Prognosis In Lung Squamous Cell Carcinoma Research Articles

The Comprehensive Characterization of B7-H3 Expression in the Tumor Microenvironment of Lung Squamous Cell Carcinoma: A Retrospective Study.

Lung squamous cell carcinoma (LSCC) is refractory to various therapies for non-small cell cancer; therefore, new therapeutic approaches are required to improve the prognosis of LSCC. Although immunotherapies targeting B7 family molecules were explored as treatments for several cancer types, the expression and significance of B7-H3 in the tumor microenvironment (TME) and its relationship with other immune checkpoint molecules have not yet been investigated in detail. We used high-throughput quantitative multiplex immunohistochemistry to examine B7-H3 expression in the TME. We investigated the relationship between B7-H3 expression and prognosis as well as changes in the TME with B7-H3 expression using 110 surgically resected pathological specimens retrospectively. We examined the correlation between B7-H3 and programmed cell death-ligand 1 (PD-L1) expression in single cells. High B7-H3 expression in tumor cells was associated with a better prognosis and a significant increase in the number of CD163+PD-L1+ macrophages. Quantitative analysis revealed that there is a positive correlation between B7-H3 and PD-L1 expression in tumor and stromal cells, as well as in intratumoral tumor-infiltrating lymphocytes and tumor-associated macrophages in the same cells. CD68+, CD163+, and CK+ cells with PD-L1+ phenotypes had higher B7-H3 expression compared to PD-L1- cells. Our findings demonstrate a correlation between B7-H3 and PD-L1 expression in the same cells, indicating that therapies targeting B7-H3 could provide additional efficacy in patients refractory to PD-L1-targeting therapies.

THY1 is a prognostic-related biomarker via mediating immune infiltration in lung squamous cell carcinoma (LUSC).

Thymus cell antigen 1 (THY1) has been proven to play pivotal roles in many diseases. However, we do not fully understand its functional mechanism, especially in lung squamous cell carcinoma (LUSC). Here, we aimed to perform a comprehensive analysis to explore the expression and prognostic values of THY1 in LUSC using bioinformatic technology. Some online public databases (e.g., ONCOMINE, PrognoScan, TIMER, Kaplan-Meier plotter, STRING, LinkedOmics, and GEPIA) were used to explore the expression, prognostic significance, and potential molecular mechanism of THY1. The analysis indicated that THY1 was significantly up-regulated and closely correlated with poor prognosis in many malignant tumors, including LUSC. Further analysis revealed that over-expression of THY1 was significantly correlated with clinicopathological parameters (e.g., individual cancer stage, age, smoking habits, nodal metastasis status, and TP53 mutation status) in LUSC. The CpG islands methylation of THY1 was negatively correlated with THY1 mRNA expression in The Cancer Genome Atlas Program (TCGA). Further enrichment analysis of THY1 correlated genes revealed that they were mainly correlated with the formation of extracellular matrix (ECM), and got involved in the pathway of epithelial mesenchymal transition (EMT). Furthermore, differentially expressed THY1 was significantly correlated with immune cell infiltrations and poor prognosis in LUSC. In summary, bioinformatic analysis demonstrated that THY1 was significantly over-expressed and closely correlated with unfavorable prognosis in LUSC, which may apply as a promising diagnostic and therapeutic biomarker for LUSC in the future.

Different types of tumor microvessels in stage I-IIIA squamous cell lung cancer and their clinical significance.

