Global burden of esophageal cancer attributable to high BMI in 204 countries and territories: 1990-2019.

BACKGROUND: Esophageal cancer (EC), a common and fatal disease, includes two histological subtypes; esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (ECA). To aid policymakers in the allocation of resources for the prevention and treatment of EC, updated data on EC deaths and disability-adjusted life years (DALYs) attributable to high body mass index (BMI) are necessary. The objective of this study was to identify trends in EC associated with high BMI between 1990 and 2019 using 2019 Global Burden of Disease data. METHODS: In this observational population-based study, epidemiological data on the association between high BMI and EC were obtained from GBD 2019. The age-standardized mortality rate (ASMRs) and disability-adjusted life year rate (ASDRs) attributable to high BMI-related EC were stratified by year, age, country, and sociodemographic index (SDI). The estimated annual percentage change (EAPC) was calculated to evaluate the temporal trends of the ASMRs and ASDRs between 1990 and 2019. RESULTS: In 2019, the proportion of EC deaths and DALYs attributed to high BMI was 18.1% and 18.9%, respectively, resulting in 89 904 (95% confidence interval [CI]: 27 879-171 255) deaths and 2 202 314 (95% CI: 681 901-4 173 080) DALYs. High BMI-related deaths and DALYs showed a strong upward trend, increasing by more than two-fold since 1990. East Asia and Western Europe showed the highest risk of EC mortality and DALYs attributable to high BMI; China and the USA bear the greatest burden. The ASMR and ASDR increased in five SDI regions. CONCLUSIONS: The incidence of EC is increasing, particularly in developing nations, which may be attributed to the prevalence of high BMI. To mitigate the impact of high BMI on the incidence of EC, it is important to increase awareness of its deleterious effects, which may alleviate the burden of this disease.

Plasma cell-free DNA 5-hydroxymethylcytosine and whole-genome sequencing signatures for early detection of esophageal cancer.

Esophageal cancer is a highly incidence and deadly disease with a poor prognosis, especially in developing countries. Owing to the lack of specific symptoms and early diagnostic biomarkers, most patients are diagnosed with advanced disease, leading to a 5-year survival rate of less than 15%. Early (n = 50) and middle-advanced (n = 50) esophageal squamous cell carcinoma (ESCC) patients, as well as 71 healthy individuals, underwent 5-hydroxymethylcytosine (5hmC) sequencing on their plasma cell-free DNA (cfDNA). A Northern Chinese cohort of cfDNA 5hmC dataset of 150 ESCC patients and 183 healthy individuals were downloaded for validation. A diagnostic model was developed using cfDNA 5hmC signatures and then improved by low-pass whole genome sequencing (WGS) features of cfDNA. Conserved cfDNA 5hmC modification motifs were observed in the two independent ESCC cohorts. The diagnostic model with 5hmC features achieved an AUC of 0.810 and 0.862 in the Southern and Northern cohorts, respectively, with sensitivities of 69.3-74.3% and specificities of 82.4-90.7%. The performance was well maintained in Stage I to Stage IV, with accuracy of 70-100%, but low in Stage 0, 33.3%. Low-pass WGS of cfDNA improved the AUC to 0.934 with a sensitivity of 82.4%, a specificity of 88.2%, and an accuracy of 84.3%, particularly significantly in Stage 0, with an accuracy up to 80%. 5hmC and WGS could efficiently differentiate very early ESCC from healthy individuals. These findings imply a non-invasive and convenient method for ESCC detection when clinical treatments are available and may eventually prolong survival.

Inhibition of BPHL inhibits proliferation in lung carcinoma cell lines.

