-AS1 promoted the proliferation, migration and invasion of A549 cell line. The novel cuproptosis-related lncRNA signature could predict the prognosis of LUAD patients, and helped clinicians stratify patients appropriate for immunotherapy and determine individual therapeutic strategies.

Prognostic significance of tumor-associated macrophages polarization markers in lung cancer: a pooled analysis of 5105 patients.

BACKGROUND: The prognostic significance of tumor-associated macrophages (TAMs) in patients with lung cancer (LCa) remains controversial. We therefore conducted the present study to systematically evaluate the role of different TAMs markers and histologic locations on the prognosis of LCa. METHODS: Searches of Web of Science, PubMed, and EMBASE databases were performed up to 28 February 2022. The pooled analysis was conducted in random-effect or fixed-effects model with hazard risk (HR) and 95% confidence interval (CI) for survival data including overall survival (OS), and disease-free survival (DFS) from raw or adjusted measures, according to different TAMs markers and histologic locations. RESULTS: Including a total of 5105 patients from 30 eligible studies, the results indicated that the total count of CD68+ TAMs was negatively associated with OS and DFS, which was also observed in the relationship of CD68+ or CD204+ TAMs in tumor stroma (TS) with OS and DFS (all P<0.05). Conversely, higher CD68+ TAMs density in tumor nest (TN) or TN/TS ratio of CD68+ TAMs predicted better OS (all P<0.05). Similarly, higher HLA-DR+ TAMs density was correlated with better OS in TN and TS (all P<0.05). Besides, neither nest CD163+ TAM density nor stromal CD163+ TAM density was a prognostic factor in LCa patients (all P>0.05). CONCLUSION: Our study indicated that different TAMs markers and histologic locations could bring about different prognostic effects in LCa patients. Great understanding of the infiltration modes of TAMs may contribute to improve outcomes of LCa patients.

m6A methyltransferase METTL3-induced lncRNA SNHG17 promotes lung adenocarcinoma gefitinib resistance by epigenetically repressing LATS2 expression.

Gefitinib has been widely applied for the treatment of lung adenocarcinoma (LUAD). However, the long-term application of gefitinib usually leads to acquired drug resistance in tumour patients, resulting in clinical treatment failure. Small nucleolar host gene 17 (SNHG17) has been shown to play a regulatory role in LUAD progression. Nevertheless, the role of SNHG17 in LUAD gefitinib resistance remains elusive. The expression pattern of SNHG17 was examined in tissues and cell lines of gefitinib-sensitive and gefitinib-resistant LUAD, respectively. Gain- and loss-of-function experiments were employed to assess the biological functions of SNHG17 in cell proliferation and apoptosis, as well as aggressive phenotypes of LUAD cells. MeRIP-qPCR and colorimetric quantificational analysis were performed to detect m6A modifications and contents. Fluorescence in situ hybridisation (FISH) and subcellular fractionation analysis were used to reveal the distribution of SNHG17. RIP and ChIP assays were performed to further validate the SNHG17/EZH2/LATS2 regulatory axis. A xenograft tumour growth assay was conducted to evaluate the role of SNHG17 in LUAD gefitinib resistance in vivo. SNHG17 was upregulated in gefitinib-resistant LUAD tissues and cell lines. Functional assays showed that SNHG17 aggravated the malignant phenotypes of gefitinib-resistant LUAD cells. In addition, METTL3-mediated N6-methyladenosine modification could induce the upregulation of SNHG17by stabilising its RNA transcript. Mechanistically, SNHG17 epigenetically repressed the expression of LATS2 by recruiting EZH2 to the promoter region of LATS2. The regulatory role of the SNHG17/EZH2/LATS2 axis in LUAD gefitinib resistance was further supported in vivo. Collectively, our findings suggested that SNHG17 induced by METTL3 could promote LUAD gefitinib resistance by epigenetically repressing LATS2 expression.

GRP78 facilitates M2 macrophage polarization and tumour progression.

