Prognostic Biomarker For Lung Cancer Research Articles

Prognostic significance of LINC01132 in lung cancer and its regulatory role in tumor progression

BackgroundThe application of long non-coding RNAs (lncRNAs) in cancer has been the focus of research in recent years. This study aimed to discuss the expression and functional mechanism of lncRNA LINC01132 (LINC01132) in lung cancer and explore its prognostic significance in tumors.MethodsThe expression of LINC01132 in lung cancer patients was verified using GSE98929 screening and real-time quantitative polymerase chain reaction (RT-qPCR) detection. The prognostic potential of LINC01132 was evaluated by performing the chi-square analysis of clinical indicators, Kaplan–Meier analysis, and Cox proportional hazard model. Cell Counting Kit-8 (CCK-8), flow cytometry, and Transwell assay were used to characterize the biological functions of the lung cancer cells. The targeting relationship between LINC01132 and microRNA-125a-3p (miR-125a-3p), miR-125a-3p and SMAD2 was predicted by bioinformatics and verified by luciferase activity assay.ResultsLINC01132 was upregulated in lung cancer tissues and cells, which was an independent risk factor for survival and prognostic outcomes of lung cancer patients. Silencing LINC01132 suppressed the proliferation and migration of lung cancer cells and accelerated cell death. The target of LINC01132 was miR-125a-3p, and miR-125a-3p inhibitor could eliminate the inhibitory effect of LINC01132 knockdown on the cells. Additionally, SMAD2 is a downstream target of miR-125a-3p, and knockdown of SMAD2 reversed the effects of miR-125a-3p inhibitor on cell migration and invasion.ConclusionLINC01132 may regulate the progression of lung cancer by targeting the miR-125a-3p /SMAD2 axis and serve as a prognostic biomarker for lung cancer.

PKM2 is a potential prognostic biomarker and related to immune infiltration in lung cancer

Pyruvate kinase M2 (PKM2), a subtype of pyruvate kinase, plays a crucial role as a key enzyme in the final step of glycolysis. It is involved in regulating the tumor microenvironment and accelerating tumor progression. However, the relationship between PKM2 expression and the prognosis and immune infiltration remains unclear in lung cancer. In this study, we analyzed PKM2 expression in pan-cancer, and investigated its association with prognosis and immune cell infiltration of lung cancer by using multiple online databases, including Gent2, Tumor Immune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), PrognoScan, Kaplan–Meier plotter, and The Human Protein Atlas (HPA). The results showed that PKM2 expression is elevated in tumor tissues compared with the adjacent normal tissues of most cancers, including lung cancer. Prognostic analysis indicated that high expression of PKM2 was associated with poorer prognosis in overall lung cancer patients, especially in lung adenocarcinoma (LUAD). Notably, PKM2 exhibited a strong correlation with B cells and CD4+ T cells in LUAD; and with B cells, CD8+ T cells, CD4+ cells, and macrophages in lung squamous cell carcinoma (LUSC). Furthermore, PKM2 expression displayed a significant negative correlation with the expression of immune cell markers in both LUAD and LUSC. These findings suggested that PKM2 could serve as a promising prognostic biomarker for lung cancer and provided insights into its essential role in modulating the immune cell infiltration.

Serum ferritin level is an effective prognostic factor for lung cancer immunotherapy