Background: Lung cancer is one of the most common human malignant tumors and the leading cause of cancer death worldwide. Biphenyl hydrolase-like (BPHL) is a gene encoding the human BPHL enzyme, a serine hydrolase that catalyzes the hydrolytic activation of amino acid ester prodrugs of nucleoside analogs such as valacyclovir and valganciclovir. However, the role of BPHL in lung cancer is still unknown. Methods: In this study, we assessed the effect BPHL knockdown on the proliferation, apoptosis, colony formation, metastasis, and cell cycle of cancer cells. BPHL knockdown NCI-H1299 and A549 cells demonstrated decreased proliferation, as measured by Celigo cell counting. The MTT assay results were consistent with Celigo cell counting. Caspase 3/7 activity increased significantly in the NCI-H1299 and A549 cells after shBPHL knockdown. Decreased colony formation in the NCI-H1299 and A54 cells after shBPHL knockdown, as measured by crystal violet staining. Transmigration assay using a Transwell demonstrated that there were significantly fewer migrating cells in the lower chamber in the BPHL knockdown NCI-H1299 and A549 cells. Cell cycle analysis by Propidium Iodide (PI) staining and fluorescence activated cell sorter (FACS). We also explored the effect of BPHL knockdown on tumor growth in a mouse model of tumor implantation in nude mice. Results: We found that the knockdown of BPHL gene expression by short hairpin RNA (shRNA) leads to a decrease in proliferation, colony formation, and metastasis and an increase in apoptosis in two lung adenocarcinoma (LUAD) cell lines in vitro. BPHL knockdown induces decreased tumor growth, colony formation, and metastasis; increased apoptosis; and altered cell cycle destruction. BPHL knockdown results in decreased tumor growth in vivo. Moreover, BPHL knockdown A549 cells demonstrated slower growth compared to control cells upon implantation in nude mice, confirming the in vitro findings. Conclusions: In this study, the data indicate that BPHL potentially promotes proliferation, inhibits apoptosis, and increases colony formation and metastasis in lung cancer. Overall, our study suggests that BPHL may be a gene that promotes tumor growth in lung cancer.

A deep learning based CT image analytics protocol to identify lung adenocarcinoma category and high-risk tumor area.

We present a protocol which implements deep learning-based identification of the lung adenocarcinoma category with high accuracy and generalizability, and labeling of the high-risk area on Computed Tomography (CT) images. The protocol details the execution of the python project based on the dataset used in the original publication or a custom dataset. Detailed steps include data standardization, data preprocessing, model implementation, results display through heatmaps, and statistical analysis process with Origin software or python codes. For complete details on the use and execution of this protocol, please refer to Chen et al. (2022).

Machine vision-assisted identification of the lung adenocarcinoma category and high-risk tumor area based on CT images.

Computed tomography (CT) is a widely used medical imaging technique. It is important to determine the relationship between CT images and pathological examination results of lung adenocarcinoma to better support its diagnosis. In this study, a bilateral-branch network with a knowledge distillation procedure (KDBBN) was developed for the auxiliary diagnosis of lung adenocarcinoma. KDBBN can automatically identify adenocarcinoma categories and detect the lesion area that most likely contributes to the identification of specific types of adenocarcinoma based on lung CT images. In addition, a knowledge distillation process was established for the proposed framework to ensure that the developed models can be applied to different datasets. The results of our comprehensive computational study confirmed that our method provides a reliable basis for adenocarcinoma diagnosis supplementary to the pathological examination. Meanwhile, the high-risk area labeled by KDBBN highly coincides with the related lesion area labeled by doctors in clinical diagnosis.

Olmesartan Attenuates Single-Lung Ventilation Induced Lung Injury via Regulating Pulmonary Microbiota.

