MiRNA-145-5p inhibits gastric cancer progression via the serpin family E member 1- extracellular signal-regulated kinase-1/2 axis.

BACKGROUND: MicroRNAs (miRNAs) regulate gene expression and play a critical role in cancer physiology. However, there is still a limited understanding of the function and regulatory mechanism of miRNAs in gastric cancer (GC). AIM: To investigate the role and molecular mechanism of miRNA-145-5p (miR145-5p) in the progression of GC. METHODS: Real-time polymerase chain reaction (RT-PCR) was used to detect miRNA expression in human GC tissues and cells. The ability of cancer cells to migrate and invade was assessed using wound-healing and transwell assays, respectively. Cell proliferation was measured using cell counting kit-8 and colony formation assays, and apoptosis was evaluated using flow cytometry. Expression of the epithelial-mesenchymal transition (EMT)-associated protein was determined by Western blot. Targets of miR-145-5p were predicated using bioinformatics analysis and verified using a dual-luciferase reporter system. Serpin family E member 1 (SERPINE1) expression in GC tissues and cells was evaluated using RT-PCR and immunohistochemical staining. The correlation between SERPINE1 expression and overall patient survival was determined using Kaplan-Meier plot analysis. The association between SERPINE1 and GC progression was also tested. A rescue experiment of SERPINE1 overexpression was conducted to verify the relationship between this protein and miR-145-5p. The mechanism by which miR-145-5p influences GC progression was further explored by assessing tumor formation in nude mice. RESULTS: GC tissues and cells had reduced miR-145-5p expression and SERPINE1 was identified as a direct target of this miRNA. Overexpression of miR-145-5p was associated with decreased GC cell proliferation, invasion, migration, and EMT, and these effects were reversed by forcing SERPINE1 expression. Kaplan-Meier plot analysis revealed that patients with higher SERPINE1 expression had a shorter survival rate than those with lower SERPINE1 expression. Nude mouse tumorigenesis experiments confirmed that miR-145-5p targets SERPINE1 to regulate extracellular signal-regulated kinase-1/2 (ERK1/2). CONCLUSION: This study found that miR-145-5p inhibits tumor progression and is expressed in lower amounts in patients with GC. MiR-145-5p was found to affect GC cell proliferation, migration, and invasion by negatively regulating SERPINE1 levels and controlling the ERK1/2 pathway.

CDC45 promotes the stemness and metastasis in lung adenocarcinoma by affecting the cell cycle.

OBJECTIVE: This study aimed to assess the functions of cell division cycle protein 45 (CDC45) in Non-small cell lung cancer (NSCLC) cancer and its effects on stemness and metastasis. METHODS: Firstly, differentially expressed genes related to lung cancer metastasis and stemness were screened by differential analysis and lasso regression. Then, in vitro, experiments such as colony formation assay, scratch assay, and transwell assay were conducted to evaluate the impact of CDC45 knockdown on the proliferation and migration abilities of lung cancer cells. Western blotting was used to measure the expression levels of related proteins and investigate the regulation of CDC45 on the cell cycle. Finally, in vivo model with subcutaneous injection of lung cancer cells was performed to verify the effect of CDC45 on tumor growth. RESULTS: This study identified CDC45 as a key gene potentially influencing tumor stemness and lymph node metastasis. Knockdown of CDC45 not only suppressed the proliferation and migration abilities of lung cancer cells but also caused cell cycle arrest at the G2/M phase. Further analysis revealed a negative correlation between CDC45 and cell cycle-related proteins, stemness-related markers, and tumor mutations. Mouse experiments confirmed that CDC45 knockdown inhibited tumor growth. CONCLUSION: As a novel regulator of stemness, CDC45 plays a role in regulating lung cancer cell proliferation, migration, and cell cycle. Therefore, CDC45 may serve as a potential target for lung cancer treatment and provide a reference for further mechanistic research and therapeutic development.

S100P facilitates LUAD progression via PKA/c-Jun-mediated tumor-associated macrophage recruitment and polarization.

