Vaporization of perfluorocarbon attenuates sea-water-drowning-induced acute lung injury by deactivating the NLRP3 inflammasomes in canines.

Seawater-drowning-induced acute lung injury (SD-ALI) is a life-threatening disorder characterized by increased alveolar-capillary permeability, an excessive inflammatory response, and refractory hypoxemia. Perfluorocarbons (PFCs) are biocompatible compounds that are chemically and biologically inert and lack toxicity as oxygen carriers, which could reduce lung injury in vitro and in vivo. The aim of our study was to explore whether the vaporization of PFCs could reduce the severity of SD-ALI in canines and investigate the underlying mechanisms. Eighteen beagle dogs were randomly divided into three groups: the seawater drowning (SW), perfluorocarbon (PFC), and control groups. The dogs in the SW group were intratracheally administered seawater to establish the animal model. The dogs in the PFC group were treated with vaporized PFCs. Probe-based confocal laser endomicroscopy (pCLE) was performed at 3 h. The blood gas, volume air index (VAI), pathological changes, and wet-to-dry (W/D) lung tissue ratios were assessed. The expression of heme oxygenase-1 (HO-1), nuclear respiratory factor-1 (NRF1), and NOD-like receptor family pyrin domain containing-3 (NLRP3) inflammasomes was determined by means of quantitative real-time polymerase chain reaction (qRT-PCR) and immunological histological chemistry. The SW group showed higher lung injury scores and W/D ratios, and lower VAI compared to the control group, and treatment with PFCs could reverse the change of lung injury score, W/D ratio and VAI. PFCs deactivated NLRP3 inflammasomes and reduced the release of caspase-1, interleukin-1ß (IL-1ß), and interleukin-18 (IL-18) by enhancing the expression of HO-1 and NRF1. Our results suggest that the vaporization of PFCs could attenuate SD-ALI by deactivating NLRP3 inflammasomes via the HO-1/NRF1 pathway.

Computed tomography-based radiomics improves non-invasive diagnosis of Pneumocystis jirovecii pneumonia in non-HIV patients: a retrospective study.

BACKGROUND: Pneumocystis jirovecii pneumonia (PCP) could be fatal to patients without human immunodeficiency virus (HIV) infection. Current diagnostic methods are either invasive or inaccurate. We aimed to establish an accurate and non-invasive radiomics-based way to identify the risk of PCP infection in non-HIV patients with computed tomography (CT) manifestation of pneumonia. METHODS: This is a retrospective study including non-HIV patients hospitalized for suspected PCP from January 2010 to December 2022 in one hospital. The patients were randomized in a 7:3 ratio into training and validation cohorts. Computed tomography (CT)-based radiomics features were extracted automatically and used to construct a radiomics model. A diagnostic model with traditional clinical and CT features was also built. The area under the curve (AUC) were calculated and used to evaluate the diagnostic performance of the models. The combination of the radiomics features and serum ß-D-glucan levels was also evaluated for PCP diagnosis. RESULTS: A total of 140 patients (PCP: N = 61, non-PCP: N = 79) were randomized into training (N = 97) and validation (N = 43) cohorts. The radiomics model consisting of nine radiomic features performed significantly better (AUC = 0.954; 95% CI: 0.898-1.000) than the traditional model consisting of serum ß-D-glucan levels (AUC = 0.752; 95% CI: 0.597-0.908) in identifying PCP (P = 0.002). The combination of radiomics features and serum ß-D-glucan levels showed an accuracy of 95.8% for identifying PCP infection (positive predictive value: 95.7%, negative predictive value: 95.8%). CONCLUSIONS: Radiomics showed good diagnostic performance in differentiating PCP from other types of pneumonia in non-HIV patients. A combined diagnostic method including radiomics and serum ß-D-glucan has the potential to provide an accurate and non-invasive way to identify the risk of PCP infection in non-HIV patients with CT manifestation of pneumonia. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05701631).