ABSTRACT Immunotherapy of lung cancer has achieved promising clinical results. However, it is urgent to develop predictive biomarkers for effective immunotherapy. While ferroptosis plays a critical role in immunotherapy efficacy, ferritin is an important regulatory factor. We, therefore, hypothesize that basal serum ferritin levels before immunotherapy and their corresponding changes during immunotherapy can be useful predictors of immunotherapy response in patients with lung cancer. We measured serum ferritin levels in 107 patients with lung cancer before and during immune checkpoint blockade treatments and studied the correlation between ferritin levels, response rate, and survival. Moreover, the correlation between basal ferritin and PD-L1 expression, tumor stages and pathological types was also analyzed. Patients with lower basal serum ferritin levels before immunotherapy had longer progression-free survival (PFS) (median 7 vs 4 months, P = .023) and higher disease control rate (DCR) (X2 = 4.837, P = .028), those with downregulated serum ferritin levels during immunotherapy correlated with longer PFS (median 9.5 vs 4 months, P < .001) and higher DCR (X2 = 6.475, P = .011). However, the “integrated factor”, which was calculated as the combination of lower basal serum ferritin levels before immunotherapy and downregulated serum ferritin levels during immunotherapy, correlated with prolonged PFS (P < .001). Multivariate analyses revealed that the basal serum ferritin levels before immunotherapy and the corresponding changes during immunotherapy were both strong independent prognostic factors (hazard ratio (HR) = 1.60, P = .041; HR = 2.65, P = .001). These findings suggest that serum ferritin levels can be used as a prognostic biomarker for lung cancer in predicting immunotherapy efficacy.

The combination of PD-L1 expression and the neutrophil-to-lymphocyte ratio as a prognostic factor of postoperative recurrence in non-small-cell lung cancer: a retrospective cohort study

BackgroundWhile PD-L1 expression and neutrophil-to-lymphocyte ratio (NLR) are prognostic biomarkers for lung cancer, few studies have considered their interaction. We hypothesized that the product of PD-L1 expression (tumor proportion score) and the NLR (PD-L1 × NLR) might be a postoperative prognostic marker reflecting the immune microenvironment of lung cancer.MethodsWe analyzed the association between PD-L1 × NLR and postoperative recurrence-free survival in 647 patients with NSCLC using multivariable Cox proportional hazards models.ResultsIn the analysis of PD-L1 × NLR as a categorical variable, the group with PD-L1 × NLR ≥ 25.8 had a significantly higher hazard ratio (HR) than the group with < 25.8 (adjusted HR 1.78, 95% confidence interval [CI] 1.23–2.60). The adjusted HR for PD-L1 × NLR, considered a continuous variable, was 1.004 (95% CI, 1.002–1.006). The risk of postoperative recurrence increased by 1.004-fold for each unit increase in PD-L1 × NLR, and a more than 2-fold increase in risk was observed for values ≥ 170.ConclusionsPD-L1 × NLR may be used in real-world clinical practice as a novel factor for predicting the risk of postoperative recurrence after lung cancer surgery.

Long non-coding RNA signatures in non-small cell lung cancer and their clinicopathological significance

Lung cancer is the most common type of cancer in our country and worldwide, and it is a leading cause of cancer-related deaths. According to the latest global cancer statistics, lung cancer was identified as the second most common type of cancer, and the leading cause of cancer-related deaths. Long non-coding RNAs (lncRNAs) are a highly heterogeneous class of RNA molecules sharing many characteristics with mRNAs, except for the protein-coding potential. Accumulating mass of evidence suggest that lncRNAs play key regulatory roles during the multistep formation of human cancers including lung cancer. In previous studies, it has been shown that many lncRNA molecules play significant roles in the formation and progression of lung cancer. However, there are still numerous lncRNA molecules in lung cancer whose roles remain unknown. Accordingly, here we sought to ascertain the diagnostic and prognostic value of lncRNAs by analyzing the expression profiles of THRIL, NEAT1, and LOC105376095 in lung cancer. Remarkably, NEAT1 and LOC105376095 but not THRIL were identified to be differentially expressed in tissues of lung tumors. More importantly, LOC105376095, a yet uncharacterized lncRNA molecule, was significantly associated with the disease severity. Collectively, NEAT1 and LOC105376095 hold promise as potential diagnostic and prognostic biomarkers for lung cancer, presenting opportunities for targeted therapeutic interventions in the future.