Single-lung ventilation (SLV) associated acute lung injury is similar to ischemia reperfusion (IR) injury which is usually occurred during lung surgery. Olmesartan (Olm), a novel angiotensin receptor blocker (ARB), has been reported to ameliorate organ IR injury. Several recent studies have shown that lung microbiota may be involved in pulmonary diseases, but the effect of pulmonary microbiota in SLV-induced lung injury has not been reported. This study aims to determine the mechanism of how Olm attenuates SLV induced lung injury. Our data showed that 7 days Olm treatment before modeling markedly alleviated SLV-induced lung injury by suppressing inflammation and reactive oxygen species. Bronchoalveolar lavage fluid samples from the injured side were collected for 16S rRNA gene-based sequencing analysis and 53 different bacteria at the genus and species levels were identified. Furthermore, the injured lung samples were collected for metabolomics analysis using liquid chromatography-mass spectrometry analyses to explore differential metabolites. The Kyoto Encyclopedia of Genes and Genomes (KEGG) was applied to analyze the correlation between differential metabolites and lung microbiota. A total of 38 pathways were identified according to differential metabolites and 275 relevant pathways were enriched via analyzing the microbial community, 24 pathways were both identified by analyzing either metabolites or microbiota, including pyrimidine metabolism, purine metabolism, aminoacyl-tRNA biosynthesis and ATP-binding cassette transporter. Besides classical blockage of the renin-angiotensin II system, Olm could also alleviate SLV-induced lung injury by rewiring the interaction between pulmonary microbiota and metabolites.

Dielectric property measurements for the rapid differentiation of thoracic lymph nodes using XGBoost in patients with non-small cell lung cancer: a self-control clinical trial.

Background: One of the important criteria for thoracic surgeons in making surgical strategies is whether the thoracic lymph nodes (LNs) are metastatic. Frozen section (FS) is widely used as an intraoperative diagnostic method, which is time-consuming and expensive. The dielectric property, including permittivity and conductivity, varies with different tissues. The extreme gradient boosting (XGBoost) is a powerful classifier and widely used. Thus, this study aims to develop the rapid differentiation method combining dielectric property and XGBoost, and assess its efficacy on the thoracic LNs in patients with non-small cell lung cancer (NSCLC). Methods: This was a single center self-control clinical trial with paraffin pathology section (PPS) results as gold diagnosis. The LNs from the pathologically diagnosed patients with NSCLC were recruited, which were measured by open-ended coaxial probe for the dielectric property within 1-4,000 MHz after removal from the patients and then were sent to perform FS and PPS diagnosis. The XGBoost combining with dielectric property was developed to differentiate malignant LNs from benign LNs. The classified efficacy was determined using the receiver operator characteristic (ROC) curve and area under the curve (AUC). Results: A total of 204 LNs from 67 NSCLC patients were analyzed. The mean values of the two parameters differed significantly (P<0.001) between benign and malignant LNs. The AUC for permittivity and conductivity were 0.850 [95% confidence interval (CI): 0.786 to 0.915; P<0.001] and 0.887 (95% CI: 0.828 to 0.946; P<0.001), respectively. The AUC was 0.893 (95% CI: 0.834 to 0.951; P<0.001) when the two parameters were combined. After the application of the XGBoost, the AUC was 0.968 (95% CI: 0.918 to 1.000; P<0.001), and the accuracy was 87.80%. Its sensitivity was 58.33% and the specificity was 100%. When the Synthetic Minority Oversampling Technique (SMOTE) algorithm was used, the AUC was 0.954 (95% CI: 0.883 to 1.000; P<0.001) and the accuracy was 92.68%. Its sensitivity was 83.33% and the specificity was 96.55%. Conclusions: This method might be useful for thoracic surgeons during surgery, for its relatively high efficacy in rapid differentiation of LNs for patients with NSCLC.

Integrative pan cancer analysis reveals the importance of CFTR in lung adenocarcinoma prognosis.

Cystic fibrosis (CF) and cystic fibrosis transmembrane conductance regulator (CFTR) mutations have been shown to be associated with the risk of a variety of cancers. However, the clinical significance of aberrant CFTR gene expression in human tumors remains unknown. The expression profiles and prognostic landscapes of CFTR in human cancers were identified from the PubMed, OVID, CNKI, TCGA, ONCOMINE, PrognoScan, and GEPIA databases. Over 11, 000 cancer samples from the literature, GEPIA database, and PrognoScan database were included in this study. In general, CFTR has various expression and prognostic profiles in cancers, but the results from cross-database and meta-analyses revealed that CFTR is a robust biomarker for LUAD prognosis. Collectively, this study suggests that CFTR is an important prognostic biomarker for LUAD survival, implying that it could be used as a prognostic biomarker and therapeutic target for LUAD.