S100P, a member of the S100 calcium-binding protein family, is closely associated with abnormal proliferation, invasion, and metastasis of various cancers. However, its role in the lung adenocarcinoma (LUAD) tumor microenvironment (TME) remains unclear. In this study, we observed specific expression of S100P on tumor cells in LUAD patients through tissue immunofluorescence analysis. Furthermore, this expression was strongly correlated with the recruitment and polarization of tumor-associated macrophages (TAMs). Bioinformatics analysis revealed that high S100P expression is associated with poorer overall survival in LUAD patients. Subsequently, a subcutaneous mouse model demonstrated that S100P promotes recruitment and polarization of TAMs towards the M2 type. Finally, in vitro studies on LUAD cells revealed that S100P enhances the secretion of chemokines and polarizing factors by activating the PKA/c-Jun pathway, which is implicated in TAM recruitment and polarization towards the M2 phenotype. Moreover, inhibition of c-Jun expression impedes the ability of TAMs to infiltrate and polarize towards the M2 phenotype. In conclusion, our study demonstrates that S100P facilitates LUAD cells growth by recruiting M2 TAMs through PKA/c-Jun signaling, resulting in the production of various cytokines. Considering these findings, S100P holds promise as an important diagnostic marker and potential therapeutic target for LUAD.

Analysis of the Correlation Between Dynamic Characteristics and Symptoms of Gastroesophageal Reflux Disease.

OBJECTIVE: To investigate the esophageal motility characteristics of gastroesophageal reflux disease (GERD) and their relationship with symptoms. PATIENTS AND METHODS: We examined 101 patients diagnosed with GERD by endoscopy and divided them into 3 groups as follows: nonerosive reflux disease (NERD), reflux esophagitis, and Barrett esophagus. Esophageal high-resolution manometry and the GERD Questionnaire were used to investigate the characteristics of esophageal dynamics and symptoms. In addition, the reflux symptom index was completed and the patients were divided into 7 groups according to symptoms. We then determined the correlation between dynamic esophageal characteristics and clinical symptoms. RESULTS: Upper (UES) and lower (LES) esophageal sphincter pressures and the 4-second integrated relaxation pressure in the RE group were lower than those in the NERD group. The 4-second integrated relaxation pressure in the Barrett esophagus group was also lower than that in the NERD group. In the analysis of extraesophageal symptoms, high-resolution manometry showed significant differences in UES pressures among all groups. Further subgroup analysis showed that compared with the group without extraesophageal symptoms, the UES pressure of the groups with pharyngeal foreign body sensation, throat clearing, and multiple extraesophageal symptoms was lower. CONCLUSIONS: As GERD severity increases, motor dysfunction of the LES and esophageal body gradually worsens, and the LES plays an important role in GERD development. Decreased UES pressure plays an important role in the occurrence of extraesophageal symptoms, which is more noticeable in patients with pharyngeal foreign body sensation and throat clearing.

GPX8+ cancer-associated fibroblast, as a cancer-promoting factor in lung adenocarcinoma, is related to the immunosuppressive microenvironment.

BACKGROUND: Cancer-associated fibroblasts (CAFs) play a crucial role in the tumor microenvironment of lung adenocarcinoma (LUAD) and are often associated with poorer clinical outcomes. This study aimed to screen for CAF-specific genes that could serve as promising therapeutic targets for LUAD. METHODS: We established a single-cell transcriptional profile of LUAD, focusing on genetic changes in fibroblasts. Next, we identified key genes associated with fibroblasts through weighted gene co-expression network analysis (WGCNA) and univariate Cox analysis. Then, we evaluated the relationship between glutathione peroxidase 8 (GPX8) and clinical features in multiple independent LUAD cohorts. Furthermore, we analyzed immune infiltration to shed light on the relationship between GPX8 immune microenvironment remodeling. For clinical treatment, we used the tumor immune dysfunction and exclusion (TIDE) algorithm to assess the immunotherapy prediction efficiency of GPX8. After that, we screened potential therapeutic drugs for LUAD by the connectivity map (cMAP). Finally, we conducted a cell trajectory analysis of GPX8+ CAFs to show their unique function. RESULTS: Fibroblasts were found to be enriched in tumor tissues. Then we identified GPX8 as a key gene associated with CAFs through comprehensive bioinformatics analysis. Further analysis across multiple LUAD cohorts demonstrated the relationship between GPX8 and poor prognosis. Additionally, we found that GPX8 played a role in inducing the formation of an immunosuppressive microenvironment. The TIDE method indicated that patients with low GPX8 expression were more likely to be responsive to immunotherapy. Using the cMAP, we identified beta-CCP as a potential drug-related to GPX8. Finally, cell trajectory analysis provided insights into the dynamic process of GPX8+ CAFs formation. CONCLUSIONS: This study elucidates the association between GPX8+ CAFs and poor prognosis, as well as the induction of immunosuppressive formation in LUAD. These findings suggest that targeting GPX8+ CAFs could potentially serve as a therapeutic strategy for the treatment of LUAD.