Probe-based confocal laser endomicroscopy for evaluating high-altitude pulmonary edema in canines.

Background: Real-time assessment of high-altitude pulmonary edema (HAPE) remains a challenge. Probe-based confocal laser microscopy (pCLE) allows a real-time in vivo visualization of the alveoli. This study aimed to develop a new non-invasive method for analyzing microscopic images in a canine model of HAPE using pCLE. Materials and methods: This was a prospective, controlled animal study in adult male beagle dogs randomized to control and HAPE groups. The HAPE group was exposed to a high altitude of 6000 m for 48 h. The blood gas levels, lung morphological changes, infectious factors, and lung wet-to-dry ratio were analyzed in different groups. The pCLE images were described based on the volume air index (VAI), which applies an integral over specific signal intensities. Results: The lung wet-to-dry weight ratio and injury scores in the HAPE group were significantly increased compared with those of the control group. The levels of infectious factors interleukin-1 beta, tumor necrosis factor-alpha, and interleukin-6 were significantly increased in the HAPE group compared with those in the control group. VAI was significantly decreased in the HAPE group. Conclusion: pCLE is a potential adjudicative bronchoscopic imaging technique for assessing HAPE. VAI may be acquired from quantitative parameters in the analysis of images.

Regiodivergent and Stereoselective Synthesis of Highly Substituted 1,3-Dienes via Arylative Acyloxy Migration of Propargyl Esters.

We report the first catalyst-controlled regiodivergent method that enables the synthesis of structurally diverse 1,2,3,4-tetrasubstituted conjugated dienes with excellent regio- and stereochemical outcomes from the same set of readily available propargyl esters and diaryliodonium salts. In this diene chemistry, the in situ generated, highly electrophilic aryl-CuIII complex serves not only as a π-Lewis acid catalyst for alkyne activation/acyloxy migration but also as an aryl electrophile equivalent. The competitive arylative 1,2- and 1,3-acyloxy migration patterns are exquisitely dictated by Cu and Au/Cu relay catalyses, respectively, providing a modular and attractive approach to traditionally inaccessible tetrasubstituted 1,3-dienes in a regiodivergent manner. Finally, the synthetic utility of this method is demonstrated by further synthetic derivatization of 1,3-dienes into an array of useful compounds.

Manganese-Catalyzed Redox-Neutral Thiolation of Alkyl Halides with Thioformates.

Transition metal-catalyzed C-S cross-coupling has emerged as an important strategy to furnish thioethers; however, the dominant utilization of noble metal catalysts as well as the construction of challenging C(sp3 )-S bonds by transition metal-catalysis remain highly problematic. Earth-abundant manganese has gathered increasing interest as an attractive catalyst for new reaction development; nevertheless, C(sp3 )-S cross-coupling reaction by manganese catalysis has not been reported. Herein, we disclose a highly efficient manganese-catalyzed redox-neutral thiolation of a broad range of alkyl halides with thioformates as practical sulfuration agents. Strategically, employing easily synthesized thioformates as thiyl radical precursors allows access to various aryl and alkyl thioethers in good to excellent yields. Notably, this redox-neutral method avoids the utilization of strong bases, external ligands, forcing reaction conditions, and stoichiometric manganese, thus presenting apparent advantages, such as broad substrate scope, excellent functional group compatibility, and mild reaction conditions. Finally, the utilities of this method are also illustrated by downstream transformations and late-stage thiolation of structurally complex natural products and pharmaceuticals.

Establishing a predictive model for tumor mutation burden status based on CT radiomics and clinical features of non-small cell lung cancer patients.