Lung cancer (LC) is the leading cause of morbidity and mortality among malignant neoplasms. Improving the diagnosis and treatment of LC remains an urgent task of modern oncology. Previously, we established that in gastric, breast and cervical cancer, tumor microvessels (MVs) differ in morphology and have different prognostic significance. The connection between different types of tumor MVs and the progression of LC is not well understood. To evaluate the morphological features and clinical significance of tumor MVs in lung squamous cell carcinoma (LUSC). A single-center retrospective cohort study examined medical records and archival paraffin blocks of 62 and 180 patients with stage I-IIIA LUSC in the training and main cohorts, respectively. All patients underwent radical surgery (R0) at the Orenburg Regional Cancer Clinic from May/20/2009 to December/14/2021. Tumor sections were routinely processed, and routine Mayer's hematoxylin and eosin staining and immunohistochemical staining for cluster of differentiation 34 (CD34), podoplanin, Snail and hypoxia-inducible factor-1 alpha were performed. The morphological features of different types of tumor MVs, tumor parenchyma and stroma were studied according to clinicopathological characteristics and LUSC prognosis. Statistical analysis was performed using Statistica 10.0 software. Univariate and multivariate logistic regression analyses were performed to identify potential risk factors for LUSC metastasis to regional lymph nodes (RLNs) and disease recurrence. Receiver operating characteristic curves were constructed to discriminate between patients with and without metastases in RLNs and those with and without disease recurrence. The effectiveness of the predictive models was assessed by the area under the curve. Survival was analyzed using the Kaplan-Meier method. The log-rank test was used to compare survival curves between patient subgroups. A value of P < 0.05 was considered to indicate statistical significance. Depending on the morphology, we classified tumor vessels into the following types: normal MVs, dilated capillaries (DCs), atypical DCs, DCs with weak expression of CD34, "contact-type" DCs, structures with partial endothelial linings, capillaries in the tumor solid component and lymphatic vessels in lymphoid and polymorphocellular infiltrates. We also evaluated the presence of loose, fine fibrous connective tissue (LFFCT) and retraction clefts in the tumor stroma, tumor spread into the alveolar air spaces (AASs) and fragmentation of the tumor solid component. According to multivariate analysis, the independent predictors of LUSC metastasis in RLNs were central tumor location (P < 0.00001), the presence of retraction clefts (P = 0.003), capillaries in the tumor solid component (P = 0.023) and fragmentation in the tumor solid component (P = 0.009), whereas the independent predictors of LUSC recurrence were tumor grade 3 (G3) (P = 0.001), stage N2 (P = 0.016), the presence of LFFCT in the tumor stroma (P < 0.00001), fragmentation of the tumor solid component (P = 0.0001), and the absence of tumor spread through the AASs (P = 0.0083). The results obtained confirm the correctness of our previously proposed classification of different types of tumor vessels and may contribute to improving the diagnosis and treatment of LUSC.

Significance of NKX2-1 as a biomarker for clinical prognosis, immune infiltration, and drug therapy in lung squamous cell carcinoma.

This study was performed to determine the biological processes in which NKX2-1 is involved and thus its role in the development of lung squamous cell carcinoma (LUSC) toward improving the prognosis and treatment of LUSC. Raw RNA sequencing (RNA-seq) data of LUSC from The Cancer Genome Atlas (TCGA) were used in bioinformatics analysis to characterize NKX2-1 expression levels in tumor and normal tissues. Survival analysis of Kaplan-Meier curve, the time-dependent receiver operating characteristic (ROC) curve, and a nomogram were used to analyze the prognosis value of NKX2-1 for LUSC in terms of overall survival (OS) and progression-free survival (PFS). Then, differentially expressed genes (DEGs) were identified, and Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and Gene Set Enrichment Analysis (GSEA) were used to clarify the biological mechanisms potentially involved in the development of LUSC. Moreover, the correlation between the NKX2-1 expression level and tumor mutation burden (TMB), tumor microenvironment (TME), and immune cell infiltration revealed that NKX2-1 participates in the development of LUSC. Finally, we studied the effects of NKX2-1 on drug therapy. To validate the protein and gene expression levels of NKX2-1 in LUSC, we employed immunohistochemistry(IHC) datasets, The Gene Expression Omnibus (GEO) database, and qRT-PCR analysis. NKX2-1 expression levels were significantly lower in LUSC than in normal lung tissue. It significantly differed in gender, stage and N classification. The survival analysis revealed that high expression of NKX2-1 had shorter OS and PFS in LUSC. The multivariate Cox regression hazard model showed the NKX2-1 expression as an independent prognostic factor. Then, the nomogram predicted LUSC prognosis. There are 51 upregulated DEGs and 49 downregulated DEGs in the NKX2-1 high-level groups. GO, KEGG and GSEA analysis revealed that DEGs were enriched in cell cycle and DNA replication.The TME results show that NKX2-1 expression was positively associated with mast cells resting, neutrophils, monocytes, T cells CD4 memory resting, and M2 macrophages but negatively associated with M1 macrophages. The TMB correlated negatively with NKX2-1 expression. The pharmacotherapy had great sensitivity in the NKX2-1 low-level group, the immunotherapy is no significant difference in the NKX2-1 low-level and high-level groups. The analysis of GEO data demonstrated concurrence with TCGA results. IHC revealed NKX2-1 protein expression in tumor tissues of both LUAD and LUSC. Meanwhile qRT-PCR analysis indicated a significantly lower NKX2-1 expression level in LUSC compared to LUAD. These qRT-PCR findings were consistent with co-expression analysis of NKX2-1. We conclude that NKX2-1 is a potential biomarker for prognosis and treatment LUSC. A new insights of NKX2-1 in LUSC is still needed further research.

Diagnostic Value of GDF10 for the Tumorigenesis and Immune Infiltration in Lung Squamous Cell Carcinoma.

