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Background: Lung cancer remains the foremost reason of cancer‐related mortality, with invasion and metastasis profoundly influencing patient prognosis. N‐acetyltransferase 10 (NAT10) catalyzes the exclusive N (4)‐acetylcytidine (ac4C) modification in eukaryotic RNA. NAT10 dysregulation is linked to various diseases, yet its role in non‐small cell lung cancer (NSCLC) invasion and metastasis remains unclear. Our study delves into the clinical significance and functional aspects of NAT10 in NSCLC. Methods: We investigated NAT10's clinical relevance using The Cancer Genome Atlas (TCGA) and a group of 98 NSCLC patients. Employing WB, qRT‐PCR, and IHC analyses, we assessed NAT10 expression in NSCLC tissues, bronchial epithelial cells (BECs), NSCLC cell lines, and mouse xenografts. Further, knockdown and overexpression techniques (siRNA, shRNA, and plasmid) were employed to evaluate NAT10's effects. A series of assays were carried out, including CCK‐8, colony formation, wound healing, and transwell assays, to elucidate NAT10's role in proliferation, invasion, and metastasis. Additionally, we utilized lung cancer patient‐derived 3D organoids, mouse xenograft models, and Remodelin (NAT10 inhibitor) to corroborate these findings. Results: Our investigations revealed high NAT10 expression in NSCLC tissues, cell lines and mouse xenograft models. High NAT10 level correlated with advanced T stage, lymph node metastasis and poor overall survive. NAT10 knockdown curtailed proliferation, invasion, and migration, whereas NAT10 overexpression yielded contrary effects. Furthermore, diminished NAT10 levels correlated with increased E‐cadherin level whereas decreased N‐cadherin and vimentin expressions, while heightened NAT10 expression displayed contrasting results. Notably, Remodelin efficiently attenuated NSCLC proliferation, invasion, and migration by inhibiting NAT10 through the epithelial‐mesenchymal transition (EMT) pathway. Conclusions: Our data underscore NAT10 as a potential therapeutic target for NSCLC, presenting avenues for targeted intervention against lung cancer through NAT10 inhibition. [ABSTRACT FROM AUTHOR]

Malignant mesothelioma, a rare and aggressive cancer primarily caused by occupational asbestos exposure, has a poor prognosis. This study leverages the Global Burden of Disease (GBD) 2019 dataset to analyze the burden of mesothelioma linked to occupational asbestos exposure from 1990 to 2019. The analysis includes the number of mesothelioma deaths and disability-adjusted life years (DALYs) attributable to occupational asbestos exposure, focusing on trends in age-standardized mortality rate (ASMR) and age-standardized disability-adjusted life-year rate (ASDR) by year, age, sex, country, region, and Socio-demographic Index (SDI). In 2019, 91.7% of mesothelioma deaths and 85.2% of DALYs were attributable to occupational asbestos exposure, resulting in 26,820 (95% UI 24,312–28,622) deaths and 569,429 (95% UI 509,956–617,484) DALYs. Despite a decline in ASMR and ASDR from 1990 to 2019, the absolute number of deaths and DALYs almost doubled. The United States reported the highest number of mesothelioma deaths, while China had the highest number of DALYs. Age-specific mortality rates and DALYs decreased in the 25–74 age group but increased in the 75+ age group. In conclusion, occupational asbestos exposure remains the primary cause of mesothelioma worldwide, with an increasing number of deaths and DALYs. The highest incidence rates are observed in high-income areas, and rates are rising in low-income areas. It is crucial to raise awareness about the hazards of asbestos to reduce the global burden of mesothelioma linked to occupational exposure. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In this study, we investigated the expression patterns and functional roles of microRNA 127 (miR-127) and its target gene Formin-Like 3 (FMNL3) in human esophageal squamous cell carcinoma (ESCC). Quantitative RT-PCR (qRT-PCR) was used to compare miR-127 expression between ESCC cell lines and normal esophageal epithelium cell line, as well as paired ESCC tumors and adjacent normal esophageal tissues in 33 patients. We found miR-127 was aberrantly downregulated in both ESCC cell lines and human ESCC tumors. In ESCC cell lines TE-1 and ECA109 cells, lentiviral-induced miR-127 upregulation markedly inhibited cancer proliferation and migration in vitro , and tumorigenicity in vivo. Through dual-luciferase assay and qRT-PCR, FMNL3 was confirmed to be the downstream target gene of miR-127 in ESCC. Finally, FMNL3 was downregulated by siRNA in TE-1 and ECA109 cells. And we discovered that SiRNA-induced FMNL3 downregulation had tumor suppressive effect in ESCC, inhibiting cancer proliferation, migration in vitro , and tumorigenicity in vivo. These results suggest that miR-127 is downregulated and acting as tumor suppressor in ESCC. Inversely, FMNL3, the target gene of miR-127, is upregulated and acting as an oncogene in ESCC. [ABSTRACT FROM AUTHOR]