Background: Tumor mutation burden (TMB) is one of the biomarkers for efficacy of immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC). Due to the potential of radiomic signatures to identify microscopic genetic and molecular differences, thus radiomics is considered a suitable tool for judging the TMB status probably. In this paper, the radiomics method was applied to analyze the TMB status of NSCLC patients, so as to construct a prediction model for distinguishing between TMB-high and TMB-low status. Methods: A total of 189 NSCLC patients with TMB detection result were retrospectively included between 30 November 2016 and 1 January 2021, and were divided into two groups: TMB-high (≥10/Mb, 46 patients) and TMB-low (<10/Mb, 143 patients). Some clinical features related to TMB status were screened out in 14 clinical features and 2,446 radiomic features were extracted. All patients were randomly divided into a training set (n=132) and a validation set (n=57). Univariate analysis and least absolute shrinkage and selection operator (LASSO) were used for radiomics feature screening. A clinical model, radiomics model, and nomogram were constructed with the above screened features and compared. Decision curve analysis (DCA) was used to evaluate the clinical value of the established models. Results: Two clinical features (smoking history, pathological type) and 10 radiomics features were significantly correlated with the TMB status. The prediction efficiency of the intra-tumoral model was better than that of the peritumoral model (AUC: 0.819 vs. 0.816; accuracy: 0.773 vs. 0.632, specificity: 0.767 vs. 0.558). The efficacy of the prediction model based on radiomic features was significantly better than that of the clinical model (AUC: 0.822 vs. 0.683; specificity: 0.786 vs. 0.643). The nomogram, established by combining smoking history, pathologic type, and rad-score, showed the best diagnostic efficacy (AUC =0.844) and had potential clinical value in assessing the TMB status of NSCLC. Conclusions: The radiomics model based on CT images of NSCLC patients performed well in distinguishing the status of TMB-high and TMB-low, and the nomogram could provide additional information on the timing and regimen of immunotherapy.

Directed Asymmetric Nickel-Catalyzed Reductive 1,2-Diarylation of Electronically Unactivated Alkenes.

Transition-metal catalyzed intermolecular 1,2-diarylation of electronically unactivated alkenes has emerged as an extensive research topic in organic synthesis. However, most examples are mainly limited to terminal alkenes. Furthermore, transition-metal catalyzed asymmetric 1,2-diarylation of unactivated alkenes still remains unsolved and is a formidable challenge. Herein, we describe a highly efficient directed nickel-catalyzed reductive 1,2-diarylation of unactivated internal alkenes with high diastereoselectivities. More importantly, our further effort towards enantioselective 1,2-diarylation of the unactivated terminal and challenging internal alkenes is achieved, furnishing various polyarylalkanes featuring benzylic stereocenters in high yields and with good to high enantioselectivities and high diastereoselectivities. Interestingly, the generation of cationic Ni-catalyst by adding alkali metal fluoride is the key to increased efficiency of this enantioselective reaction.

Endobronchial valve therapy for patients with advanced emphysema. A report from a tertiary care center in China.

OBJECTIVES: To assess the efficiency and safety of endobronchial valve (EBV) treatment in Chinese patients. METHODS: A retrospective analysis was performed in patients with chronic obstructive pulmonary disease who underwent EBV implantation in our hospital between October 2010 and January 2017. All patients were confirmed with no collateral ventilation (CV-) or with low airflow (LF) in the treated lobe. Pulmonary function parameters, the 6-minute walk distance (6MWD), the modified Medical Research Council (mMRC), as well as adverse events in the follow-up period were recorded. RESULTS: Thirty-eight advanced emphysema patients received EBV implantation. Significant improvements were found in forced expiratory volume in 1 second (FEV1)(FEV1: +0.12 L), 6MWD (+64.9 m), and mMRC (-0.5 points). A total of 55.3% and 65.8% of subjects met the score for the minimal clinically important difference in FEV1 and 6MWD, respectively. FEV1 improved more significantly in the CV- group than in the LF group. Pneumothorax or death did not occur during the follow-up period. CONCLUSION: Endobronchial valve treatment in patients with advanced emphysema and CV- provides clinically meaningful benefits with a low incidence of pneumothorax. The efficiency and safety of EBV therapy are acceptable in China.

Nickel-Catalyzed Enantioselective Coupling of Acid Chlorides with α-Bromobenzoates: An Asymmetric Acyloin Synthesis.