Lung squamous cell carcinoma (LUSC) is associated with a low survival rate. Evidence suggests that bone morphogenetic proteins (BMPs) and their receptors (BMPRs) play crucial roles in tumorigenesis and progression. However, a comprehensive analysis of their role in LUSC is lacking. Our study aimed to explore the relationship between BMPs/BMPRs expression levels and the tumorigenesis and prognosis of LUSC. The "R/Limma" package was utilized to analyze the differential expression characteristics of BMPs/BMPRs in LUSC, using data from TCGA, GTEx, and GEO databases. Concurrently, the "survminer" packages were employed to investigate their prognostic value and correlation with clinical features in LUSC. The core gene associated with LUSC progression was further explored through weighted gene correlation network analysis (WGCNA). LASSO analysis was conducted to construct a prognostic risk model for LUSC. Clinical specimens were examined by immunohistochemical analysis to confirm the diagnostic value in LUSC. Furthermore, based on the tumor immune estimation resource database and tumor-immune system interaction database, the role of the core gene in the tumor microenvironment of LUSC was explored. GDF10 had a significant correlation only with the pathological T stage of LUSC, and the protein expression level of GDF10 decreased with the tumorigenesis of LUSC. A prognostic risk model was constructed with GDF10 as the core gene and 5 hub genes (HRASLS, HIST1H2BH, FLRT3, CHEK2, and ALPL) for LUSC. GDF10 showed a significant positive correlation with immune cell infiltration and immune checkpoint expression. GDF10 might serve as a diagnostic biomarker reflecting the tumorigenesis of LUSC and regulating the tumor immune microenvironment to guide more effective treatment for LUSC.

Tumor microenvironment characteristics and prognostic role of m6A modification in lung squamous cell carcinoma

BackgroundIt has recently been determined that N6-methyladenosine (m6A) RNA methylation regulators have prominent effects on several cancers. However, the potential role of m6A modification in lung squamous cell carcinoma (LUSC) remains unclear. MethodsWe evaluated the modification pattern of m6A and studied the biological function of m6A regulators in LUSC. Then, we constructed the m6Ascore to predict the prognosis of LUSC and analyzed the relationship between the m6Ascore and tumor mutation burden, immune cell infiltration, and immunotherapy. ResultIn the unsupervised consensus cluster analysis, three different m6Aclusters were identified, which correspond to an immune activation state, a moderate immune activation state, and an immune tolerance state. Forty-two genes related to the m6A phenotype were used to construct the m6Ascore; subsequently, multiple validations of the m6Ascore were carried out to determine the relationship between the score and immune cell infiltration and response to CTLA-4/PD-1 inhibitor treatment. Further analysis revealed that the m6Ascore could effectively predict the prognosis of LUSC and that the m6A phenotype-related genes, FAM162A and LOM4, might be potential biomarkers. ConclusionThese findings highlight the potential role of m6A modification in the prognosis, TME, and immunotherapy of LUSC and have profound implications for developing more effective personalized treatment strategies for LUSC.

A novel gene signature related to focal adhesions for distinguishing and predicting the prognosis of lung squamous cell carcinoma.

Lung squamous cell carcinoma (LUSC) is a devastating and difficult-to-treat type of lung cancer, and the prognosis of LUSC is the worst. The functional roles of focal adhesion-related genes were explored in LUSC based on data from The Cancer Genome Atlas (TCGA). RNA sequencing data and clinical characteristics of LUSC patients in TCGA-LUSC were obtained from the TCGA database. Through systematic analysis, we screened the prognostic genes and determined the focal adhesion-related pathways closely associated with LUSC. We identified 444 prognostic genes and focal adhesion-related pathways intimately associated with LUSC. According to the focal adhesion-related genes, TCGA-LUSC patients were well divided into two groups: the low-risk group (G1) and the high-risk group (G2). A differential expression analysis identified 44 differentially expressed genes (DEGs) upregulated in the low-risk G1 group and 379 DEGs upregulated in the high-risk G2 group. The upregulated DEGs in the G1 group were primarily related to tyrosine metabolism, steroid hormone biosynthesis, retinol metabolism, platinum drug resistance, pentose and glucuronate interconversions, and metabolism of xenobiotics by cytochrome P450, while the downregulated DEGs in the G1 group were primarily related to ECM-receptor interaction, focal adhesion, proteoglycans in cancer, small cell lung cancer, cytokine-cytokine receptor interaction, and TGF-beta signaling pathway. The immune activity of the G1 group was lower than that of the G2 group, and the half-maximal inhibitory concentration (IC50) of five chemotherapy drugs (i.e., gemcitabine, methotrexate, vinorelbine, paclitaxel, and cisplatin) was significantly different between the G1 and G2 groups. Furthermore, a 10-gene prognostic model was constructed to predict the prognosis for LUSC patients: ITGA3, VAV2, FLNC, FLT4, HGF, MYL2, ITGB1, PDGFRA, CCND2, and PPP1CB. The status of focal adhesion-related genes has a close relationship with tumor classification and immunity in LUSC patients. A novel focal adhesion-related signature had good prognostic and predictive performance for LUSC. Our findings may provide new insight into the diagnosis and treatment of LUSC.