A Patient With a Foreign Body in Mediastinum That Penetrated Into the Bronchus.

We report the rare case of a patient who had a foreign body in the mediastinum and trachea caused by trauma due to epileptic seizures. A 52-year-old man had an epileptic seizure 3 months before visiting our hospital and had an injury to his neck caused by a broken glass cabinet. Computed tomography scan revealed a foreign body in the mediastinum and trachea. After a detailed discussion among members of the multidisciplinary team, surgery was successfully performed to remove the foreign body. This rare case may help provide a reference for diagnosing and treating a mediastinal and tracheobronchial foreign body.

Ideal Anatomical Landmark Points for Thoracic Esophagus Segmentation in the Chinese Population.

Introduction: The standards of esophagus segmentation remain different between the Japan Esophageal Society (JES) guideline and the Union for International Cancer Control (UICC)/American Joint Committee on Cancer (AJCC) guideline. This study aimed to present variations in the location of intrathoracic esophageal adjacent anatomical landmarks (EAALs) and determine an appropriate method for segmenting the thoracic esophagus based on the relatively fixed EAALs. Patients and Methods: The distances from the upper incisors to the upper border of the esophageal hiatus, lower border of the inferior pulmonary vein (LPV), tracheal bifurcation, lower border of the azygous vein (LAV), and thoracic inlet were measured in the patients undergoing thoracic surgery. The median distances between the EAALs and the specified starting points, as well as reference value ranges and ratios, were obtained. The variation coefficients of distances and ratios from certain starting points to different EAALs were calculated and compared to determine the relatively fixed landmarks. Results: This study included 305 patients. The average distance from the upper incisors to the upper border of the cardia, the midpoint between the tracheal bifurcation and esophageal hiatus (MTBEH), LPV, LAV, tracheal bifurcation, and thoracic inlet were 41.6, 35.3, 34.8, 29.4, 29.5, and 20.3 cm, respectively. The distances from the upper incisors or thoracic inlet to any intrathoracic EAALs in men were higher than in women. In addition, the height, weight, and body mass index (BMI) were correlated with the distances. The ratio of the distance between the upper incisors and tracheal bifurcation to the distance between the upper incisors and upper border of the cardia and the ratio of the distance between the thoracic inlet and tracheal bifurcation to the distance between the thoracic inlet and upper border of the cardia possessed relatively smaller coefficients of variation. Conclusion: The distances from the EAALs to the upper incisors vary with height, weight, BMI, and gender. Compared with distance, the ratios are more suitable for esophagus segmentation. Tracheal bifurcation and MTBEH are ideal EAALs for thoracic esophagus segmentation, and this is consistent with the JES guideline recommendation.

The first comprehensive database of germline pathogenic variants in East Asian cancer patients.

Pathogenic germline variants in cancer-associated genes are risk factors for cancer predisposition. However, systematic mining and summarizing of cancer pathogenic or likely pathogenic variants has not been performed for people of East Asian descent. This study aimed to investigate publicly available data to identify germline variants in East Asian cancer cohorts and compare them to variants in Caucasian cancer cohorts. Based on the data we retrieved, we built a comprehensive database, named COGVIC (Catalog of Germline Variants in Cancer). A total of 233 variants in the East Asian population were identified. The majority (87%) of genes with cancer-associated variants were not shared between the East Asian and Caucasian cohorts. This included pathogenic variants in BRCA2. Our study summarized the prevalence of germline variants in East Asian cancer cohorts and provides an easy-to-use online tool to explore germline mutations related to cancer susceptibility. DATABASE URL: http://www.cogvic.vip/.

m6A demethylase ALKBH5 suppression contributes to esophageal squamous cell carcinoma progression.