This study investigated the regulation of GRP78 in tumour-associated macrophage polarization in lung cancer. First, our results showed that GRP78 was upregulated in macrophages during M2 polarization and in a conditioned medium derived from lung cancer cells. Next, we found that knocking down GRP78 in macrophages promoted M1 differentiation and suppressed M2 polarization via the Janus kinase/signal transducer and activator of transcription signalling. Moreover, conditioned medium from GRP78- or insulin-like growth factor 1-knockdown macrophages attenuated the survival, proliferation, and migration of lung cancer cells, while conditioned medium from GRP78-overexpressing macrophages had the opposite effects. Additionally, GRP78 knockdown reduced both the secretion of insulin-like growth factor 1 and the phosphorylation of the insulin-like growth factor 1 receptor. Interestingly, insulin-like growth factor 1 neutralization downregulated GRP78 and suppressed GRP78 overexpression-induced M2 polarization. Mechanistically, insulin-like growth factor 1 treatment induced the translocation of GRP78 to the plasma membrane and promoted its association with the insulin-like growth factor 1 receptor. Finally, IGF-1 blockade and knockdown as well as GRP78 knockdown in macrophages inhibited M2 macrophage-induced survival, proliferation, and migration of lung cancer cells both in vitro and in vivo.

LncRNA UCC promotes epithelial-mesenchymal transition via the miR-143-3p/SOX5 axis in non-small-cell lung cancer.

Long non-coding RNAs (lncRNAs) have been found to play regulatory roles in cancers; for example, UCC was reported to promote colorectal cancer progression. However, the function of UCC in non-small-cell lung cancer (NSCLC) remains unclear. Therefore, mRNA and protein levels were assessed using qPCR and western blots. Cell viability was assessed by colony-formation assays. The interaction between lncRNAs and miRNAs was detected by dual-luciferase reporter and RIP assays. The tumorigenesis of NSCLC cells in vivo was determined by xenograft assays. LncRNA UCC was highly expressed in both NSCLC tissues and cells. Knockdown of UCC expression suppressed the proliferation of NSCLC cells. In addition, a dual-luciferase reporter system and RIP assays showed that UCC specifically bound to miR-143-3p and acted as a sponge of miR-143-3p in NSCLC cells. The miR-143-3p inhibitor rescued the inhibitory effect of sh-UCC on the proliferation of NSCLC cells. Moreover, miR-143-3p and UCC showed opposite effects on the expression of SOX5, which promoted EMT in NSCLC cells. In addition, in a mouse model, knockdown of UCC expression alleviated EMT and NSCLC progression in vivo, which was consistent with the in vitro results. In the current study, we found that UCC induced the proliferation and migration of NSCLC cells both in vitro and in vivo by inducing the expression of SOX5 via miR-143-3p and subsequently promoted EMT in NSCLC.

Comparison of Two Circular-Stapled Techniques for Esophageal Cancer: A Propensity-Matched Analysis.

OBJECTIVE: The optimal technique for the thoracoscopic construction of an intrathoracic esophagogastric anastomosis continues to be a subject of controversy. The aim of this study was to compare the perioperative outcomes of circular-stapled anastomosis using a transorally inserted anvil (Orvil™) with those of circular-stapled anastomosis using a transthoracically placed anvil (non-Orvil™) in totally minimally invasive Ivor Lewis esophagectomy (Ivor Lewis TMIE). METHODS: The data of 272 patients who underwent Ivor Lewis TMIE for esophageal cancer at multiple centers were collected from January 1, 2014 to December 31, 2017. After propensity score matching (1:1) for patient baseline characteristics, 65 paired cases were selected for statistical analysis. Logistic regression analysis was performed to investigate the significant factors of anastomotic leakage. RESULTS: In the propensity score-matched analysis, compared with the non-Orvil™ group, the Orvil™ group was associated with a significantly shorter operation time (p=0.031), less intraoperative hemorrhage (p<0.001), lower need for intraoperative transfusions (p=0.009), earlier postoperative oral feeding time (p=0.010), longer chest tube duration (p<0.001), shorter postoperative hospital stays (p=0.001), lower total hospitalization costs (p<0.001) and a lower postoperative anastomotic leakage rate (p=0.033). Multivariate logistic regression analysis showed that anastomotic technique and pulmonary infection were independent factors for the development of postoperative anastomotic leakage (p< 0.05). CONCLUSIONS: Orvil™ anastomosis exhibited better perioperative effects than non-Orvil™ anastomosis after the propensity score-matched analysis. Remarkably, the Orvil™ technique contributed to a lower postoperative anastomotic leakage rate than the non-Orvil™ technique.