Prediction of Prognostic Features Based on Neutrophil-Related Genes for Lung Squamous Cell Carcinoma Reveals Immune Landscape and Drug Candidates.

Background: Since to the prognosis of lung squamous cell carcinoma is generally poor, there is an urgent need to innovate new prognostic biomarkers and therapeutic targets to improve patient outcomes. Objectives: Our goal was to develop a novel multi-gene prognostic model linked to neutrophils for predicting lung squamous cell carcinoma prognosis. Methods: We utilized messenger RNA expression profiles and relevant clinical data of lung squamous cell carcinoma patients from the Cancer Genome Atlas database. Through K-means clustering, least absolute shrinkage and selection operator regression, and univariate/multivariate Cox regression analyses, we identified 12 neutrophil-related genes strongly related to patient survival and constructed a prognostic model. We verified the stability of the model in the Cancer Genome Atlas database and gene expression omnibus validation set, demonstrating the robust predictive performance of the model. Results: Immunoinfiltration analysis revealed remarkably elevated levels of infiltration for natural killer cells resting and monocytes in the high-risk group compared to the low-risk group, while macrophages had considerably lower infiltration in the high risk group. Most immune checkpoint genes, including programmed cell death protein 1 and cytotoxic T-lymphocyte-associated antigen 4, exhibited high expression levels in the high risk group. Tumor immune dysfunction and exclusion scores and immunophenoscore results suggested a potential inclination toward immunotherapy in the "RIC" version V2 revised high risk group. Moreover, prediction results from the CellMiner database revealed great correlations between drug sensitivity (e.g., Vinorelbine and PKI-587) and prognostic genes. Conclusion: Overall, our study established a reliable prognostic risk model that possessed significant value in predicting the overall survival of lung squamous cell carcinoma patients and may guide personalized treatment strategies. (Rev Invest Clin. 2024;76(2):116-31).

Identification of tumor-suppressor genes in lung squamous cell carcinoma through integrated bioinformatics analyses.

Lung cancer is a prevalent malignancy, and fatalities of the disease exceed 400,000 cases worldwide. Lung squamous cell carcinoma (LUSC) has been recognized as the most common pathological form of lung cancer. The comprehensive understanding of molecular features related to LUSC progression has great significance in LUSC prognosis assessment and clinical management. In this study, we aim to identify a panel of signature genes closely associated with LUSC, which can provide novel insights into the progression of LUSC. Gene expression profiles were retrieved from public resources including gene expression omnibus (GEO) and the cancer genome atlas (TCGA) database. Differentially expressed genes (DEGs) between LUSC specimens and normal lung tissues were identified by bioinformatics analyses. A total of 66 DEGs were identified based on two cohorts of data. CytoHubba plugin of Cytoscape software was utilized for the further analyses of the top 10 candidate hub genes including OGN, ABI3BP, MAMDC2, FGF7, FAM107A, SPARCL1, DCN, COL14A1, and MFAP4 and CHRDL1, which showed significant downregulation in LUSC. Two LUSC cell lines were used to validate the functions of CHRDL1 and FAM107A through overexpression experiment. Together, our data revealed novel candidate tumor-suppressor genes in LUSC, suggesting previously unappreciated mechanisms in the progression of LUSC.

Establishment of a prognosis prediction model for lung squamous cell carcinoma related to PET/CT: basing on immunogenic cell death-related lncRNA

BackgroundImmunogenic cell death (ICD) stimulates adaptive immunity and holds significant promise in cancer therapy. Nevertheless, the influence of ICD-associated long non-coding RNAs (lncRNAs) on the prognosis of patients with lung squamous cell carcinoma (LUSC) remains unexplored.MethodsWe employed data from the The Cancer Genome Atlas (TCGA)database to identify ICD-related lncRNAs associated with the prognosis of LUSC using univariate Cox regression analysis. Subsequently, we utilized the LOSS regression model to construct a predictive risk model for assessing the prognosis of LUSC patients based on ICD-related lncRNAs. Our study randomly allocated187 TCGA patients into a training group and 184 patients for testing the predictive model. Furthermore, we conducted quantitative polymerase chain reaction (qPCR) analysis on 43 tumor tissues from LUSC patients to evaluate lncRNA expression levelsPearson correlation analysis was utilized to analyze the correlation of risk scores with positron emission tomography/computed tomography (PET/CT) parameters among LUSC patients.ResultsThe findings from the univariate Cox regression revealed 16 ICD-associated lncRNAs linked to LUSC prognosis, with 12 of these lncRNAs integrated into our risk model utilizing the LOSS regression. Survival analysis indicated a markedly higher overall survival time among patients in the low-risk group compared to those in the high-risk group. The area under the Receiver operating characteristic (ROC) curve to differentiate high-risk and low-risk patients was 0.688. Additionally, the overall survival rate was superior in the low-risk group compared to the high-risk group. Correlation analysis demonstrated a positive association between the risk score calculated based on the ICD-lncRNA risk model and the maximum standard uptake value (SUVmax) (r = 0.427, P = 0.0043) as well as metabolic volume (MTV)of PET-CT (r = 0.360, P = 0.0177) in 43 LUSC patients.ConclusionWe have successfully developed a risk model founded on ICD-related lncRNAs that proves effective in predicting the overall survival of LUSC patients.