B-365 Serum MAGE-A3 and MAGE-A4 Protein Levels as Potential Prognostic Biomarkers for Lung Cancer

Abstract Background Melanoma-associated antigen 3 (MAGE-A3) and MAGE-A4 are members of Melanoma Antigen Gene (MAGE) family, which have restricted expression to the testis and are abnormally expressed in cancer cells. MAGE-A3 and MAGE-A4 are overexpressed in lung cancer and have been shown to be associated with cancer progression and poor prognosis. Elevated MAGE-A4 protein level in lung cancer serum samples has been reported in the literature, however, it is unclear whether MAGE-A3 protein can be detected in serum samples of lung cancer patients. Methods We developed human MAGE-A3 and MAGE-A4 sandwich ELISA kits and used them to measure serum MAGE-A3 and MAGE-A4 protein levels in 21 lung cancer patients and 30 non-cancer controls. Results Serum MAGE-A3 protein was detected in all 21 lung cancer patients (range: 34 to 78871 pg/mL, mean: 5600 pg/mL) and was significantly elevated compared to non-cancer controls (range: 23–308 pg/mL, mean: 140 pg/mL) (P &amp;lt; 0.05). Serum MAGE-A4 protein was detected in 5 of 21 (24%) lung cancer patients (range: 280 to 35096 pg/mL, mean: 1819 pg/mL), and the samples with high serum MAGE-A4 concentration matched those with high serum MAGE-A3 concentration. Serum MAGE-A4 protein was not detectable in non-cancer controls. Conclusion Our findings suggest that serum MAGE-A3 and MAGE-A4 may serve as potential prognostic biomarkers for lung cancer. The detection of elevated serum MAGE-A3 and MAGE-A4 in lung cancer patients indicates their specificity for the disease. Larger studies with more samples, different cancer stages, and longer follow-up are needed to validate these results and establish the clinical utility of serum MAGE-A3 and MAGE-A4 levels as prognostic markers for lung cancer. If further validated, these biomarkers could aid in early diagnosis and better management of lung cancer.

Prognostic role of C-reactive protein to albumin ratio in lung cancer: An updated systematic review and meta-analysis.

C-reactive protein to albumin ratio (CRP/Alb ratio, CAR) has been suggested as a potential prognostic biomarker in lung cancer. This updated systematic review and meta-analysis aimed to assess the association between CAR and lung cancer prognosis in current literature. A systematic search of databases was conducted to identify relevant studies published up to April 2023. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to assess the association between CAR and overall survival (OS) and progression-free survival (PFS) and recurrence-free survival (RF) in lung cancer patients. This meta-analysis includes 16 studies with a total of 5337 patients, indicating a significant association between higher CAR and poorer OS, PFS, and RFS in lung cancer patients, with a pooled HR of 1.78 (95% CI = 1.60-1.99), 1.57 (95% CI = 1.36-1.80), and 1.97 (95% CI = 1.40-2.77), respectively. This updated meta-analysis provides evidence for the potential prognostic role of CAR in lung cancer, suggesting its utility as an effective and noninvasive biomarker for identifying high-risk patients and informing treatment decisions in a cost-effective manner. However, further large-scale studies will be necessary to establish the optimal cut-off value for CAR in lung cancer and confirm the present findings.

The Association of IFN-γ, TNF-α, and Interleukins in Bronchoalveolar Lavage Fluid with Lung Cancer: A Prospective Analysis.