Long noncoding ribonucleic acids (RNAs; LncRNAs) endowed with both protein-coding and noncoding functions are referred to as 'dual functional lncRNAs'. Recently, dual functional lncRNAs have been intensively studied and identified as involved in various fundamental cellular processes. However, apart from time-consuming and cell-type-specific experiments, there is virtually no in silico method for predicting the identity of dual functional lncRNAs. Here, we developed a deep-learning model with a multi-head self-attention mechanism, LncReader, to identify dual functional lncRNAs. Our data demonstrated that LncReader showed multiple advantages compared to various classical machine learning methods using benchmark datasets from our previously reported cncRNAdb project. Moreover, to obtain independent in-house datasets for robust testing, mass spectrometry proteomics combined with RNA-seq and Ribo-seq were applied in four leukaemia cell lines, which further confirmed that LncReader achieved the best performance compared to other tools. Therefore, LncReader provides an accurate and practical tool that enables fast dual functional lncRNA identification. [ABSTRACT FROM AUTHOR]

Background: Esophageal carcinoma is one of the most fatal cancers worldwide. In China, over 90% of esophageal cancer patients are diagnosed with esophageal squamous cell carcinoma (ESCC). Currently, the survival and prognosis of ESCC patients are not satisfying because of insufficient early screening and lack of efficacious medication. Accumulating studies have suggested that antibody‐drug conjugates (ADC) represent a promising antitumor strategy. Method: Here, we carried out a specific membrane proteome screening with ESCC patients' samples using a high‐throughput antibody microarray to uncover potential targets for ADC development. Candidates were validated with expression and cytotoxicity evaluation both in vitro and in vivo. Results: Our data have shown that the Piezo‐Type Mechanosensitive Ion Channel Component 1 (PIEZO1) is particularly overexpressed in human ESCC tumors and can be efficiently internalized when bound with its monoclonal antibody. Furthermore, the PIEZO1 antibody combined with monomethyl auristatin E (MMAE) can specifically kill PIEZO1 high‐expressed ESCC tumor cells by inducing cell cycle arrest and apoptosis. More importantly, the Anti‐PIEZO1‐MMAE can significantly suppress tumor progression in ESCC xenograft tumor models without any obvious side effects. Conclusion: Taken together, our work demonstrates that PIEZO1 is a promising target to develop ADCs for human ESCC treatment, providing a new strategy for ESCC patients' personalized therapy. [ABSTRACT FROM AUTHOR]