Systematic analysis of apoptosis-related genes in the prognosis of lung squamous cell carcinoma: a combined single-cell RNA sequencing study.

Lung squamous cell carcinoma (LUSC) has a poor prognosis and lacks appropriate diagnostic and treatment strategies. Apoptosis dysregulation is associated with tumor occurrence and drug resistance, but the prognostic value of apoptosis-related genes (ARGs) in LUSC remains unclear. Using univariate Cox regression, least absolute shrinkage and selection operator (LASSO) regression, and multivariate Cox regression analysis based on differentially expressed ARGs, we constructed an ARG-related prognostic model for LUSC survival rates. We conducted correlation analysis of prognostic ARGs by incorporating the dataset of normal lung tissue from the Genotype-Tissue Expression (GTEx) database. We then constructed a risk model, and the predictive ability of the model was evaluated using receiver operating characteristic (ROC) curve analysis. Non-small cell lung cancer (NSCLC) single-cell RNA sequencing (scRNA-seq) data were downloaded from the Gene Expression Omnibus (GEO) database. Subsequently, these data were subjected to single-cell analysis. Cell subgroups were determined and annotated by dimensionality reduction clustering, and the cell subgroups in disease development were identified via pseudotemporal analysis with the Monocle 2 algorithm. We identified four significantly prognostic ARGs and constructed a stable prognostic risk model. Kaplan-Meier curve analysis showed that the high-risk group had a poorer prognosis (P<0.05). Furthermore, the ROC analysis of 3-, 5- and 7-year survival rates confirmed that the model had good predictive value for patients with LUSC. Single-cell RNA sequencing showed the prognostic ARGS were enriched in epithelial cells, smooth muscle cells, and T cells. Pseudotime analysis was used to infer the differentiation process and time sequence of cells. This study identified ARGs that are associated with prognosis in LUSC, and a risk model based on these prognostic genes was constructed that could accurately predict the prognosis of LUSC. Single-cell sequencing analysis provided new insights into the cellular-level development of tumors. These findings provide more guidance for the diagnosis and treatment of patients with LUSC.

NPLOC4 is a potential target and a poor prognostic signature in lung squamous cell carcinoma

Few prognostic biomarkers exist for lung squamous cell carcinoma (LUSC), which has a poor five-year survival rate. Using bioinformatics, this study evaluated NPLOC4 as a prognostic marker for patients with lung squamous cell carcinoma. Shorter survival periods and tumor growth were linked to high NPLOC4 expression.Disulfiram (DSF) combined with copper (Cu) targets NPLOC4 to achieve antitumor effects in lung squamous cell carcinoma. Thus, we investigated the effects of DSF with Cu in LUSC. Gene-set enrichment analysis identified ubiquitin-mediated proteolysis as the NPLOC4-associated mechanism influencing LUSC prognosis. In SK-MES-1 cell lines, DSF + Cu increased K48-linked ubiquitinated protein expression and apoptosis. This study identified NPLOC4 as a prognostic biomarker and a potential therapeutic target for LUSC.

Perilipin1 Expression as a Prognostic Factor in Patients with Squamous Cell Carcinoma of the Lung.

Perilipin (PLIN) is a major structural protein located on the surface of lipid droplets. PLIN plays an important role in human metabolism and is associated with metabolic diseases, such as obesity, diabetes, hypertension, and endocrine disorders. The dysregulation of lipid metabolism is one of the most prominent metabolic changes observed in cancers. Therefore, the PLIN protein family has recently attracted attention owing to its role in lipid metabolism and cancer. To date, no studies have addressed the association between the prognosis of lung cancer and PLIN1 expression. For the first time, we found that high PLIN1 expression was significantly correlated with worse disease-free survival (DFS) in lung squamous cell carcinoma (SCC). We examined PLIN1 expression by the immunohistochemical analysis of surgical lung SCC specimens obtained from 94 patients. We analyzed the correlation between PLIN1 expression, clinicopathological data, and patient survival, using a chi-squared test, Kaplan-Meier analysis with log-rank tests, and the multivariate Cox proportional hazards regression test. High PLIN1 expression was significantly correlated with lower DFS in the Kaplan-Meier analysis and the multivariate Cox proportional hazards regression model. High PLIN1 expression was significantly correlated with worse prognosis in lung SCC.