Lung cancer is a leading cause of cancer-related mortality worldwide. Identifying novel diagnostic and prognostic biomarkers is essential for improving patient outcomes. This study aimed to investigate the predictive role of cytokines from bronchoalveolar lavage fluid (BALF) in lung cancer diagnosis and prognosis. A prospective study was conducted on 33 patients with suspected lung cancer, divided into inflammatory and non-inflammatory BALF groups. Inflammatory markers in BALF were assessed, and their association with lung cancer risk was analyzed using receiver operating characteristic (ROC) plot analysis, sensitivity and specificity percentages, and regression analysis. Statistically significant differences were observed between the inflammatory and non-inflammatory groups for several inflammatory markers, including IFN-gamma, IL-1b, IL-2, IL-6, IL-10, and IL-12p70. In the follow-up analysis, significant differences persisted for IFN-gamma, IL-1b, IL-2, IL-4, and IL-6. ROC plot analysis revealed that IL-12p70 had the highest area under the curve (AUC) value (0.702), followed by IL-2 (0.682), IL-6 (0.620), IL-4 (0.611), TNF-alpha (0.609), IL-10 (0.604), IL-1b (0.635), and IFN-gamma (0.521). IL-6 showed the highest sensitivity (73%), and IL-1b had the highest specificity (69%). Regression analysis demonstrated that IL-6 (cut-off = 25 pg/mL) and IL-12p70 (cut-off = 30 pg/mL) had the highest odds ratios for lung cancer risk, at 5.09 (95% CI: 2.38-9.24, p < 0.001) and 4.31 (95% CI: 1.85-8.16, p < 0.001), respectively. Cytokines from BALF, particularly IL-6 and IL-12p70, show potential as diagnostic and prognostic biomarkers for lung cancer. Further studies with larger cohorts are warranted to confirm these findings and elucidate the clinical implications of these markers in lung cancer management.

Diagnostic Utility and Tendency of Bronchial and Serum Soluble Receptor for Advanced Glycation EndProducts (sRAGE) in Lung Cancer.

The receptor for advanced glycation end-products (RAGE) may serve as a diagnostic and prognostic biomarker of lung cancer and lung injury. We explored whether the serum and bronchial levels of soluble RAGE (sRAGE) distinguished infectious lung diseases from lung cancer. We collected serum and bronchial washing fluids (BWFs) from patients diagnosed with pneumonia, tuberculosis, or preoperative lung cancer from April 2016 to March 2022. sRAGE levels were measured using an enzyme-linked immunosorbent assay and we drew receiver operating characteristic (1) curves to determine the cut-off values affording the best diagnostic sensitivities. We enrolled 81 patients including 20 with tuberculosis, 30 with pneumonia, and 31 with lung cancer. Of the 81, 61% were males and the median age was 66 years. The median serum level of sRAGE was 822 (678-1168 pg/mL) and did not differ significantly between the three groups. The median bronchial sRAGE level was 167 (83-529 pg/mL) but 231 (108-649 pg/mL) for tuberculosis, 366 (106-706 pg/mL) for pneumonia, and 103 (32-254 pg/mL) for lung cancer patients (p = 0.018). The ROC curve for the bronchial sRAGE values of lung cancer patients revealed that the optimal cut-off was 118.9 pg/mL. This afforded a sensitivity of 76%, a specificity of 58%, and an area under the ROC curve of 0.695 (p = 0.005). The level of bronchial sRAGE differed significantly between patients with lung cancer and other respiratory diseases; that level may serve as an auxiliary diagnostic biomarker.

S-adenosylhomocysteine hydrolase-like protein 1 (AHCYL1) inhibits lung cancer tumorigenesis by regulating cell plasticity

BackgroundLung cancer is one of the most frequently diagnosed cancers characterized by high mortality, metastatic potential, and recurrence. Deregulated gene expression of lung cancer, likewise in many other solid tumors, accounts for their cell heterogeneity and plasticity. S-adenosylhomocysteine hydrolase-like protein 1 (AHCYL1), also known as Inositol triphosphate (IP(3)) receptor-binding protein released with IP(3) (IRBIT), plays roles in many cellular functions, including autophagy and apoptosis but AHCYL1 role in lung cancer is largely unknown.ResultsHere, we analyzed the expression of AHCYL1 in Non-Small Cell Lung Cancer (NSCLC) cells from RNA-seq public data and surgical specimens, which revealed that AHCYL1 expression is downregulated in tumors and inverse correlated to proliferation marker Ki67 and the stemness signature expression. AHCYL1-silenced NSCLC cells showed enhanced stem-like properties in vitro, which correlated with higher expression levels of stem markers POU5F1 and CD133. Also, the lack of AHCYL1 enhanced tumorigenicity and angiogenesis in mouse xenograft models highlighting stemness features.ConclusionsThese findings indicate that AHCYL1 is a negative regulator in NSCLC tumorigenesis by modulating cell differentiation state and highlighting AHCYL1 as a potential prognostic biomarker for lung cancer.