Development of an invasion score based on metastasis-related pathway activity profiles for identifying invasive molecular subtypes of lung adenocarcinoma.

The invasive capacity of lung adenocarcinoma (LUAD) is an important factor influencing patients' metastatic status and survival outcomes. However, there is still a lack of suitable biomarkers to evaluate tumor invasiveness. LUAD molecular subtypes were identified by unsupervised consistent clustering of LUAD. The differences in prognosis, tumor microenvironment (TME), and mutation were assessed among different subtypes. After that, the invasion-related gene score (IRGS) was constructed by genetic differential analysis, WGCNA analysis, and LASSO analysis, then we evaluated the relationship between IRGS and invasive characteristics, TME, and prognosis. The predictive ability of the IRGS was verified by in vitro experiments. Next, the "oncoPredict" R package and CMap were used to assess the potential value of IRGS in drug therapy. The results showed that LUAD was clustered into two molecular subtypes. And the C1 subtype exhibited a worse prognosis, higher stemness enrichment activity, less immune infiltration, and higher mutation frequency. Subsequently, IRGS developed based on molecular subtypes demonstrated a strong association with malignant characteristics such as invasive features, higher stemness scores, less immune infiltration, and worse survival. In vitro experiments showed that the higher IRGS LUAD cell had a stronger invasive capacity than the lower IRGS LUAD cell. Predictive analysis based on the "oncoPredict" R package showed that the high IRGS group was more sensitive to docetaxel, erlotinib, paclitaxel, and gefitinib. Among them, in vitro experiments verified the greater killing effect of paclitaxel on high IRGS cell lines. In addition, CMap showed that purvalanol-a, angiogenesis-inhibitor, and masitinib have potential therapeutic effects in the high IRGS group. In summary we identified and analyzed the molecular subtypes associated with the invasiveness of LUAD and developed IRGS that can efficiently predict the prognosis and invasive ability of the tumor. IRGS may be able to facilitate the precision treatment of LUAD to some extent.

Mefloquine improves pulmonary fibrosis by inhibiting the KCNH2/Jak2/Stat3 signaling pathway in macrophages.

Idiopathic pulmonary fibrosis (IPF) is a life-threatening disease characterized by severe pulmonary fibrosis, for which there is an urgent need for effective therapeutic agents. Mefloquine (Mef) is a quinoline compound primarily used for the treatment of malaria. However, high doses (>25 mg/kg) may lead to side effects such as cardiotoxicity and psychiatric disorders. Here, we found that low-dose Mef (5 mg/kg) can safely and effectively treat IPF mice. Functionally, Mef can improve the pulmonary function of IPF mice (PIF, PEF, EF50, VT, MV, PENH), alleviating pulmonary inflammation and fibrosis by inhibiting macrophage activity. Mechanically, Mef probably regulates the Jak2/Stat3 signaling pathway by binding to the 492HIS site of Potassium voltage-gated channel subfamily H member 2 (KCNH2) protein in macrophages, inhibiting the secretion of macrophage inflammatory and fibrotic factors. In summary, Mef may inhibit macrophage activity by binding to KCNH2 protein, thereby slowing down the progress of IPF.

Integrating bulk-RNA sequencing and single-cell sequencing analyses to characterize adenosine-enriched tumor microenvironment landscape and develop an adenosine-related prognostic signature predicting immunotherapy in lung adenocarcinoma.