Esophageal squamous cell carcinoma (ESCC) is a highly malignant gastrointestinal cancer with a high recurrence rate and poor prognosis. Although N6-methyladenosine (m6A), the most abundant epitranscriptomic modification of mRNAs, has been implicated in several cancers, little is known about its participation in ESCC progression. We found reduced expression of ALKBH5, an m6A demethylase, in ESCC tissue specimens with a more pronounced effect in T3-T4, N1-N3, clinical stages III-IV, and histological grade III tumors, suggesting its involvement in advanced stages of ESCC. Exogenous expression of ALKBH5 inhibited the in vitro proliferation of ESCC cells, whereas depletion of endogenous ALKBH5 markedly enhanced ESCC cell proliferation in vitro. This suggests ALKBH5 exerts anti-proliferative effects on ESCC growth. Furthermore, ALKBH5 overexpression suppressed tumor growth of Eca-109 cells in nude mice; conversely, depletion of endogenous ALKBH5 accelerated tumor growth of TE-13 cells in vivo. The growth-inhibitory effects of ALKBH5 overexpression are partly attributed to a G1-phase arrest. In addition, ALKBH5 overexpression reduced the in vitro migration and invasion of ESCC cells. Altogether, our findings demonstrate that the loss of ALKBH5 expression contributes to ESCC malignancy.

Current Evidence of the Efficacy and Safety of Neoadjuvant EGFR-TKIs for Patients With Non-small Cell Lung Cancer.

PURPOSE: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have been indicated to be an effective treatment for advanced EGFR-mutant NSCLC. However, the neoadjuvant application of EGFR-TKIs in resectable NSCLC needs further investigation. Here, we aimed to evaluate the efficacy and safety of neoadjuvant EGFR-TKIs for lung cancer. METHODS: Published studies on neoadjuvant EGFR-TKIs in NSCLC were identified in PubMed, Web of Science, and EMBASE until June 1, 2020. Data on surgical rates, objective response rates (ORRs), pathologic responses, and adverse event (AE) rates were retrieved for proportional meta-analysis. RESULTS: In total, 7 enrolled studies involving 129 EGFR-TKI-sensitive NSCLC patients were included in this analysis. The overall surgical rate in these studies was 95% (95% CI: 83% to 100%), with an ORR of 48% (95% CI: 39% to 57%) in the population with EGFR-TKI-sensitive mutations, whereas the ORR including wild-type EGFR patients was 28% (95% CI: 14% to 44%). The rate of grade 1-2 AEs was 69% (95% CI: 41% to 91%) but with an acceptable rate of grade 3-4 AEs of 0% (95% CI: 0% to 5%). The pooled rates of rash and diarrhea were 56% (95% CI: 31% to 79%) and 25% (95% CI: 6% to 51%), respectively. The impact of neoadjuvant EGFR-TKIs on survival remains inconclusive. CONCLUSIONS: Neoadjuvant EGFR-TKIs showed objective responses in approximately half of EGFR-sensitive NSCLC patients with a tolerable adverse effect profile. The favorable impact of neoadjuvant EGFR-TKIs on NSCLC needs more evidence for validation, such as the comparison of survival improvement between EGFR-TKIs and chemotherapy. The efficacy of neoadjuvant next-generation EGFR-TKIs in clinical trials remains unclear.

Lung segmentectomy assisted by highly selective independent segmental ventilation: a series of three cases.