Identification of a new risk score model based on hypoxia and EMT-related genes for predicting lung squamous cell carcinoma prognosis.

A complicated analysis of the prognostic characteristics of lung squamous cell carcinoma (LUSC) is needed. The aim of this study was to develop a risk score model to predict immunotherapeutic response and prognosis for patients with LUSC. A hypoxia and epithelial-mesenchymal transition-related risk score model was developed for prediction of LUSC. The correlation between risk score and clinical characteristics was determined. The single sample gene set enrichment analysis algorithm was utilized to determine the abundance of cell infiltration in tumor immune microenvironment in LUSC. The predictive value of risk score model in response to immunotherapy was evaluated. A hypoxia and epithelial-mesenchymal transition-related risk score model was constructed. This risk score model was correlated with the overall survival of LUSC. Patients with low-risk presented a high survival possibility. The high-risk group was involved in ECM receptor interaction, complement and coagulation cascades, intestinal immune network for IgA production. Finally, patients with low-risk score had significant clinical benefit. The risk score model was constructed to predict immunotherapeutic response and prognosis for patients with LUSC. In addition to identifying LUSC patients with poor survival, the results provide more information for the immune immunotherapy and microenvironment for LUSC.

Mechanism Research of lncRNA miR143HG on Regulating the Biological Behavior of Lung Squamous Cell Carcinoma H520 Cells

There is a high morbidity, mortality, and poor clinical prognosis of lung squamous cell carcinoma (LUSC). However, there is currently no effective targeted treatment plan for LUSC. As a long non-coding RNA (lncRNA), lncRNA miR143HG has been proven to play an important role in the occurrence and development of various tumors. However, the biological role played by lncRNA miR143HG in LUSC cells is still unclear. Therefore, this study aimed to investigate the mechanism of lncRNA miR143HG on regulating the biological behavior of LUSC H520 cells. Pan-cancer analysis and differential expression analysis of lncRNA miR143HG were performed based on The Cancer Genome Atlas (TCGA) database. The predictive effect of lncRNA miR143HG on the diagnosis and prognosis of LUSC was evaluated by adopting the receiver operating characteristic (ROC) curve and timeROC curve. The enrichment degree of each pathway to lncRNA miR143HG was determined. The expression of lncRNA miR143HG and miR-155 in BEAS-2B cells and H520 cells was detected using quantitative real-time polymerase chain reaction (qRT-PCR). H520 cells were randomly divided into blank control group (without any treatment), negative control group (transfected with lncRNA-NC), lncRNA miR143HG group (transfected with lncRNA miR143HG), and lncRNA miR143HG+miR-155 group (co-transfected with lncRNA miR143HG and miR-155). The approaches of CCK-8, wound healing test, Transwell assay, flow cytometry, qRT-PCR, and Western blot were respectively employed to detect the cell proliferation ability, cell migration ability, cell invasion ability, cell apoptosis rate, and expression level of related genes and proteins of the Wnt/β-Catenin pathway. The results of pan-cancer analysis and differential analysis collectively showed that except for renal clear cell carcinoma, the expression of lncRNA miR143HG in other cancer tissues was higher than that in healthy tissues, and the differences were significant in LUSC. The evaluation results of the ROC curve and timeROC curve suggested that lncRNA miR143HG was of great significance in the prediction of diagnosis and prognosis of LUSC. The pathways enriched in high expression of lncRNA miR143HG mainly included focal adhesion, vascular smooth muscle contraction, calcium signaling pathways, and so on; the pathways enriched in the low expression of lncRNA miR143HG embraced oxidative phosphorylation, cell cycle, basic transcription factors, etc. The qRT-PCR results showed that lncRNA miR143HG was low expressed but miR-155 was highly expressed in H520 cells when compared to BEAS-2B cells (P<0.05). Compared with the negative control group, the expression levels of the gene of lncRNA miR143HG, the gene and protein of Wnt, as well as the gene and protein of β-Catenin were significantly increased, while the gene expression of miR-155, the ability of cell proliferation, cell migration, and cell invasion were significantly reduced, but the cell apoptosis rate was dominantly elevated in cells of lncRNA miR143HG group (P<0.05). In addition, compared with the lncRNA miR143HG group, overexpression of miR-155 could reverse the biological behavior mediated by lncRNA miR143HG, and the difference was statistically significant (P<0.05). LncRNA miR143HG was of great significance for the biological behavior of H520 cells. LncRNA miR143HG inhibited the ability of proliferation, migration, and invasion, as well as enhanced the apoptosis of H520 cells by downregulating miR-155 expression, which may be related to the Wnt/β-Catenin pathway. .

Identification of specific prognostic markers for lung squamous cell carcinoma based on tumor progression, immune infiltration, and stem index.