Phenotypic analysis of tumor-infiltrating lymphocytes from non-small cell lung cancer and their potential application for adoptive cell therapy.

AIM: Adoptive cell therapy (ACT) of tumor-infiltrating lymphocytes (TILs) has demonstrated clinical benefits in metastatic melanoma treatment. However, the clinical application of TILs produced by a widely used standard protocol from non-small cell lung cancer (NSCLC) can be quite challenging because of the limited clinical benefits. A comprehensive phenotypic knowledge of TILs obtained from NSCLC is important for the development and improvement of personalized TIL therapy for NSCLC patients. METHODS: In this study, we successfully expanded TILs from 141 NSCLC tissues which can be used in clinical ACT after expansion by a rapid expansion protocol (REP). RESULTS: Our study indicates that the clinicopathological characteristics of patients have considerable impacts on the phenotype of in vitro TIL culture products. Different culture conditions are necessary for patients with different clinical features. Specific manipulations before REP expansion are required depending on the different phenotypes of TIL cultures (e.g. depletion of immune-suppressive γδT cells). With these optimizations, next-generation TIL therapy may become a treatment alternative for NSCLC patients in the future.

MICAL2 is a novel nucleocytoplasmic shuttling protein promoting cancer invasion and growth of lung adenocarcinoma.

MICAL2 is a tumor-promoting factor involved in cell migration, invasion, deformation, and proliferation not yet fully explored in lung adenocarcinoma (LUAD). This study demonstrated that MICAL2 was overexpressed and cytoplasm-enriched in LUAD tissues. Moreover, high cytoplasmic MICAL2 and/or total MICAL2 expression levels were positively correlated with lymphatic metastasis and shorter overall survival in LUAD patients. MICAL2 promoted LUAD cell proliferation, migration, invasion, and epithelial to mesenchymal transition-all of which involved the AKT and myosin-9 pathways. Furthermore, MICAL2 was identified as a nucleoplasm shuttling protein dependent on myosin-9 and its C-terminal fragment. MICAL2-ΔC-enriched in the nucleus-had less impact on tumor malignancy in LUAD cells in vitro and in vivo. Tumor promotion by MICAL2 was reduced by nuclear-export inhibitor, myosin-9 inhibitor, or si-myosin-9-all of which effectively inhibited MICAL2's nuclear export. Finally, the expression and subcellular location as well as clinical significance of MICAL2 and myosin-9 were analyzed across TCGA data and LUAD tissue arrays. Our data revealed that MICAL2 overexpression and nuclear export were associated with cancer progression; inhibiting its expression and/or nuclear export may provide a new target for LUAD therapy.

Solitary Metastasis in the Mediastinal Lymph Node After Radical Nephrectomy for Clear Cell Renal Cell Carcinoma: A Case Report and Literature Review.

BACKGROUND: Renal cell carcinoma can metastasize to virtually any anatomical site throughout the body, especially the lung, bone, lymph nodes, liver, and brain. However, it is extremely rare for renal cell carcinoma to metastasize solely to the mediastinal lymph node more than 15 years after radical nephrectomy. CASE PRESENTATION: The case we present here is that of a 50-year-old Chinese male with an isolated posterior mediastinal lymph node metastasis of clear cell renal cell carcinoma 16 years after radical nephrectomy. However, based on imaging examination, the mass was clinically misdiagnosed as Castleman's disease before operation. Following surgical excision of the mass, it was finally judged to be a metastasis from clear cell renal cell carcinoma according to the patient's medical history and immunohistochemical findings. Currently, there is no clinical or radiological finding the recurrence of metastasis after 10 months of follow-up. CONCLUSION: We report a case of solitary metastasis in the posterior mediastinal lymph node 16 years after radical nephrectomy for clear cell renal cell carcinoma. Given the long disease-free interval between primary renal cell carcinoma to isolated mediastinal lymph node metastasis, it is important to conduct a lifelong regular follow-up, including thoracic computed tomography. In addition, surgical resection remains the best method of treatment for mediastinal lymph node metastases from clear cell renal cell carcinoma if the metastatic lesion is limited.