The adenosine-signaling axis has been recognized as an important immunomodulatory pathway in tumor immunity. However, the biological role of the adenosine-signaling axis in the remodeling of the tumor microenvironment (TME) in lung adenocarcinoma (LUAD) remains unclear. Here, we quantified adenosine signaling (ado_sig) in LUAD samples using the GSVA method and assessed the prognostic value of adenosine in LUAD. Afterward, we explored the heterogeneity of the tumor-immune microenvironment at different adenosine levels. In addition, we analyzed the potential biological pathways engaged by adenosine. Next, we established single-cell transcriptional profiles of LUAD and analyzed cellular composition and cell-cell communication analysis under different adenosine microenvironments. Moreover, we established adenosine-related prognostic signatures (ARS) based on comprehensive bioinformatics analysis and evaluated the efficacy of ARS in predicting immunotherapy. The results demonstrated that adenosine signaling adversely impacted the survival of immune-enriched LUAD. The high-adenosine microenvironment exhibited elevated pro-tumor-immune infiltration, including M2 macrophages and displayed notably increased epithelial-mesenchymal transition (EMT) transformation. Furthermore, adenosine signaling displayed significant associations with the expression patterns and prognostic value of immunomodulators within the TME. Single-cell sequencing data revealed increased fibroblast occupancy and a prominent activation of the SPP1 signaling pathway in the high adenosine-signaling microenvironment. The ARS exhibited promising effectiveness in prognostication and predicting immunotherapy response in LUAD. In summary, overexpression of adenosine can cause a worsened prognosis in the LUAD with abundant immune infiltration. Moreover, increased adenosine levels are associated with pro-tumor-immune infiltration, active EMT transformation, pro-tumor angiogenesis, and other factors promoting cancer progression, which collectively contribute to the formation of an immunosuppressive microenvironment. Importantly, the ARS developed in this study demonstrate high efficacy in evaluating the response to immunotherapy.

RACGAP1 promotes the progression and poor prognosis of lung adenocarcinoma through its effects on the cell cycle and tumor stemness.

OBJECTION: Investigating the key genes and mechanisms that influence stemness in lung adenocarcinoma. METHODS: First, consistent clustering analysis was performed on lung adenocarcinoma patients using stemness scoring to classify them. Subsequently, WGCNA was utilized to identify key modules and hub genes. Then, machine learning methods were employed to screen and identify the key genes within these modules. Lastly, functional analysis of the key genes was conducted through cell scratch assays, colony formation assays, transwell migration assays, flow cytometry cell cycle analysis, and xenograft tumor models. RESULTS: First, two groups of patients with different stemness scores were obtained, where the high stemness score group exhibited poor prognosis and immunotherapy efficacy. Next, LASSO regression analysis and random forest regression were employed to identify genes (PBK, RACGAP1) associated with high stemness scores. RACGAP1 was significantly upregulated in the high stemness score group of lung adenocarcinoma and closely correlated with clinical pathological features, poor overall survival (OS), recurrence-free survival (RFS), and unfavorable prognosis in lung adenocarcinoma patients. Knockdown of RACGAP1 suppressed the migration, proliferation, and tumor growth of cancer cells. CONCLUSION: RACGAP1 not only indicates poor prognosis and limited immunotherapy benefits but also serves as a potential targeted biomarker influencing tumor stemness.

SPOCK1, as a potential prognostic and therapeutic biomarker for lung adenocarcinoma, is associated with epithelial-mesenchymal transition and immune evasion.

BACKGROUND: The occurrence of epithelial-mesenchymal transition (EMT) and immune evasion is considered to contribute to poor prognosis in lung adenocarcinoma (LUAD). Therefore, this study aims to explore the key oncogenes that promote EMT and immune evasion and reveal the expression patterns, prognostic value, and potential biological functions. METHODS: Firstly, we identified gene modules associated with EMT and Tumor Immune Dysfunction and Exclusion (TIDE) through weighted gene co-expression network analysis (WGCNA). Next, we utilized differential analysis and machine learning to identify the key genes and validate them. Moreover, we analyzed the correlation between key genes and tumor microenvironment remodeling, drug sensitivity, as well as mutation frequency. Furthermore, we explored and validated their malignant biological characteristics through in vitro experiments and clinical samples. Finally, potential drugs for LUAD were screened based on CMap and validated through experiments. RESULTS: Firstly, WGCNA analysis revealed that red and green modules were highly correlated with EMT and TIDE. Among them, upregulated expression of SPOCK1 was observed in lung adenocarcinoma tissues and was associated with poor prognosis. Additionally, patients in the high SPOCK1 group showed more activation of malignant oncogenic pathways, higher infiltration of immunosuppressive components, and a higher frequency of mutations. The knockdown of SPOCK1 suppressed invasion and metastasis capabilities of lung adenocarcinoma cells, and the high expression of SPOCK1 was associated with low infiltration of CD8+ T cells. Therapeutic aspects, SPOCK1 can be a candidate indicator for drug sensitivity and CMap showed that VER-155008 was the drug candidate with the largest perturbation effect on the SPOCK1 expression profile. In vitro and in vivo experiments validated the cancer-inhibitory effect of VER-155008 in LUAD. CONCLUSION: This study revealed through comprehensive bioinformatics analysis and experimental analysis that SPOCK1 can promote EMT and immune escape in LUAD, and it may serve as a promising candidate prognostic biomarker and therapeutic target for LUAD.