Background: Epidermal growth factor receptor (EGFR) mutations occur in up to 50% of Asian patients with non-small cell lung cancer (NSCLC). Treatment of advanced NSCLC patients with EGFR-tyrosine kinase inhibitor (EGFR-TKI) confers a significant survival benefit. This study assessed the efficacy and safety of chemotherapy with or without icotinib in patients undergoing resection of stage IB to ⅢA EGFR-mutated NSCLC. Methods: Patients with surgically resected stage IB (with high risk factors) to ⅢA EGFR-mutated NSCLC were randomly assigned (1:1) to one of two treatment plans. One group received four cycles of platinum-based doublet chemotherapy every three weeks, and the other group received platinum-based chemotherapy supplemented with consolidation therapy of orally administered icotinib (125 mg thrice daily) two weeks after chemotherapy. The icotinib treatment continued for four to eight months, or until the occurrence of disease relapse, metastasis or unacceptable icotinib or chemotherapy toxicity. The primary endpoint was disease-free survival (DFS). Results: 41 patients were enrolled between Feb 9, 2011 and Dec 17, 2012. 21 patients were assigned to the combined chemotherapy plus icotinib treatment group, while 20 patients received chemotherapy only. DFS at 12 months was 100% for icotinib-treated patients and 88.9% for chemotherapy-only patients (p = 0. 122). At 18 months DFS for icotinib-treated vs. chemotherapy-only patients was 95.2% vs. 83.3% (p = 0. 225), respectively, and at 24 months DFS was 90.5% vs. 66.7% (p = 0. 066). The adverse chemotherapy effects predominantly presented as gastrointestinal reactions and marrow suppression, and there was no significant difference between the two treatment groups. Patients in the chemotherapy plus icotinib treatment group showed favorable tolerance to oral icotinib. Conclusions: The results suggest that chemotherapy plus orally icotinib displayed better DFS compared with chemotherapy only, yet the difference in DFS was not significant. We would think the preliminary result here was promising, and further trials with larger sample sizes might confirm the efficiency of adjuvant TKI in selected patients. Trial Registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

We conducted a proof-of-concept, phase 2 trial to assess neoadjuvant SHR-1701 with or without chemotherapy, followed by surgery or radiotherapy, and then consolidation SHR-1701 in unresectable stage III non-small-cell lung cancer (NSCLC). In the primary cohort of patients receiving neoadjuvant combination therapy (n = 97), both primary endpoints were met, with a post-induction objective response rate of 58% (95% confidence interval [CI] 47–68) and an 18-month event-free survival (EFS) rate of 56.6% (95% CI 45.2–66.5). Overall, 27 (25%) patients underwent surgery; all achieved R0 resection. Among them, 12 (44%) major pathological responses and seven (26%) pathological complete responses were recorded. The 18-month EFS rate was 74.1% (95% CI 53.2–86.7) in surgical patients and 57.3% (43.0–69.3) in radiotherapy-treated patients. Neoadjuvant SHR-1701 with chemotherapy, followed by surgery or radiotherapy, showed promising efficacy with a tolerable safety profile in unresectable stage III NSCLC. Surgical conversion was feasible in a notable proportion of patients and associated with better survival outcomes. [Display omitted] • Design: neoadjuvant SHR-1701±chemo, then surgery/RT in stage III unresectable NSCLC • Primary cohort (neoadjuvant combo): post-induction ORR 58%; 18-month EFS 56.6% • Surgery conversion: 25%, all R0 resection • Surgical set: MPR 44%; pCR 26%; 18-month EFS 74.1% (vs. 57.3% in RT set) Zhou et al. evaluated neoadjuvant SHR-1701 with chemotherapy, followed by surgery or radiotherapy in treating unresectable stage III NSCLC in a phase 2 trial. The regimen demonstrated promising anti-tumor activity with an acceptable safety profile. Surgical conversion after neoadjuvant treatment was feasible and was associated with better survival outcomes. [ABSTRACT FROM AUTHOR]