The reaction of common acyl-metal species (acyl anion) with aldehydes to furnish acyloins has received much less attention and specifically was restricted to using preformed stoichiometric acyl-metal reagents. Moreover, the (catalytic) enantioselective variants remain unexplored, and the asymmetric synthesis of chiral acyloins has met significant challenges in organic synthesis. Here, we uncover the highly enantioselective coupling of acid chlorides with α-bromobenzoates by nickel catalysis for producing enantioenriched protected α-hydroxy ketones (acyloins, >60 examples) with high enantioselectivities (up to 99% ee). The successful execution of this enantioselective coupling protocol enables the formation of a key ketyl radical from α-bromoalkyl benzoate in situ generated from corresponding aldehyde and acyl bromide, which finally is captured by chiral acyl-Ni species catalytically in situ formed from acyl chlorides, thus avoiding the use of preformed acyl-metal reagents. The synthetic utility of this chemistry is demonstrated in the downstream synthetic elaboration toward a diverse set of synthetically valuable chiral building blocks and biologically active compounds.

Correlation between PD-L1 expression and radiomic features in early-stage lung adenocarcinomas manifesting as ground-glass nodules.

Background: Immunotherapy might be a promising auxiliary or alternative systemic treatment for early-stage lung adenocarcinomas manifesting as ground-glass nodules (GGNs). This study intended to investigate the PD-L1 expression in these patients, and to explore the non-invasive prediction model of PD-L1 expression based on radiomics. Methods: We retrospectively analyzed the PD-L1 expression of patients with postoperative pathological diagnosis of lung adenocarcinomas and with imaging manifestation of GGNs, and divided patients into positive group and negative group according to whether PD-L1 expression ≥1%. Then, CT-based radiomic features were extracted semi-automatically, and feature dimensions were reduced by univariate analysis and LASSO in the randomly selected training cohort (70%). Finally, we used logistic regression algorithm to establish the radiomic models and the clinical-radiomic combined models for PD-L1 expression prediction, and evaluated the prediction efficiency of the models with the receiver operating characteristic (ROC) curves. Results: A total of 839 "GGN-like lung adenocarcinoma" patients were included, of which 226 (26.9%) showed positive PD-L1 expression. 779 radiomic features were extracted, and 9 of them were found to be highly corelated with PD-L1 expression. The area under the curve (AUC) values of the radiomic models were 0.653 and 0.583 in the training cohort and test cohort respectively. After adding clinically significant and statistically significant clinical features, the efficacy of the combined model was slightly improved, and the AUC values were 0.693 and 0.598 respectively. Conclusions: GGN-like lung adenocarcinoma had a fairly high positive PD-L1 expression rate. Radiomics was a hopeful noninvasive method for predicting PD-L1 expression, with better predictive efficacy in combination with clinical features.

Development of a diagnostic model for malignant solitary pulmonary nodules based on radiomics features.

Background: This study proposed a precise diagnostic model for malignant solitary pulmonary nodules (SPNs). This model can be used to identify objective and quantifiable image features and guide the clinical treatment strategy adopted for SPNs. This model will help clinicians optimize management strategies for SPN. Methods: In this retrospective study, the clinical data of 455 patients of SPN with defined pathological diagnosis between September 2016 and August 2019 were collected and analyzed. The data included pathological diagnosis, preoperative computed tomography (CT) diagnosis, gender, age, smoking history, family history of tumor, previous history, and contact history data. The quantitative image features and radiomic information of the SPNs were provided using computer-aided detection (CAD) "digital lung" software. The Chi-squared test was used to assess the accuracy between CAD and conventional CT in the diagnosis of SPNs. The diagnostic model for benign or malignant SPNs was developed using a multivariate logistic regression analysis that comprises 6 radiomic factors (irregularity, average diameter, COPD910, proportion of emphysema, proportion of fat, and average density of related blood vessels). The area under the receiver operating characteristic curve was used to evaluate the performance of the model in determining SPN risk of malignancy. Results: There was a statistical difference in the accuracy of CAD and conventional CT in diagnosing SPNs. According to the golden standard pathological diagnosis, the diagnostic accuracy of CAD (81%) was higher than that of conventional CT (63.7%) (P<0.05). Six variables (i.e., irregularity, the mean diameter, COPD910, the proportion of emphysema, the proportion of fat, and the vascular density) were identified using multivariable logistic regression to establish the diagnostic model for distinguish benign or malignant SPNs. The area under the receiver operating characteristic (ROC) curve (AUC) of the diagnostic model was 0.876 (95% CI: 0.8445-0.9076), and its sensitivity and specificity were 81.25% and 82.56% respectively. Conclusions: The proposed diagnostic model, which comprises 6 radiomic factors, is accurate and effective at diagnosing benign or malignant SPNs.