New perspective on SH2B1: An accelerator of cancer progression.

SH2B1 is well-known as an adaptor protein, and deletion of SH2B1 results in severe obesity and both leptin and insulin resistance. Some studies have revealed that SH2B1 is involved in the progression of lung cancer, esophageal cancer, gastric cancer, oropharyngeal cancer, and so on. Biological function experiments have proven that SH2B1 can regulate cellular morphology, motility and adhesion by modifying the actin cytoskeletal reorganization, and it can promote cell mitogenesis, transformation, survival and differentiation via different signal pathways by enhancing the kinase activity of several receptor tyrosine kinases. In addition, SH2B1 is an obesity-related gene, and epidemiological surveys suggest a complex relationship between obesity and cancer. Therefore, what is the relationship between SH2B1 and cancer? Herein, we attempt to provide a mini overview of the roles of SH2B1 in cancer.

Recent Progress in Characterizing Long Noncoding RNAs in Cancer Drug Resistance.

Drug resistance is an important cause of failure in cancer chemotherapies. A large number of long noncoding RNAs (lncRNAs) have been found to be related to drug resistance in cancers. Therefore, lncRNAs provide potential targets for cancer therapies. The lncRNAs involved in cancer drug resistance are attracting interest from an increasing number of researchers. This review summarizes the latest research on the mechanisms and functions of lncRNAs in cancer drug resistance and envisages their future developments and therapeutic applications. This research suggests that lncRNAs regulate drug resistance through multiple mechanisms. LncRNAs do not affect drug resistance directly; usually, they do so by regulating the expression of some intermediate regulatory factors. In addition, lncRNAs exhibit a diversity of functions in cancer drug resistance. The overexpression of most lncRNAs promotes drug resistance, while a few lncRNAs have inhibitory effects.

[Research Progress of Pulmonary Epithelioid Hemangioendothelioma].

Epithelioid hemangioendothelioma (EHE) is a rare vascular neoplasm that develops from vascular endothelial cells. It has been reported to occur many sites of body, but the most common EHE presentations are soft tissue (limbs), bone, liver and lung. Compared with other pulmonary tumors, pulmonary epithelioid hemangioendothelioma (P-EHE) is relatively rare. According to a literature review, more than 100 cases have been described all over the world. Due to the low incidence of P-EHE, lack of specificity in clinical symptoms and radiological findings, it is often misdiagnosed. Meanwhile, many patients do not receive appropriate treatment, resulting in poor prognosis in some cases. Histology and immunohistochemical methods are essential for diagnosis. However, there is no established standard treatment for P-EHE, because of the rarity of the disease. When the lesions are small and limited in number, surgical is the best treatment, achieving the purpose of diagnosis and treatment at the same time. This article tries to present the etiopathogenesis, clinical manifestations, diagnosis, treatment and prognosis of P-EHE.
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LINC81507 act as a competing endogenous RNA of miR-199b-5p to facilitate NSCLC proliferation and metastasis via regulating the CAV1/STAT3 pathway.