Background: Circular RNA (circRNA) has been recently identified as a critical regulator during carcinogenesis. However, the biological function and potential underlying mechanisms of circRNAs in lung cancer remain to be further elucidated. Methods: Here, we first evaluated the differentially expressed circRNAs between tumor and the matched adjacent nontumor tissues (3 pairs) of lung cancer patients via circRNA microarray. The expression of top five dysregulated circRNAs were tested in lung cancer cell lines and the circSCAP with concordant alteration in microarray data and cell lines was selected for further investigation. Then we validated the expression level of circSCAP in tumor and corresponding adjacent tissues (161 pairs) from a lung cancer cohort by RT-PCR analysis followed by correlation and prognosis analysis between circSCAP and clinical characteristics. Non-small cell lung cancer (NSCLC) accounts for the majority of lung cancer diagnosis (about 80% in the cohort used in this study). Therefore, we focused the role of circSCAP in NSCLC in the present study. In vitro and in vivo assays were performed to study the biological function of circSCAP in NSCLC. Biotin-labeled RNA pulldown and RNA immunoprecipitation (RIP) assays were carried out to identify the proteins directly interacting with circSCAP. The molecular mechanism of circSCAP-driven tumor suppression was demonstrated by immunoblotting, immunoprecipitation and luciferase reporter assays. In vitro and in vivo rescue experiments were conducted to verify the role of the circSCAP/SF3A3/p53 signaling axis in NSCLC. Results: We screened the expression profiles of human circRNAs in lung cancer tissues and found that hsa_circ_0065214 (termed as circSCAP) was significantly decreased. Kaplan–Meier analysis showed that patients with low level of circSCAP had a significantly poor prognosis. Gain- and loss-of-function experiments suggested that circSCAP played an important role in NSCLC cell proliferation, cell migration and apoptosis. Mechanistically, circSCAP directly binds to the SF3A3 protein, facilitating the reduction of SF3A3 by promoting its ubiquitin–proteasome-mediated degradation, which enhances the expression of MDM4-S to finally activate its downstream p53 signaling. Conclusion: These findings illustrate a novel circSCAP/SF3A3/p53 signaling axis involved in suppressing the malignance of NSCLC and provide a promising target for NSCLC prognosis prediction and treatment. [ABSTRACT FROM AUTHOR]

Objective Esophageal carcinoma (ESCA) is deadly cancer worldwide with unknown etiology. This study aimed to investigate the impact and mechanism of RAD6 on the development of Esophageal squamous cell carcinoma (ESCC). Expressions of RAD6A and RAD6B in ESCA were investigated from TCGA dataset and their expressions in tissue sample of ESCA patients and cells were determined. Functional experiments were conducted to explore the impact of RAD6A and RAD6B on malignant characteristics of several kinds of ESCC cells. Animal experiment was established and injected with RAD6A and RAD6B shRNA to evaluate the effect on tumor growth. RAD6A and RAD6B were up-regulated in ESCC cells and tissues. Overexpressed RAD6A and RAD6B similarly increased ESCC cell proliferation, invasion and migration and silencing of RAD6 exerted opposite effects. Knockdown of RAD6A suppressed tumor growth and decreased the level of H2B, as data demonstrated positive correlation between RAD6A and CCNB1 in ESCC tissues. Collectively, this study elucidates that RAD6 is up-regulated in ESCC and promotes the progression of ESCC through up-regulation of CCNB1 to enhance H2B ubiquitination. These evidence provide a novel insight into the pathogenesis of ESCC and might contribute to the development of targeted therapy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The tumour microenvironment primarily constitutes macrophages in the form of an immunosuppressive M2 phenotype, which promotes tumour growth. Thus, the development of methodologies to rewire M2‐like tumour‐associated macrophages (TAMs) into the M1 phenotype, which inhibits tumour growth, might be a critical advancement in cancer immunotherapy research. Methods: The expressions of IL‐33 and indicators related to macrophage polarization in oesophageal squamous cell carcinoma (ESCC) tissues and peripheral blood mononuclear cell (PBMC)–derived macrophages were determined. Inhibition of ornithine decarboxylase (ODC) with small interfering RNA was used to analyse the phenotype of macrophage polarization and polyamine secretory signals. CCK‐8, wound‐healing and Transwell assays were used to detect the proliferation and migration of ECA109 cells in vitro. The tumour xenograft assay in nude mice was used to examine the role of IL‐33 in ESCC development in vivo. Results: This study showed the substantially elevated IL‐33 expression in ESCC tissues compared with the normal tissues. Additionally, enhanced infiltration of M2‐like macrophages into the ESCC tumour tissue was also observed. We observed a strong correlation between the IL‐33 levels and the infiltration of M2‐like macrophages in ESCC tumours locally. Mechanistically, IL‐33 induces M2‐like macrophage polarization by activating ODC, a key enzyme that catalyses the synthesis of polyamines. Inhibition of ODC suppressed M2‐like macrophage polarization. Finally, in vivo, we confirmed that IL‐33 promotes tumour progression. Conclusions: This study revealed an oncogenic role of IL‐33 by actively inducing M2‐like macrophage differentiation; thus, contributing to the formation of an immunosuppressive ESCC tumour microenvironment. Thus, IL‐33 could act as a novel target for cancer immunotherapies. [ABSTRACT FROM AUTHOR]