Palladium-Catalyzed Regiodivergent Synthesis of 1,3-Dienyl and Allyl Esters from Propargyl Esters.

Catalyst-controlled regiodivergent catalysis is a vital chemical tool that allows efficient access to large collections of structurally diverse molecules from a common precursor but remains a challenge. We report a catalyst-controlled, tunable, and predictable regiodivergency in transforming the internal aliphatic propargyl esters into diverse libraries of highly substituted 1,3-dienyl and allyl products by Pd-catalysis. Depending on the ligand employed, the palladium catalyst can involve two typical approaches: electrophilic palladium catalysis and a sequential oxidative addition-reductive elimination pathway. This regiodivergent protocol endows facile access to four regioisomers with high regio- and stereoselectivity from the common propargyl esters. In terms of synthetic utility, a notable feature of this protocol is amenable to structural diversification of bioactive relevant molecules, enabling rapid assembly of many useful structural analogs of pharmaceutical candidates.

[Clinical Recommendations for Perioperative Immunotherapy-induced Adverse Events in Patients with Non-small Cell Lung Cancer].

BACKGROUND: Perioperative treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancelation of surgery, additional illness, and even death, and have therefore attracted much attention. The purpose of the clinical recommendations is to form a diagnosis and treatment plan suitable for the current domestic medical situation for the immune-related adverse event (irAE). METHODS: This recommendation is composed of experts in thoracic surgery, oncologists, thoracic medicine and irAE related departments (gastroenterology, respirology, cardiology, infectious medicine, hematology, endocrinology, rheumatology, neurology, dermatology, emergency section) to jointly complete the formulation. Experts make full reference to the irAE guidelines, large-scale clinical research data published by thoracic surgery, and the clinical experience of domestic doctors and publicly published cases, and repeated discussions in multiple disciplines to form this recommendation for perioperative irAE. RESULTS: This clinical recommendation covers the whole process of prevention, evaluation, examination, treatment and monitoring related to irAE, so as to guide the clinical work comprehensively and effectively. CONCLUSIONS: Perioperative irAE management is an important part of immune perioperative treatment of lung cancer. With the continuous development of immune perioperative treatment, more research is needed in the future to optimize the diagnosis and treatment of perioperative irAE.

Novel Resistance Mechanisms to Osimertinib Analysed by Whole-Exome Sequencing in Non-Small Cell Lung Cancer.