Lung squamous cell carcinoma (LUSC) is a unique subform of nonsmall cell lung cancer (NSCLC). The lack of specific driver genes as therapeutic targets leads to worse prognoses in patients with LUSC, even with chemotherapy, radiotherapy, or immune checkpoint inhibitors. Furthermore, research on the LUSC-specific prognosis genes is lacking. This study aimed to develop a comprehensive LUSC-specific differentially expressed genes (DEGs) signature for prognosis correlated with tumor progression, immune infiltration,and stem index. RNA sequencing data for LUSC and lung adenocarcinoma (LUAD) were extracted from The Cancer Genome Atlas (TCGA) data portal, and DEGs analyses were conducted in TCGA-LUSC and TCGA-LUAD cohorts to identify specific DEGs associated with LUSC. Functional analysis and protein-protein interaction network were performed to annotate the roles of LUSC-specific DEGs and select the top 100 LUSC-specific DEGs. Univariate Cox regression and least absolute shrinkage and selection operator regression analyses were performed to select prognosis-related DEGs. Overall, 1,604 LUSC-specific DEGs were obtained, and a validated seven-gene signature was constructed comprising FGG, C3, FGA, JUN, CST3, CPSF4, and HIST1H2BH. FGG, C3, FGA, JUN, and CST3 were correlated with poor LUSC prognosis, whereas CPSF4 and HIST1H2BH were potential positive prognosis markers in patients with LUSC. Receiver operating characteristic analysis further confirmed that the genetic profile could accurately estimate the overall survival of LUSC patients. Analysis of immune infiltration demonstrated that the high risk (HR) LUSC patients exhibited accelerated tumor infiltration, relative to low risk (LR) LUSC patients. Molecular expressions of immune checkpoint genes differed significantly between the HR and LR cohorts. A ceRNA network containing 19 lncRNAs, 50 miRNAs, and 7 prognostic DEGs was constructed to demonstrate the prognostic value of novel biomarkers of LUSC-specific DEGs based on tumor progression, stemindex, and immune infiltration. In vitro experimental models confirmed that LUSC-specific DEG FGG expression was significantly higher in tumor cells and correlated with immune tumor progression, immune infiltration, and stem index. In vitro experimental models confirmed that LUSC-specific DEG FGG expression was significantly higher in tumor cells and correlated with immune tumor progression, immune infiltration, and stem index. Our study demonstrated the potential clinical implication of the 7- DEGs signature for prognosis prediction of LUSC patients based on tumor progression, immune infiltration, and stem index. And the FGG could be an independent prognostic biomarker of LUSC promoting cell proliferation, migration, invasion, THP-1 cell infiltration, and stem cell maintenance.

Establishment of a prognostic model towards lung squamous cell carcinoma based on m7G-related genes in TCGA.

Lung squamous cell carcinoma (LUSC) is a non-small cell lung cancer with a poor prognosis owing to late diagnosis. New molecular markers are urgently needed to improve the diagnosis and prognosis of LUSC. 7-Methylguanosine (m7G) modifications-a transfer RNA (tRNA) modification-are common in eubacteria, eukaryotes, and a few archaea. These modifications promote the turnover and stability of some mRNAs to prevent mRNA decay, improve translation efficiency, and reduce ribosomal pausing but are associated with poor survival in human cancer cells. However, the expression of m7G-related genes in LUSC and their association with prognosis remain unclear. In this study, we identified nine differentially expressed genes related to prognosis by comparing the expression profiles of tumor tissues (502 LUSC reports) with normal tissues (49 adjacent non-tumor lung tissue reports). The genes included six upregulated (KLK7, LCE3E, AREG, KLK6, ZBED2, and MAPK4) and three downregulated (ADH1C, NTS, and ERLIN2) genes. Based on these nine genes, patients with LUSC were classified into low- and high-risk groups to analyze the trends in prognosis. We found that the nine m7G-related genes play important roles in immune regulation, hormone regulation, and drug sensitivity through pathways, including antigen processing and presentation, adherent plaques, ECM receptor interactions, the drug metabolism of cytochrome p450, and the metabolism of cytochrome p450 to xenobiotics; the functions of these genes are likely accomplished in part by m6A modifications. The effect of m7G-related genes on the diagnosis and prognosis of LUSC was further indicated by population analysis.

Downregulation of VRK1 Inhibits Progression of Lung Squamous Cell Carcinoma through DNA Damage.