Inflammatory Markers in Lung CancerA Comparative Cross-sectional Study

Introduction: Lung cancer is the most common cause of cancer mortality worldwide, principally because of its late diagnosis. Chronic inflammation plays a significant role in tumour growth and progression via increasing the levels of inflammatory markers in blood. Inflammatory markers are expected to be valuable prognostic biomarkers in cancer. Markers like Absolute Neutrophil Count (ANC), Absolute Lymphocyte Count (ALC), platelet count, Neutrophil Lymphocyte Ratio (NLR) and Platelet Lymphocyte Ratio (PLR) may aid in assessing prognosis of lung cancer. Aim: To study the inflammatory markers (ANC, ALC, Platelet count, NLR and PLR) in lung cancer and correlate these markers with cancer stage and histopathological type. Materials and Methods: A hospital-based cross-sectional study was conducted in lung cancer patients at Institute of Respiratory Diseases, SMS Medical College, Jaipur, Rajasthan, India. Sixty patients with lung cancer and sixty controls were included. The clinical characteristics, ANC, ALC, platelet count, NLR and PLR of cases and controls were assessed and compared. Also, the comparison of these inflammatory markers with Tumor, Nodes and Metastases (TNM) staging and histopathological type of lung cancer were documented and results were interpreted. The data analysis was done with the use of Statistical Package for Social Sciences (SPSS) software, IBM manufacturer, Chicago, USA, (Ver.) 26. Results: Mean age (years) of the case and control groups was 60.17 and 61.03, respectively. Distribution of gender in cases and controls was comparable. The major histology of lung cancer was Non-Small Cell Lung Cancer (NSCLC, 81.66%) out of which squamous cell carcinoma constituted 55.00% and adenocarcinoma 21.67%, followed by small cell carcinoma at 18.33%. Overall, 46.67% of the patients belonged to TNM staging IVA followed by IIIB (25.00%). The levels of ANC, platelet count, NLR and PLR were significantly elevated and ALC was decreased in cases as compared to control. There was no statistically significant association between the inflammatory markers ANC, ALC, platelet counts, NLR and PLR with the histopathological type of lung cancer. Mean ANC, platelet count, NLR and PLR were found to be significantly elevated in late stages of lung cancer, whereas, ALC had no such association with the stages of lung cancer. Conclusion: Inflammatory markers (ANC, platelet count, NLR, PLR, ALC) can serve as valuable prognostic biomarkers in lung cancer and can easily be used in resource-limited areas.

MicroRNA-21 as a diagnostic and prognostic biomarker of lung cancer: a systematic review and meta-analysis.

Background: The relationship between microRNA-21 (miRNA-21) and pathogenesis of lung cancer is a considerable focus of research interest. However, to our knowledge, no in-depth meta-analyses based on existing evidence to ascertain the value of miRNA-21 in diagnosis and clinical prognosis of lung cancer have been documented.Methods: We comprehensively searched all the literature pertaining to ‘miRNA-21’ and ‘lung cancer’ from four databases from the period of inception of each database until May 2020. Using specific inclusion and exclusion criteria, the literature for inclusion was identified and the necessary data extracted.Results: In total, 46 articles were included in the meta-analysis, among which 31 focused on diagnostic value and 15 on prognostic value. Combined sensitivity (SEN) of miRNA-21 in diagnosis of lung cancer was 0.77 (95% confidence interval (CI): 0.72–0.81), specificity (SPE) was 0.86 (95% CI: 0.80–0.90), diagnostic odds ratio (DOR) was (95% CI: 12–33), and area under the SROC curve (AUC) was 0.87 (95% CI: 0.84–0.90). No significant correlations were observed between abnormal expression of miRNA-21 and gender, smoking habits, pathological type and clinical stage of lung cancer (P>0.05). In terms of overall survival (OS), univariate analysis (hazards ratio (HR) = 1.49, 95% CI: 1.22–1.82) revealed high expression of miRNA-21 as an influencing factor for lung cancer. MiRNA-21 was confirmed as an independent risk factor for poor prognosis in multivariate analysis (HR = 1.65, 95% CI: 1.24–2.19).Conclusion: MiRNA-21 has potential clinical value in the diagnosis and prognosis of lung cancer and may serve as an effective diagnostic marker and therapeutic target in the future.