BACKGROUND: The identification of targeted intersegmental planes and resection with adequate surgical margins are among the crucial steps in anatomical pulmonary segmentectomy, and technical improvements are still needed. CASE PRESENTATION: We reported three cases of intersegmental plane identification using highly selective independent segmental ventilation during segmentectomy. All cases required cooperation with an anesthesiologist who was able to perform segmental ventilation and double confirmation of segmental bronchus branches by the surgeon. The surgical procedure provides a direct visualization of spare segment inflation and saves time in deflation over the conventional residual segment inflation method. CONCLUSIONS: Highly selective independent segmental ventilation could be considered a suitable option for pulmonary intersegmental plane identification and could be universally used for lung segmentectomy.

Delivery of gefitinib with an immunostimulatory nanocarrier improves therapeutic efficacy in lung cancer.

BACKGROUND: Combining different cancer treatments represents a promising strategy to improve the therapeutic outcome for lung cancer patients with or without druggable gene alterations. METHODS: We previously developed a polyethylene glycol-based (PEG-based) immunostimulatory nanocarrier (PEG2k-Fmoc-NLG919) which can efficiently co-deliver an indoleamine 2,3-dioxygenase-1 (IDO1) inhibitor and the chemotherapeutic agent, paclitaxel. This method was found to improve cancer therapy by simultaneously performing immuno- and chemo-therapy. However, whether this nanocarrier could deliver targeted drugs to implement targeted therapy together with immunotherapy remains unclear. RESULTS: Here, we report that the delivery of the classical tyrosine kinase inhibitor (TKI), gefitinib, with the optimized PEG5k-Fmoc-NLG919 nanocarrier, increased the sensitivity of lung cancer cells to gefitinib in vitro. Gefitinib was gradually but sufficiently released from the nanocarrier with comparable capacity to inhibit epidermal growth factor receptor (EGFR) activity as using free gefitinib directly. More importantly, treatment with gefitinib-loaded PEG5k-Fmoc-NLG919 could suppress lung tumor development more efficiently than gefitinib alone in vivo by inducing an immune active microenvironment with more functional CD8+ T cells and less regulatory T cell infiltration. CONCLUSIONS: Our study therefore demonstrates that delivery of small molecular targeted drugs with the immunostimulatory nanocarrier is a straightforward strategy for improving antitumor response for lung cancer therapy.

Classification of Metastatic and Non-Metastatic Thoracic Lymph Nodes in Lung Cancer Patients Based on Dielectric Properties Using Adaptive Probabilistic Neural Networks.

OBJECTIVE: Dielectric properties can be used in normal and malignant tissue identification, which requires an effective classifier because of the high throughput nature of the data. With easy training and fast convergence, probabilistic neural networks (PNNs) are widely applied in pattern classification problems. This study aims to propose a classifier to identify metastatic and non-metastatic thoracic lymph nodes in lung cancer patients based on dielectric properties. METHODS: The dielectric properties (permittivity and conductivity) of lymph nodes were measured using an open-ended coaxial probe. The Synthetic Minority Oversampling Technique method was adopted to modify the dataset. Feature parameters were scored to select the appropriate feature vector using a Statistical Dependency algorithm. The dataset was classified using adaptive PNNs with an optimized smooth factor using the simulated annealing PNN (SA-PNN). The results were compared with traditional Probabilistic, Support Vector Machines, k-Nearest Neighbor and the Classify functions in MATLAB. RESULTS: The conductivity frequencies of 3959, 3958, 3960, 3978, 3510, 3889, 3888, and 3976 MHz were selected as the feature vectors for 219 lymph nodes (178 non-metastatic and 41 metastatic). Compared with the other methods, SA-PNN achieved the highest classification accuracy (92.92%) and the corresponding specificity and sensitivity were 94.72% and 91.11%, respectively. CONCLUSIONS: Compared with the other methods, the SA-PNN proposed in the present study achieved a higher classification accuracy, which provides a new scheme for classification of metastatic and non-metastatic thoracic lymph nodes in lung cancer patients based on dielectric properties.

Clinicopathological features, survival outcomes, and appropriate surgical approaches for stage I acinar and papillary predominant lung adenocarcinoma.