CD4 levels and NSCLC metastasis: the benefits of maintaining moderate levels.

OBJECTIVES: Prior researches indicate that peripheral blood CD4 levels have an inverse correlation with distant tumor metastasis in non-small cell lung cancer (NSCLC). However, the linear relationship between CD4 and distant metastasis lacks clarity. Hence, the objective of this study was to ascertain the linear relationship between CD4 and distant metastasis in NSCLC patients. METHODS: This retrospective study analyzed clinical and laboratory data of NSCLC patients between March 2016 and July 2022 at the Cancer Hospital of Anhui University of Technology. The study first applied a generalized summation model and smoothing curve fitting to determine if there was a linear relationship between CD4 and NSCLC metastasis. Secondarily, univariate logistic analysis and multiple linear regression were used to analyze the odds ratio (OR) of CD4 as a continuous variable, dichotomous variable, and trichotomous variable when predicting NSCLC metastasis. In addition, stratified and subgroup analyses were conducted to assess the reliability of CD4 in different NSCLC patient populations. RESULTS: The study included a total of 213 NSCLC patients, among which 122 had distant metastasis and 91 had no metastasis. The smoothing curve fitting analysis revealed a U-shaped relationship between CD4 and NSCLC metastasis with a threshold effect. The univariate logistic analysis indicated that continuous CD4 expression was not significantly associated with NSCLC metastasis (P = 0.051); however, high levels of CD4 expression (≥ 35.06%) were found to be a protective factor against NSCLC metastasis when CD4+ T was a dichotomous variable (OR = 0.49, P = 0.010). Furthermore, multivariate linear regression models showed that low (< 32%) or high levels (> 44%) of CD4 significantly increased the risk of NSCLC metastasis compared to medium levels (32-44%) when CD4+ T was trichotomized. The significance was maintained in stratified analysis in relation to age, sex, type of pathology, smoke, PS, and T stage. CD4 levels were U-shaped in relation to different sites of distant metastases (bone, brain, liver), but not with lung metastases. CONCLUSIONS: A threshold effect is shown to exist between the peripheral blood CD4 and distant metastasis in NSCLC patients. It was revealed that the risk of distant metastasis is lower when CD4 is maintained between 32 and 44%, whereas low (< 32%) or high (> 44) levels of CD4 are associated with an increased risk of distant metastasis in NSCLC patients.

A2aR on lung adenocarcinoma cells: A novel target for cancer therapy via recruiting and regulating tumor-associated macrophages.

Adenosine 2a receptor (A2aR), a typical GPCR with a high affinity for adenosine, is widely expressed on immune cells, inhibiting anti-tumor immune response accordingly. Here, we identify that A2aR is specifically expressed on tumor cells from lung adenocarcinoma (LUAD) patients, closely related to their prognosis and positively correlated with tumor-associated macrophages (TAMs) infiltration. We hypothesize that blocking A2aR on LUAD cells will inhibit the role of TAMs and control tumor growth. Constructing models of TAMs and LUAD mice, we find that A2aR highly expressed on LUAD cells promotes the secretion of chemokines and polarizing factors through activating PI3K/AKT/NF-κB pathway, thereby promoting the migration and invasion of TAMs. Functionally, blocking A2aR significantly suppresses TAMs infiltration and attenuates tumor burden in LUAD mice. Notably, the M2 polarization of TAMs can also be prevented by inhibiting A2aR in vitro. Together, our studies demonstrate that A2aR on LUAD cells drives TAMs migration and polarization, and blockade of A2aR may support a novel and potent therapeutic option for LUAD.

An immune indicator based on BTK and DPEP2 identifies hot and cold tumors and clinical treatment outcomes in lung adenocarcinoma.