Introduction: Owing to its involvement in both the initiation and progression of various cancers, aberrant circular RNA (circRNA) expression has been researched extensively in the recent times. In the present study, we aim to investigate the effect of a novel circRNA has_circ_0025933 (circNELL2) in the progression of esophageal squamous cell carcinoma (ESCC). Materials and Methods: Sanger sequencing and the detection of circNELL2 level after RNase R or actinomycin D treatment were performed to identify the existence of cirNELL2 in ESCC cells. WST, EDU staining and colony-formation assay were used to assess the proliferation while transwell assay was used to evaluate the migration of ESCC cells. Luciferase assay, RNA pull down and the FISH assay were performed to verify the interaction between circNELL2 and miR-127-5p as well as miR-127-5p and CDC6. Xenograft model was carried out to evaluate the effect of circNELL2 in vivo. Results: circNELL2 was proved to exist in ESCC cells. The up-regulated expression of circNELL2 in the clinical ESCC specimens was also verified. Next, function studies suggested that circNELL2 knockdown inhibited the proliferation of ESCC cells in vitro and in vivo, while circNELL2 overexpression promotes that of ESCC cells. Besides, this study mechanically predicted and verified the target miR of circNELL2, which is miR-127-5p. It was found that miR-127-5p was capable of reversing the effect of circNELL2 on ESCC cells. Moreover, miR-127-5p was also found to target CDC6 to participate in the regulation of cell phenotype. Discussion: circNELL2 promoted the progression of ESCC cells via sponging miR-127-5p, and it has the potential to serve as a novel prognostic and therapeutic target for ESCC. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Tumour cells interfere with normal immune functions by affecting the expression of some immune-related genes, which play roles in the prognosis of cancer patients. In recent years, immunotherapy for tumours has been widely studied, but a practical prognostic model based on immune-related genes in lung adenocarcinoma comparable to existing model has not been established and reported.Methods: We first obtained publicly accessible lung adenocarcinoma RNA expression data from The Cancer Genome Atlas (TCGA) for differential gene expression analysis and then filtered immune-related genes based on the ImmPort database. By using the lasso algorithm and multivariate Cox Proportional-Hazards (CoxPH) regression analysis, we identified candidate genes for model development and validation. The robustness of the model was further examined by comparing the model with three established gene models.Results: Gene expression data from a total of 524 lung adenocarcinoma patients from TCGA were used for model development. We identified four biomarkers (MAP3K8, CCL20, VEGFC, and ANGPTL4) that could predict overall survival in lung adenocarcinoma (HR = 1.98, 95% CI 1.48 to 2.64, P = 4.19e-06) and this model could be used as a classifier for the evaluation of low-risk and high-risk groups. This model was validated with independent microarray data and was highly comparable with previously reported gene expression signatures for lung adenocarcinoma prognosis.Conclusions: In this study, we identified a practical and robust four-gene prognostic model based on an immune gene dataset with cross-platform compatibility. This model has potential value in improving TNM staging for survival predictions in patients with lung adenocarcinoma.Impact: The study provides a method of immune relevant gene prognosis model and the identification of immune gene classifier for the prediction of lung adenocarcinoma prognosis with RNA sequencing and microarray compatibility. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The present study aimed to identify the novel biomarkers and underlying molecular mechanisms of lung adenocarcinoma (LAC) to aid in its diagnosis, prognosis, prediction, disease monitoring and emerging therapies. Data from a total of 498 LAC samples were collected from The Cancer Genome Atlas and divided into two sets by stratified randomization based on pathological Tumor-Node-Metastasis stage. The training set was comprised of 348 samples and the validation set was comprised of 150 samples. A total of 123 samples from the training set for patients who completed follow-up were analyzed by weighted gene co-expression network analysis. A module was identified that contained 113 protein-coding genes that were positively associated with overall survival (OS). A least absolute shrinkage and selection operator (LASSO) Cox regression model was constructed and four survival-associated genes (OPN3, GALNT2, FAM83A and KYNU) were retained. Risk score, calculated by the linear combination of each gene expression multiplied by the LASSO coefficient, could successfully discriminate between patients with LAC exhibiting low and high OS time in both sets. The results from the present study indicate that this risk score may contribute to potential diagnostic and therapeutic strategies for LAC management. [ABSTRACT FROM AUTHOR]