BACKGROUND: Whether prognosis differs between lung acinar predominant adenocarcinoma (ACN) and papillary predominant adenocarcinoma (PAP) patients remains controversial. Furthermore, the appropriate surgical plan for each subtype is undetermined. METHODS: Data of stage I ACN or PAP patients from 2004 to 2015 were retrospectively reviewed by SEER*Stat 8.3.5. The primary outcome was overall survival (OS) and lung cancer specific survival (LCSS). RESULTS: 1531 patients (PAP, 484; ACN, 1047) were included. ACN patients had better OS (P = .001) and LCSS (P = .003) than PAP patients. Among stage I ACN patients, lobectomy with mediastinal lymph node dissection (Lob) (P = .001) or segmentectomy (Seg) (P = .003) provided a better OS than wedge resection (Wed). And ACN patients who received Lob had a equivalent LCSS, compared to those who received Seg (P = .895). For patients with PAP in stage I, those who received Lob tended to have a better prognosis than that received Seg (HR of OS, 0.605, 95% CI: 0.263-1.393; HR of LCSS, 0.541, 95% CI: 0.194-1.504) or Wed (HR of OS, 0.735, 95% CI: 0.481-1.123; HR of LCSS, 0.688, 95% CI: 0.402-1.180). CONCLUSIONS: Among patients with lung adenocarcinoma in stage I, those with ACN have a better OS and LCSS than that with PAP. For patients with stage I ACN, Seg and Lob, rather than Wed, seem to be an equivalent treatment choice; however, Seg is the prior option because it could preserve more lung function than Lob. For patients with PAP, Lob tends to be a better choice than Wed and Seg, although the prognostic difference between them is nonsignificant.

Beyond T Cells: Understanding the Role of PD-1/PD-L1 in Tumor-Associated Macrophages.

Programmed cell death protein 1 (PD-1) and its ligand PD-L1 have attracted wide attention from researchers in the field of immunotherapy. PD-1/PD-L1 have been shown to exist in many types of cells in addition to T lymphocytes, and studies have accordingly extended from their suppressive effect on T cell activation and function to examining their role in other cells. In this review, we summarize recent research on PD-1/PD-L1 in macrophages, with the aim of furthering our understanding of PD-1/PD-L1 and their detailed roles in macrophages. This information may provide additional insights for researchers, enrich the basic theory of anti-PD-1/PD-L1 immunotherapy, and thus ultimately benefit more patients.

TUSC3 accelerates cancer growth and induces epithelial-mesenchymal transition by upregulating claudin-1 in non-small-cell lung cancer cells.

Lung cancer is the most frequent cause of cancer-related deaths worldwide, but its molecular pathogenesis is poorly understood. The tumor suppressor candidate 3 (TUSC3) gene is located on chromosome 8p22 and is universally acknowledged as a cancer suppressor. However, our research has demonstrated that TUSC3 expression is significantly upregulated in non-small-cell lung cancer compared to benign controls. In this study, we analyzed the consequences of TUSC3 knockdown or overexpression on the biological functions of non-small-cell lung cancer cell lines. To identify the molecules and signaling pathways with which TUSC3 might interact, we completed immunoblotting, quantitative polymerase chain reaction, microarray, co-immunoprecipitation, and immunofluorescence assays. We demonstrated that TUSC3 knockdown leads to decreased proliferation, migration, and invasion, and reduced xenograft tumor growth of non-small-cell lung cancer cell lines, whereas opposite results were observed with overexpression of TUSC3. In addition, TUSC3 knockdown suppressed epithelial-mesenchymal transition by downregulating the expression of claudin-1, which plays an indispensable role in EMT progress. On the contrary, overexpression of TUSC3 significantly enhanced EMT progress by upregulating claudin-1 expression. Overall, our observations suggest that TUSC3 accelerates cancer growth and induces the epithelial-mesenchymal transition in non-small-cell lung cancer cells; we also identified claudin-1 as a target of TUSC3.