In lung adenocarcinoma (LUAD), immune heterogeneity of hot and cold tumors has been recognized as one of the major factors affecting immunotherapy and other common treatments. However, there is still a lack of biomarkers that can effectively identify the immunophenotype of cold and hot tumors. First, the immune signatures were obtained based on literature mining, including macrophage/monocyte, IFN-γ response, TGF-ß response, IL12 response, lymphocyte activation, and ECM/Dve/immune response. Subsequently, LUAD patients were further clustered into different immune phenotypes based on these immune signatures. Next, the key genes related to the immune phenotypes were screened by WGCNA analysis, univariate analysis, and lasso-cox analysis, and the risk signature was established via the key genes. In additional, we compared the clinicopathological characteristics, drug sensitivity, the abundance of immune infiltration, and the efficacy of immunotherapy and commonly used therapies between patients in the high- and low-risk groups in LUAD. LUAD patients were divided into immune hot phenotype and immune cold phenotype groups. The clinical presentation showed that patients with the immune hot phenotype had higher immunoactivity (including higher MHC, CYT, immune, stromal, ESTIMATE scores, higher abundance of immune cell infiltration, higher abundance of TIL, and enrichment of immune-enriched subtypes) and better survival outcomes than those with the immune cold phenotype. Subsequently, WGCNA analysis, univariate analysis, and lasso-cox analysis identified the genes highly associated with the immune phenotype: BTK and DPEP2. The risk signature, consisting of BTK and DPEP2, is highly correlated with the immune phenotype. High-risk scores were enriched in patients with immune cold phenotype and low-risk scores were enriched in patients with immune hot phenotype. Compared to the high-risk group, the low-risk group had better clinical performance, higher drug sensitivity, and a higher degree of immunoactivity, as well as better efficacy in receiving immunotherapy and common adjuvant therapy. This study developed an immune indicator consisting of BTK and DPEP2 based on the heterogeneity of hot and cold Immunophenotypes of the tumor microenvironment. This indicator has good efficacy in predicting prognosis and assessing the efficacy of immunotherapy, chemotherapy, and radiotherapy. It has the potential to facilitate personalized and precise treatment of LUAD in the future.

LncRNA PTOV1-AS2 Promotes Colon Cancer Progression through the miR-145-5p/FSCN1 Axis.

Objective: The long noncoding RNA (lncRNA) gene PTOV1-AS2 is a potentially oncogenic lncRNA gene. However, its role and regulatory mechanism in the occurrence and development of colon cancer are still unclear. In this study, the lncRNA PTOV1-AS2 was used as a starting point to investigate the role of competing endogenous RNA (ceRNA) regulatory mechanisms in colon cancer. Methods: The expression of lncRNA PTOV1-AS2 mRNA in colon cancer tissues and cell lines was measured by quantitative real-time polymerase chain reaction (qRT-PCR) and screened for differential expression in cells. We examined the effects of lncRNA PTOV1-AS2 overexpression or downregulation of its expression on various cellular processes in HCT116 and SW620 cells after the transfection with an overexpression construct or PTOV1-AS2p-specific shRNA, respectively. In particular, we examined the effects on cell proliferation, migration, and invasion using the cell counting kit-8 CCK-8 assay and Transwell migration and invasion assays, respectively. In addition, the binding targets of lncRNA PTOV1-AS2/miR-145-5p and miR-145-5p/FSCN1 were predicted using various bioinformatics tools and validated by a dual luciferase assay. We also examined the effect of the lncRNA PTOV1-AS2/miR-145-5p axis on FSCN1 expression by qRT-PCR analysis. Furthermore, we investigated the effect of the PTOV1-AS2/miR-145-5p/FSCN1 axis on the biological function of colon cancer cells using an in vitro colon cancer cell model with reduced expression of PTOV1-AS2 and simultaneous transfection of a miR-145-5p inhibitor or FSCN1 vector. Additionally, we established a colon cancer xenograft tumor nude mouse model and used it to investigate the effect of locally injected lncRNA PTOV1-AS2 vector on the tumor growth and survival status of tumor-bearing mice. Results: We found that PTOV1-AS2 was highly expressed in colon cancer, which was associated with worse survival. High expression of PTOV1-AS2 promoted cell proliferation, migration, and invasion, while low expression of PTOV1-AS2 inhibited these processes in HCT116 and SW620 cells. The microRNA miR-145-5p was found to bind to the 3'-UTR region of both PTOV1-AS2 and FSCN1. In addition, miR-145-5p decreased the protein expression of its target gene FSCN1 and reduced the PTOV1-AS2-induced expression of FSCN1 in colon cancer cell lines. Also, silencing miR-145-5p or enhancing FSCN1 expression could partially restore the inhibition of cell proliferation, migration, invasion, and the tumorigenic capacity caused by silencing the expression of PTOV1-AS2 in vitro and in vivo. Conclusion: PTOV1-AS2 promotes colon cancer progression by "sponging" miR-145-5p to upregulate FSCN1.