Background: Small cell lung cancer (SCLC) is a highly invasive and lethal neuroendocrine tumor. Antiangiogenic drugs have been reported in the treatment of SCLC. We aimed to provide a comprehensive evaluation of the impact of angiogenic inhibitors on SCLC survival using network meta‐analysis. Methods: The impact of five angiogenesis inhibitors, that is, vandetanib (Van), bevacizumab (Bev), Rh‐endostatin (End), sunitinib (Sun), and thalidomide (Tha), on progression‐free survival (PFS) and overall survival (OS) was evaluated by conducting a network meta‐analysis. RNA sequencing data were downloaded from publicly available databases. Results: Nine phase II and III randomized controlled trials (RCTs), that involved 1599 participants, that investigated angiogenesis inhibitors in the treatment of SCLC were included in this meta‐analysis. Sun and Bev achieved better PFS than Tha (Bev VS. Tha, HR = 0.88, 95% CI: 0.79‐0.98, Sun VS. Tha, HR = 0.80, 95% CI: 0.65‐1.00). Moreover, Sun and Bev were superior to placebo in terms of PFS (Bev VS. Placebo, HR = 0.89, 95%CI: 0.81‐0.97, Sun VS. Placebo, HR = 0.81, 95% CI: 0.66‐1.00). Based on this study, we found no significant difference of OS of SCLC. The angiogenesis pathway and expression of target genes were globally deactivated in SCLC tissue. Conclusion: Results of this network meta‐analysis indicate that the PFS outcome of SCLC with Sun or Bev drugs is superior to that of Tha. The improved therapeutic impact of angiogenesis inhibitors on SCLC needs more evidence, such as long‐term observation in clinical trials, to be validated. [ABSTRACT FROM AUTHOR]

Abstract 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. [ABSTRACT FROM AUTHOR]