PURPOSE: Molecular-based targeted therapy has improved life expectancy for advanced non-small cell lung cancer (NSCLC). However, it does not have to be inevitable that patients receiving third-generation EGFR-TKIs become drug resistant. EGFR C797S and MET amplification are common mechanisms of osimertinib. However, a large part of these potential drug mechanisms remains unknown, and further research is needed. METHODS: Tumour and blood samples from forty advanced NSCLC patients were identified as acquired drug resistant to osimertinib. The NGS panel was applied to detect EGFR C797S and MET amplification in tumour tissues or plasma samples. Whole-exome sequencing was conducted in five pairs of tumour tissues obtained before osimertinib administration and after osimertinib resistance in patients without C797S/cMET amplification. RESULTS: The overall C797S mutation rate was 20%, and MET amplification was detected in six out of sixteen C797S-negative samples. PDGFRA in the PI3K-AKT-mTOR signalling pathway, RASAL2, RIN3 and SOS2 in the RAS-Raf-ERK signalling pathway, PTK2 in the ERBB signalling pathway and ABCC1 and ABCB5 in the ABC membrane pump system were identified as candidate crucial genes of drug resistance to osimertinib. CONCLUSION: EGFR C797S mutation and MET amplification are leading mechanisms for osimertinib resistance in lung cancer. The crucial potential mutated genes defined in our present study may need further validation in a considerable number of lung cancer patients.

Clinical recommendations for perioperative immunotherapy-induced adverse events in patients with non-small cell lung cancer.

Perioperative adjuvant treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). In particular, the success of immune checkpoint inhibitors, such as antibodies against PD-1 and PD-L1, in patients with lung cancer has increased our expectations for the success of these therapeutics as neoadjuvant immunotherapy. Neoadjuvant therapy is widely used in patients with resectable stage IIIA NSCLC and can reduce primary tumor and lymph node stage, improve the complete resection rate, and eliminate microsatellite foci; however, complete pathological response is rare. Moreover, because the clinical benefit of neoadjuvant therapy is not obvious and may complicate surgery, it has not yet entered the mainstream of clinical treatment. Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancellation of surgery, additional illness, and even death, and have therefore attracted much attention. In this article, we draw on several sources of information, including (i) guidelines on adverse reactions related to immune checkpoint inhibitors, (ii) published data from large-scale clinical studies in thoracic surgery, and (iii) practical experience and published cases, to provide clinical recommendations on adverse events in NSCLC patients induced by perioperative immunotherapy.

The management of elderly patients with lung cancer: a single center retrospective study.

BACKGROUND: The incidence of lung cancer in patients aged over 80 years accounts for 30% of the entire lung cancer population. However, the emphasis on the treatment and prognosis of this subpopulation remains poorly investigated. This study evaluated outcomes associated with treatment strategies for these patients. METHODS: A retrospective analysis was performed on the overall survival and treatment of deceased patients over 80 years of age, diagnosed with lung cancer in our hospital. Treatment and overall survival were evaluated using logistic regression, the Kaplan-Meier method, and multivariable Cox proportional hazard models. RESULTS: A total of 56 patients were included in this study, with 30 (53.6%) patients diagnosed with stage IV at the time of detection. One-third of the patients refused any form of treatment. The majority (n=27, 48.2%) of the included patients with stage I-IV lung cancer received chemotherapy or tyrosine kinase inhibitors (TKIs). The median overall survival was determined to be 9.067±1.2477 months, with the median survival time of small cell lung cancer (SCLC) patients calculated as 7.167±3.797 months for the entire cohort. The majority of patients exhibited lesions in the left upper lung and displayed the longest overall survival. For the over 80 yrs with lunch cancer patients, that who chose not to receive any treatment exhibited a shorter overall survival than those who received treatment. CONCLUSIONS: Most patients in this study presented with advanced disease. Treatment-naïve patients exhibited a poorer prognosis compared to their counterparts who received treatment, highlighting the need for this subpopulation to access further treatment.

A case-control study of human immunodeficiency virus-negative patients with cryptococcemia and cryptococcal meningitis in a Chinese tertiary care hospital during 10 years.