Construction and Validation of a Novel Immune-Related Gene Pairs-Based Prognostic Model in Lung Adenocarcinoma.

OBJECT: Focus on immune-related gene pairs (IRGPs) and develop a prognostic model to predict the prognosis of patients with lung adenocarcinoma (LUAD). METHODS: First, the LUAD patient dataset was downloaded from The Cancer Genome Atlas database, and paired analysis of immune-related genes was subsequently conducted. Then, LASSO regression was used to screen prognostic IRGPs for building a risk prediction model. Meanwhile, the Gene Expression Omnibus database was used for external validation of the model. Next, the clinical predictive power of IRGPs features was assessed by uni-multivariate Cox regression analysis, the infiltration of key immune cells in high and low IRGPs risk groups was analyzed with CIBERSORT, quanTIseq, and Timer, and the key pathways enriched for IRGPs were assessed using the Kyoto Encyclopedia of Genes and Genomes. Finally, the expression and related functions of key immune cells and genes were verified by immunofluorescence and cell experiments of tissue samples. RESULTS: It was revealed that the risk score of 19 IRGPs could be used as accurate indicators to evaluate the prognosis of LUAD patients, and the risk score was mainly related to T cell infiltration based on CIBERSORT analysis. Two genes of IRGPs, IL6, and CCL2, were found to be closely associated with the expression of PD-1/PD-L1 and the function of T-cells. Depending on the results of tissue immunofluorescence, IL6, CCL2, and T cells were highly expressed in the LUAD tissues of patients. Furthermore, IL6 and CCL2 were positively correlated with the expression of T cells. Besides, qRT-PCR assay in four different LUAD cells proved that IL6 and CCL2 were positively correlated with the expression of PD-L1 (P < .001). CONCLUSIONS: Based on 19 IRGPs, an effective prognosis model was established to predict the prognosis of LUAD patients. In addition, IL6 and CCL2 are closely related to the function of T-cells.

Efficacy and Safety of Drug-Eluting Beads Bronchial Arterial Chemoembolization in Treating Patients with Lung Cancer Who Were Complicated with Hemoptysis.

Background: This study explored the effectiveness and safety of drug-eluting beads bronchial arterial chemoembolization (DEB-BACE) in patients with lung cancer who were complicated with hemoptysis. Materials and Methods: In total, 11 patients with lung cancer who were complicated with hemoptysis and underwent DEB-BACE treatment were analyzed. Clinical success was defined as no hemoptysis or reduction of hemoptysis volume >50% after treatment. Hemoptysis recurrence was recorded, and overall survival (OS) was calculated. Results: After DEB-BACE treatment, the clinical and technical success was 100%: in detail, 10 (90.0%) patients presented with no hemoptysis and 1 (9.1%) patient exhibited a reduction of hemoptysis volume >50%. Regarding the prognosis, 1 (9.1%) patient had hemoptysis recurrence at 46 d after DEB-BACE treatment. Furthermore, 4 (36.4%) patients died (1 [9.1%] patient died of nonhemoptysis asphyxia; 1 [9.1%] patient died of massive gastrointestinal hemorrhage; 1 [9.1%] patient died of respiratory failure; and 1 [9.1%] patient died of hemoptysis recurrence). Additionally, the mean OS in total patients was 14.2 (95% confidence interval: 8.2-20.3) months. As to adverse events, 1 (9.1%) patient showed high fever, 2 (18.2%) patients exhibited low fever, and 1 (9.1%) patient suffered from chest pain. Conclusions: DEB-BACE can be considered an effective and safe treatment in treating hemoptysis in patients with lung cancer.

Identification of a ferroptosis-related gene signature for prognosis prediction in colorectal cancer patients and relationship with vitamin D.