Interleukin‑12 receptor (IL‑12R) and p38 mitogen‑activated protein kinase (p38MAPK) serve an important role in non‑small cell lung cancer (NSCLC). It has previously been suggested that IL‑12Rβ2 may be involved in key regulatory pathways and interacts with the p38MAPK signaling pathway. The present study aimed to elucidate the possible association and roles of IL‑12Rβ2 and p38MAPK in NSCLC. The protein expression levels of IL‑12Rβ2 and p38MAPK were measured in 230 NSCLC tissue samples by immunohistochemistry (IHC) and western blot analyses. In addition, an immunofluorescence assay was used to observe the expression levels of these proteins in A549 and H358 cells. The associations between IL‑12Rβ2, p38MAPK and clinical characteristics, were evaluated by Pearson χ2 and Spearman correlation tests. Kaplan‑Meier plots (log‑rank test) and Cox proportional hazard models were used to analyze overall survival (OS). Compared with in benign pulmonary tissues, the expression levels of IL‑12Rβ2 and p38MAPK were not demonstrated to be significantly different in I+II pathological tumor‑node‑metastasis (pTNM) stage NSCLC tissues; however, reduced expression was detected in III+IV pTNM stage NSCLC tissues. Analysis of the association between advanced stage pTNM and the expression of both proteins demonstrated a significantly decreased Allred score (both P<0.0001), which was confirmed by IHC and western blot analyses. The IHC results demonstrated a significant correlation between IL‑12Rβ2 and p38MAPK expression (r=0.415, P=0.0143). By analyzing IL‑12Rβ2, p38MAPK expression and clinical characteristics, it was identified that IL‑12Rβ2 was significantly associated with gender (P=0.0168), age (P=0.0341), histological type (P<0.0001) and pTNM stage (P<0.0001). p38MAPK demonstrated a strong association with gender (P=0.0082) and pTNM stage (P<0.0001). The results of a Kaplan‑Meier analysis indicated that positive IL‑12Rβ2 and p38MAPK expression was associated with increased OS compared with negative protein expression. The Cox proportional hazard models revealed that IL‑12Rβ2 and p38MAPK predicted a long OS. To the best of our knowledge, the present study is the first to reveal a close association between IL‑12Rβ2 and p38MAPK, and their possible function in NSCLC progression. It further demonstrated that expression of both proteins was lower with advanced pTNM staging, whereas a high expression of both proteins was associated with improved prognosis in NSCLC. [ABSTRACT FROM AUTHOR]

Micropapillary or solid pattern predicts recurrence free survival benefit from adjuvant chemotherapy in patients with stage IB lung adenocarcinoma. Some concerns were raised related to our study in the comments, which was published earlier in Cancer Medicine "Clinicopathological features, survival outcomes, and appropriate surgical approaches for stage I acinar and papillary predominant lung adenocarcinoma" (Article ID: CAM43012, Article DOI: 10.1002/cam4.3012, Internal Article ID: 16708831). Adjuvant chemotherapy improves the probability of freedom from recurrence in patients with resected stage IB lung adenocarcinoma. [Extracted from the article]

Non-small cell lung cancer (NSCLC) represents 75–80% of all lung carcinomas, which is the most common cause of death from cancer. Tumour suppressor candidate 3 (TUSC3) is pivotal in many biochemical functions and cytological processes. Dis-regulation of TUSC3 is frequently observed in epithelial cancers. In this study, we observed up-regulated TUSC3 expression at the mRNA and protein levels in clinical NSCLC samples compared with adjacent non-tumorous lung tissues. The expression level of TUSC3 is significantly correlated with tumour metastasis and patient survival. Overexpression of TUSC3 in NSCLC cells led to increased proliferation, migration, and invasion in vitro and accelerated xenograft tumour growth in vivo, while the opposite effects were achieved in TUSC3-silenced cells. Increased GLI1, SMO, PTCH1, and PTCH2 abundance were observed in TUSC3 overexpressed cells using western blotting. Co-immunoprecipitation and immunofluorescence analyses further revealed interaction between TUSC3 and GLI1. In conclusion, our study demonstrated an oncogenic role of TUSC3 in NSCLC and showed that dis-regulation of TUSC3 may affect tumour cell invasion and migration through possible involvement in the Hedgehog (Hh) signalling pathway. [ABSTRACT FROM AUTHOR]