Analysis of prognostic and therapeutic values of drug resistance-related genes in the lung cancer microenvironment.

BackgroundThe interaction between cancer cells and stromal cells has a significant contribution in tumorigenesis and tumor development, and plays an anti-tumor immune effect under the regulation of drug resistance-related genes, which affects the outcome of patients. Coiled-coil domain-containing protein 73 (CCDC73), DLG associated protein 1 (DLGAP1), dermatan sulfate epimerase like (DSEL), estrogen receptor 1 (ESR1), and SEC14-like 5 (SEC14L5) were identified as drug resistance-related genes in lung cancer. However, these genes have no clear value in lung cancer in terms of expression and prognosis.MethodsONCOMINE, GEPIA, UALCAN, cBioPortal, GeneMANIA, STRING, and TIMER were utilized in this study.ResultsThe transcriptional expression level of DLGAP1 was remarkably decreased in lung cancer tissues, while the transcriptional level of SEC14L5 was significantly increased. The pathological stage of lung adenocarcinoma (LUAD) was tightly correlated with the expression of SEC14L5. The lung cancer patients with high transcription level of CCDC73 gene tended to have a good prognosis. The function of drug resistance-related genes is mainly related to RNA polymerization. Our results showed that infiltration of six types of immune cells (dendritic cells, macrophages, neutrophils, B cells, CD4+ T cells, and CD8+ T cells) significantly correlated with the expression of these drug resistance-related genes.ConclusionsNovel screening for immunotherapy targets and prognostic biomarkers in lung cancer may draw inspiration from our results.

Extracellular domain of semaphorin 5A serves a tumor‑suppressing role by activating interferon signaling pathways in lung adenocarcinoma cells.

Semaphorin 5A (SEMA5A), which was originally identified as an axon guidance molecule in the nervous system, has been subsequently identified as a prognostic biomarker for lung cancer in nonsmoking women. SEMA5A acts as a tumor suppressor by inhibiting the proliferation and migration of lung cancer cells. However, the regulatory mechanism of SEMA5A is not clear. Therefore, the purpose of the present study was to explore the roles of different domains of SEMA5A in its tumor‑suppressive effects in lung adenocarcinoma cell lines. First, it was revealed that overexpression of full length SEMA5A or its extracellular domain significantly inhibited the proliferation and migration of both A549 and H1299 cells using MTT, colony formation and gap closure assays. Next, microarray analyses were performed to identify genes regulated by different domains of SEMA5A. Among the differentially expressed genes, the most significant function of these genes that were enriched was the 'Interferon Signaling' pathway according to Ingenuity Pathway Analysis. The activation of the 'Interferon Signaling' pathway was validated by reverse transcription‑quantitative PCR and western blotting. In summary, the present study demonstrated that the extracellular domain of SEMA5A could upregulate genes in interferon signaling pathways, resulting in suppressive effects in lung adenocarcinoma cells.