Ferroptosis is a promising colorectal cancer (CRC) treatment strategy; however, its value in prognosis remains at an exploratory stage. Little research has been conducted on vitamin D and ferroptosis, although vitamin D has been shown to inhibit CRC through various mechanisms. A retrospective study was conducted using RNA-seq profiles and corresponding clinical information of CRC patients retrieved from TCGA and GEO databases.We used R package to process and analyze the data. We established the prognostic signature with elastic network regression model. KEGG was used to analyze pathways related to FRGs, and protein-protein interaction(PPI)was used to identify potential interactions with vitamin D. In HCT116 cells, the levels of cysteine (Cys), glutathione (GSH), and reactive oxygen species (ROS) and the expression of ferroptosis marker genes were measured by Western blot and qRT-PCR. Results showed, a prognostic signature containing 39 FRGs was established, and the Area Under Curve (AUC) of the 2nd, 5th, and 8th years were 0.81, 0.81, and 0.78, respectively. There were distinct differences in survival probability between the high- and low-risk groups, and the signature was applicable to stratified survival analysis based on tumor stage. The risk score possessed an independent prognostic value. Importantly, we found that vitamin D receptor (VDR) has a potential relationship with many FRGs, and vitamin D promotes ferroptosis in CRC cells and affects the expression of TP53, MAPK3, and SLC7A11. In summary, a signature with FRGs can effectively predict the prognosis of CRC. Vitamin D can promote ferroptosis in CRC.

Surgical Treatment is Still Recommended for Patients Over 75 Years with IA NSCLC: A Predictive Model Based on Surveillance, Epidemiology and End Results Database.

BACKGROUND: To determine the populations who suitable for surgical treatment in elderly patients (age ≥ 75 y) with IA stage. METHODS: The clinical data of NSCLC patients diagnosed from 2010 to 2015 were collected from the SEER database and divided into surgery group (SG) and no-surgery groups (NSG). The confounders were balanced and differences in survival were compared between groups using PSM (Propensity score matching, PSM). Cox regression analysis was used to screen the independent factors that affect the Cancer-specific survival (CSS). The surgery group was defined as the patients who surgery-benefit and surgery-no benefit according to the median CSS of the no-surgery group, and then randomly divided into training and validation groups. A surgical benefit prediction model was constructed in the training and validation group. Finally, the model is evaluated using a variety of methods. RESULTS: A total of 7297 patients were included. Before PSM (SG: n = 3630; NSG: n = 3665) and after PSM (SG: n = 1725, NSG: n = 1725) confirmed that the CSS of the surgery group was longer than the no-surgery group (before PSM: 82 vs. 31 months, P < .0001; after PSM: 55 vs. 39 months, P < .0001). Independent prognostic factors included age, gender, race, marrital, tumor grade, histology, and surgery. In the surgery cohort after PSM, 1005 patients (58.27%) who survived for more than 39 months were defined as surgery beneficiaries, and the 720 patients (41.73%) were defined surgery-no beneficiaries. The surgery group was divided into training group 1207 (70%) and validation group 518 (30%). Independent prognostic factors were used to construct a prediction model. In training group (AUC = .678) and validation group (AUC = .622). Calibration curve and decision curve prove that the model has better performance. CONCLUSIONS: This predictive model can well identify elderly patients with stage IA NSCLC who would benefit from surgery, thus providing a basis for clinical treatment decisions.

Relationship between lymphocyte to monocyte ratio and brain metastasis in non-smalll cell lung cancer patients.

OBJECTIVE: To observe whether there is an association between the lymphocyte/monocyte ratio (LMR) and the occurrence of brain metastases in non-small cell lung cancer (BM-NSCLC) patients. METHOD: Retrospective collection of patients' information meeting the standards of nano-excretion, was done from January 2016 to September 2021. We calculated the odds ratio (OR) and 95% confidence interval (CI) of LMR versus BM-NSCLC using multivariate logistic regression, and stratified analysis was performed. The linear or nonlinear relationships that exist between the two were explored by generalized additive model and smoothed curve fitting. RESULTS: In all three models, LMR was negatively associated with BM-NSCLC (Model 1: OR, 0.72; 95% CI, 0.57-0.9; P=0.0037. Model 2: OR, 0.64; 95% CI, 0.50-0.82; P=0.0005. Model 3: OR, 0.62; 95% CI, 0.47-0.81; P=0.0005). This negative association was shown to be significant in patients with adenocarcinoma (ADC), who were, female, and in T2-T4 stages, and N1-N3 stages (ADC: OR, 0.59; 95% CI, 0.44-0.80; P=0.0006. female: OR, 0.37; 95% CI, 0.20-0.68; P=0.0013. T2-T4: OR, 0.59; 95% CI, 0.43-0.82; P=0.0014; N1-N3: OR, 0.62; 95% CI, 0.45-0.86; P=0.0042), according to subgroup analysis. CONCLUSION: After controlling for relevant confounders, this study demonstrated that increased LMR levels in NSCLC patients were substantially and inversely connected to their likelihood of BM, particularly in patients with ADC, who were female, or had T2-T4, and N1-N3 stages.