• A novel 3D printing flexible PEEK chest wall implant was designed. • Flexible implant provides excellent stiffness and strength under the chest compression. • The mechanical properties of complete flexible implant under the dynamic impact and fatigue testing were investigated. • The flexible implant can effectively restore the respiratory function in vivo. Rigid reconstruction of chest wall defect seriously affects the postoperative respiratory owing to neglecting the functional role of natural costal cartilage. In the study, a 3D printing PEEK flexible implant was developed to restore the deformation capability during breathing motion. Bionic spring structures in different region of implant were designed by taking into consideration of the anatomical morphology and materials properties of costal cartilage. The biomechanical properties of the rigid and flexible implants under the chest compression were compared through the finite element analysis. Two kinds of chest wall implant samples were fabricated with fused deposition modeling (FDM) technology to evaluate experimentally the mechanical behaviors. Finally, the restoration ability of respiratory function from the flexible implant was investigated in vivo. The flexible implant exhibited the similar stiffness to the natural thorax and satisfied the strength demand in the chest compression. The maximal impact force of flexible implant reached to 536 N. The fatigue failure of complete flexible implant was revealed from the initiation and propagation of interlaminar crack to the fracture in a zigzag manner. Animal experiments validated that the parameters characterizing respiratory could be recovered to the preoperative and normal state. In the study, the flexible implant provided these advantages for perfect replication of thoracic shape, reliable safety, and great deformation capability to response respiratory movement, which given a superior treatment for chest wall reconstruction. [Display omitted] [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor (EGFR) mutations are the strongest response predictors to EGFR tyrosine kinase inhibitors (TKI) therapy, but knowledge of the EGFR mutation frequency on lung adenocarcinoma is still limited to retrospective studies. The PIONEER study (NCT01185314) is a prospective molecular epidemiology study in Asian patients with newly diagnosed advanced lung adenocarcinoma, aiming to prospectively analyze EGFR mutation status in IIIB/IV treatment-naïve lung adenocarcinomas in Asia. We report the mainland China subset results. Eligible patients (≥20 yrs old, IIIB/IV adenocarcinoma and treatment-naïve) were registered in 17 hospitals in mainland China. EGFR was tested for mutations by amplification refractory mutation system using biopsy samples. Demographic and clinical characteristics were collected for subgroup analyses. A total of 747 patients were registered. Successful EGFR mutation analysis was performed in 741, with an overall mutation rate of 50.2%. The EGFR active mutation rate is 48.0% (with 1.3% of combined active and resistance mutations). Tobacco use (>30 pack-year vs. 0–10 pack-year, OR 0.27, 95%CI: 0.17–0.42) and regional lymph nodes involvement (N3 vs. N0, OR 0.47, 95%CI: 0.29–0.76) were independent predictors of EGFR mutation in multivariate analysis. However, even in regular smokers, the EGFR mutation frequency was 35.3%. The EGFR mutation frequency was similar between diverse biopsy sites and techniques. The overall EGFR mutation frequency of the mainland China subset was 50.2%, independently associated with the intensity of tobacco use and regional lymph nodes involvement. The relatively high frequency of EGFR mutations in the mainland China subset suggest that any effort to obtain tissue sample for EGFR mutation testing should be encouraged. [ABSTRACT FROM AUTHOR]

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. • An integrative cross-database bioinformatic approach to study potential targets for cancer diagnosis and prognosis. • The role of CFTR expression in over 11, 000 cancer samples from multiple datasets were analyzed; • CFTR has various expression profiles in cancers; • CFTR is a promising biomarker for lung adenocarcinoma prognosis. [ABSTRACT FROM AUTHOR]

The lungs are the second most common site of metastasis for colorectal cancer (CRC) after the liver. Rectal cancer is associated with a higher incidence of lung metastases compared to colon cancer. In China, the proportion of rectal cancer cases is around 50%, much higher than that in Western countries (nearly 30%). However, there is no available consensus or guideline focusing on CRC with lung metastases. We conducted an extensive discussion and reached a consensus of management for lung metastases in CRC based on current research reports and the experts' clinical experiences and knowledge. This consensus provided detailed approaches of diagnosis and differential diagnosis and provided general guidelines for multidisciplinary therapy (MDT) of lung metastases. We also focused on recommendations of MDT management of synchronous lung metastases and initial metachronous lung metastases. This consensus might improve clinical practice of CRC with lung metastases in China and will encourage oncologists to conduct more clinical trials to obtain high-level evidences about managing lung metastases. [ABSTRACT FROM AUTHOR]