Lung squamous cell carcinoma (LUSC) is a common malignancy. And the antitumor effect of bovine pox virus-associated kinase 1 (VRK1) is becoming a hot research topic. VRK1 expression and prognosis in LUSC were analyzed using the GEPIA database. The expression of VRK1 mRNA was detected in 25 LUSC clinical tissue samples by RT-PCR. VRK1 shRNA was transfected into LUSC NCI-H520 and SK-MES-1 cell lines to interfere with VRK1 expression, and the efficiency of VRK1 shRNA interference was detected by the western blot. The effects of VRK1 downregulation on LUSC cell viability, migration, cell cycle, and apoptosis were analyzed by the CCK8 assay, scratch assay, transwell assay, and flow cytometry. The effect of VRK1 downregulation on DNA damage response (DDR) was examined by immunofluorescence staining and western blot assays and further validated by in vivo experiments. VRK1 was highly expressed in both LUSC tissues and cells. Survival analysis showed that the overall survival of LUSC patients with high VRK1 expression was significantly lower than that of LUSC patients with low VRK1 expression (P=0.0026). The expression level of the VRK1 gene was significantly higher in cancer tissues of LUSC patients than in paracancerous tissues. After transfection of VRK1 shRNA in both LUSC cells, cell activity decreased (P < 0.001), migration ability started to be inhibited (P < 0.001), the ratio of G0/G1 phase cells increased (P < 0.001), and apoptosis rate increased (P < 0.001). Immunofluorescence and western blot results showed that shVRK1 increased the level of γ-H2A.X (P < 0.001) and promoted apoptosis of tumor cells (P < 0.001). In addition, the results of animal experiments showed that shVRK1 had antitumor effects (P < 0.001) and a combined effect with DOX (P < 0.001). The downregulation of VRK1 significantly affected the proliferation, apoptosis, migration, and cell cycle progression of LUSC cells via DDR, suggesting that VRK1 is a suitable target for potential LUSC therapy.

Characterization of platelet-related genes and constructing signature combined with immune-related genes for predicting outcomes and immunotherapy response in lung squamous cell carcinoma.

Lung squamous cell carcinoma (LUSC) is a highly malignant subtype of non-small cell lung cancer with poor prognosis. Platelets are known to play a critical role in cancer development and progression, and recent studies suggest that they can also regulate immune response in tumors. However, the relationship between platelet-related genes (PRGs) and LUSC prognosis and tumor microenvironments remains unclear. In this study, we used multiple bioinformatics algorithms to identify 25 dysregulated PRGs that were significantly associated with LUSC prognosis. We found that PRGs were involved in multiple biological processes, particularly in the tumor microenvironment, and that platelet-related scores (PRS) were a risk factor. Additionally, we established a 6-gene prognostic signature combining PRGs and immune-related genes that accurately predicted outcomes and immunotherapy efficacy in LUSC patients. Our study provides a comprehensive analysis of the biological functions and potential therapeutic targets of PRGs in LUSC, which may inform the development of new treatments for this disease.

Exploration of the Perturbation of PKIG in Lung Squamous Cell Carcinoma and the Role in Tumor Microenvironment Based on Bioinformatics Method

Lung cancer is the leading cause of cancer-related death worldwide, and patients have limited survival benefits from traditional treatments such as surgery, radiotherapy and chemotherapy. As a new treatment for lung cancer, immunotherapy has significantly prolonged the overall survival (OS) of patients. However, only some patients can benefit from it. We need to explore immunotherapy biomarkers more deeply to screen for advantages. The original data were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database, and the immunological and prognostic genes of lung squamous cell carcinoma (LUSC) were screened using R software and TIMER database. The expression of target genes was studied in TCGA and GEO databases, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and correlation analysis with tumor immune characteristics were performed by R software and TISIDB database. We screened out a gene related to immunity and prognosis, cAMP dependent protein kinase inhibitor γ (PKIG), which is significantly differentially expressed in LUSC and normal tissues, and has important reference value for the diagnosis and prognosis assessment of LUSC. PKIG differential genes are mainly concentrated in the regulation of humoral immune response and other processes. The expression of PKIG was positively correlated with the infiltration level of regulatory T cells (Tregs) (r=0.340, P<0.001). In addition, the expression level of PKIG was positively correlated with the expression of chemokines/chemokine receptors such as chemokine C-C motif ligand 2 (CCL2) (r=0.503, P<0.001), CXC chemokine ligand 12 (CXCL12) (r=0.386, P<0.001) and CXC-chemokine receptor 4 (CXCR4) (r=0.492, P<0.001), and immunoinhibitors such as programmed cell death protein 1 (PDCD1) (r=0.359, P<0.001), cytotoxic T-lymphocyte associated antigen 4 (CTLA4) (r=0.375, P<0.001) and T cell immunoglobulin and ITIM domains (TIGIT) (r=0.305, P<0.001) in LUSC. The immunological and prognostic gene PKIG in lung squamous cell carcinoma was screened through bioinformatics analysis. PKIG is highly correlated with LUSC prognosis and immune microenvironment, and is expected to be a potential biomolecular marker for LUSC immunotherapy.