Lung cancer is the leading cause of cancer-related mortality worldwide. Recently, accumulating data indicate that long noncoding RNAs (LncRNAs) function as novel crucial regulators of diverse biological processes, including proliferation and metastasis, in tumorigenesis. Lnc NONHSAT081507.1 (LINC81507) is associated with lung adenocarcinoma. However, its pathological role in non-small cell lung cancer (NSCLC) remains unknown. In our study we investigated the role of LINC81507 in NSCLC. The expression of LINC81507 was analyzed in 105 paired NSCLC tumor specimens and paired adjacent non-tumorous tissues from NSCLC patients by real-time quantitative PCR (RT-qPCR). Gain- and loss-of-function experiments were conducted to investigate the functions of LINC81507, miR-199b-5p and CAV1. Reduced expression of LINC81507 resulted in cell growth, proliferation, migration and epithelial-mesenchymal transition (EMT) in NSCLC cells, whereas ectopic overexpression of LINC81507 resulted in the opposite effects both in vitro and in vivo. Nuclear and Cytoplasmic fractionation assays showed LINC81507 mainly resided in cytoplasm. Bioinformatics analysis and dual-luciferase assays revealed that miR-199b-5p was a direct target of LINC81507 through binding Ago2. Mechanistic analysis demonstrated that miR-199b-5p specifically targeted the Caveolin1 (CAV1) gene, and LINC81507 inactivated the STAT3 pathway in a CAV1-dependent manner. Taken together, LINC81507 is decreased in NSCLC and functions as a sponge to miR-199b-5p to regulate CAV1/STAT3 pathway, which suggests that LINC81507 serve as a tumor suppressor and potential therapeutic target and biomarker for metastasis and prognosis in NSCLC.

Risk factors associated with prolonged air leak after video-assisted thoracic surgery pulmonary resection: a predictive model and meta-analysis.

BACKGROUND: This study aimed to establish a predictive model for prolonged air leak (PAL) after video-assisted thoracic surgery (VATS) lung resection; and additionally, to present a meta-analysis of the relevant literature to estimate the association between various clinical factors and PAL. METHODS: A retrospective, case-control study was conducted using univariate analysis and logistic regression based on 493 medical records from patients who underwent VATS lung resection between January 2015 and August 2017 at our institution. PAL was defined as air leak more than 5 days after lung surgery. Subsequently, a nomogram was established as a predictive model. Relevant studies were screened from PubMed, Embase and Cochrane for relevant studies and data was extracted from those enrolled. Pooled odds ratios or weighted mean differences with corresponding 95% confidence intervals were calculated to estimate the association between various clinical factors and PAL. RESULTS: Incidence of PAL after VATS lung resection was observed in 54 (10.8%) of 493 patients. Logistic regression revealed that smoking (P=0.014), pulmonary function (P=0.011), pleural adhesion (P<0.001), stapling length (P<0.001), early postoperative drainage (P=0.002) were significantly associated with PAL. Our meta-analysis, including 17 eligible studies and 14 potential risk factors, further validating our findings. Upper lobectomy was determined to be a significant risk factor for PAL in Europeans and North Americans (OR =2.03, P<0.001), but not in Asians (OR =1.04, P=0.610). Importantly, the constructed nomogram demonstrated a good predictive ability (C-index =0.858). CONCLUSIONS: Lung stapling length and early postoperative drainage are important indicators for the evaluation of PAL occurrence. Upper pulmonary resection is a factor with particular regional differences as its association with PAL is not significant within Asian populations. Our nomogram, incorporating multiple factors, provided a simple and practical predictive model with value for clinical application.

The long noncoding RNA LINC00312 induces lung adenocarcinoma migration and vasculogenic mimicry through directly binding YBX1.

Vasculogenic mimicry (VM) gives rise to tumor neovascularization that is critical for tumor growth and metastasis. Long non-coding RNAs (lncRNAs) have been implicated in diverse and fundamental biological processes. LINC00312 is associated with lung adenocarcinoma. In this study, we found that LINC00312 induced migration, invasion and VM of lung cancer cells by direct binding to the transcription factor Y-Box Binding Protein 1 (YBX1). Moreover, we demonstrated that YBX1 is associated with different fragments within 0-2410 nt 5'region of LINC00312. In addition, LINC00312 is associated with VM in 124 lung adenocarcinoma clinical specimens. The results suggest that LINC00312 is a promising therapeutic and diagnostic target for lung adenocarcinoma.