OBJECTIVE: This study aimed to characterize patients with cryptococcemia and compare the clinical features of cryptococcemia and cryptococcal meningitis. METHODS: This was a retrospective, case-control study. We retrospectively identified blood cultures with Cryptococcus spp. growth. Controls were hospitalized patients who suffered from cryptococcal meningitis, but did not experience cryptococcemia. Controls and cases were matched by admission date, age, sex, and body weight. Clinical information was analyzed by two independent reviewers. RESULTS: Eight patients with cryptococcemia and eight patients with cryptococcal meningitis were included. They were all negative for human immunodeficiency virus. The most common underlying disease was primary nephrotic syndrome. All patients presented with fever. The incidence of headache, nausea/vomiting, seizures, and cough/expectoration was significantly lower in patients with cryptococcemia than in those with cryptococcal meningitis. All clinical strains of Cryptococcus, except for one, were sensitive to fluconazole, voriconazole, itraconazole, amphotericin B, and flucytosine in vitro. The rate of receiving an amphotericin B-containing regimen was significantly higher in patients with cryptococcal meningitis than in those with cryptococcemia. In-hospital mortality was significantly higher in cryptococcemia cases compared with cryptococcal meningitis cases. CONCLUSION: Cryptococcemia is an unusual infection characterized by a high mortality. Cryptococcemia requires early identification and prompt antifungal therapy.

POLE2 Serves as a Prognostic Biomarker and Is Associated with Immune Infiltration in Squamous Cell Lung Cancer.

BACKGROUND Squamous cell lung cancer is the main cause of cancer-associated mortality. The discovery of promising prognostic biomarkers for predicting the survival of patients with squamous cell lung cancer remains a challenge. MATERIAL AND METHODS Gene expression profiles of GSE33479 and GSE51855, including 42 squamous cell lung cancer tissues and 17 normal tissues, from the GEO database were assessed to find common differentially expressed genes (DEGs) via the GEO2R online tool and Venn diagram software. Then, gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analyses were conducted. The key protein-protein interaction (PPI) network within those common DEGs was subsequently illustrated through a combination of Search Tool for Retrieval of Interacting Genes (STRING) and Cytoscape software. Finally, core genes associated with survival and levels of immune infiltration were demonstrated by the Kaplan-Meier plotter and Tumor Immune Estimation Resource (TIMER) online database, respectively. RESULTS In total, 483 DEGs were involved, including 216 upregulated genes enriched in "cell division", "DNA replication", and "DNA repair pathway" and 267 downregulated genes enriched in "cell adhesion", "oxidation-reduction process", and "cell-cell signaling". The 75 core genes were selected by Molecular Complex Detection applied in Cytoscape. Four genes - MND1, FOXM1, CDC6, and POLE2 - were found to be significantly associated with survival. Further analysis of the KEEG pathway and TIMER database revealed that only POLE2 was enriched in "DNA replication" and its higher expression was negatively associated with survival and immune infiltration. CONCLUSIONS Higher expression of POLE2 is a prognosis-related biomarker for worse survival and is negatively associated with immune infiltration in squamous cell lung cancer.

MIR205HG facilitates carcinogenesis of lung squamous cell carcinoma in vitro revealed by long noncoding RNA profiling.

As a subtype of non-small-cell lung cancer, lung squamous cell carcinoma (LUSC) accounts for one-fifth of all lung cancers. Unfortunately, no specific targetable aberration has yet been identified. Hence, it is of huge urgency and potential to identify aberrantly regulated genes in LUSC. Here, five pairs of LUSC samples and their corresponding adjacent tissues were subject to whole transcriptome sequencing. Our results showed that CTD-2562J17.6 and FENDRR were significantly downregulated while MIR205HG, LNC_000378, RP11-116G8.5, RP3-523K23.2, and RP5-968D22.1 were significantly upregulated in all five LUSC samples. Importantly, MIR205HG was upregulated in LUSC clinical samples as well as in LUSC cell lines. Interestingly, our results demonstrated that the expression level of MIR205HG is positively correlated with the malignancy. In addition, MIR205HG is required for LUSC cell growth and cell migration. Most importantly, our results showed that MIR205HG prohibits LUSC apoptosis via regulating Bcl-2 and Bax. Taken together, our data shed lights on the lncRNA regulatory nexus that controls the carcinogenesis of LUSC and provided potential novel diagnostic markers and therapeutic targets for LUSC.