Systemic analysis the expression, prognostic, and immune infiltrates significance of MS4A family in lung cancer

With its high incidence and mortality rate, lung cancer is one of the malignancies that poses the greatest threat to the health and life of the population. Mounting research found that the Membrane-spanning 4A (MS4A) family took part in tumor development. Nevertheless, the expression and prognostic value of the MS4A family genes in lung cancer remained unclear. Compared with normal tissues, the transcript levels of MS4A2, MS4A4A, MS4A4E, MS4A6A, MS4A6E, MS4A7, MS4A8, MS4A14, and MS4A15 were significantly decreased in lung cancer tissues, and there was a significant correlation between MS4A2, MS4A8, MS4A15, and the pathological stage of lung cancer patients. Survival analysis has shown that lung cancer patients with lower mRNA expression levels of MS4A2, MS4A4E, and MS4A15 had poorer prognosis. The function of MS4A family genes was primarily involved in immune-related pathways. Based on the results, it was indicated that the expression of the MS4A family was significantly correlated with the infiltration of immune cells (B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells). In conclusions, our research indicated that MS4A family might become a new immunotherapy target and prognostic biomarker for lung cancer.

Oncogenic circRNA C190 Promotes Non-Small Cell Lung Cancer via Modulation of the EGFR/ERK Pathway.

Lung cancers are the leading cause of cancer-related mortality worldwide, and the majority of lung cancers are non-small cell lung carcinoma (NSCLC). Overexpressed or activated EGFR has been associated with a poor prognosis in NSCLC. We previously identified a circular noncoding RNA, hsa_circ_0000190 (C190), as a negative prognostic biomarker of lung cancer. Here, we attempted to dissect the mechanistic function of C190 and test the potential of C190 as a therapeutic target in NSCLC. C190 was upregulated in both NSCLC clinical samples and cell lines. Activation of the EGFR pathway increased C190 expression through a MAPK/ERK-dependent mechanism. Transient and stable overexpression of C190 induced ERK1/2 phosphorylation, proliferation, and migration in vitro and xenograft tumor growth in vivo. RNA sequencing and Expression2Kinases (X2K) analysis indicated that kinases associated with cell-cycle and global translation are involved in C190-activated networks, including CDKs and p70S6K, which were further validated by immunoblotting. CRISPR/Cas13a-mediated knockdown of C190 decreased proliferation and migration of NSCLC cells in vitro and suppressed tumor growth in vivo. TargetScan and CircInteractome databases predicted that C190 targets CDKs by sponging miR-142-5p. Analysis of clinical lung cancer samples showed that C190, CDK1, and CDK6 expressions were significantly higher in advanced-stage lung cancer than in early-stage lung cancer. In summary, C190 is directly involved in EGFR-MAPK-ERK signaling and may serve as a potential therapeutic target for the treatment of NSCLC. SIGNIFICANCE: The circRNA C190 is identified as a mediator of multiple pro-oncogenic signaling pathways in lung cancer and can be targeted to suppress tumor progression.

Diagnostic value of periostin in lung cancer-related malignant pleural effusion.

Periostin (POSTN) is an extracellular matrix protein that is overexpressed in lung cancer and is considered an effective diagnostic and prognostic biomarker for lung cancer. The purpose of this study was to investigate the diagnostic performance of POSTN and to further evaluate the diagnostic value of POSTN combined with carcinoembryonic antigen (CEA) and cancer ratio [CR: serum lactate dehydrogenase (LDH)/pleural effusion adenosine deaminase (PE ADA)] in lung cancer-related malignant PE (MPE). A total of 108 patients with PE, including 54 with lung cancer and 54 with benign lung disease, were enrolled in this study. The POSTN levels of PE and serum were detected using an enzyme-linked immunosorbent assay. Information on the expression of PE and serum CEA, serum LDH, and PE ADA was collected from medical records. The levels of PE POSTN in MPE of patients with lung cancer were significantly higher than those in patients with benign PE (p<0.0001). The receiver operating characteristic (ROC) curve indicated that the diagnostic sensitivity and specificity of PE POSTN for lung cancer-related MPE were respectively 77.78% and 68.52% when the cutoff value was determined to be 53.45ng/ml. The ROC curve analysis demonstrated that PE POSTN has a high diagnostic value in MPE associated with lung cancer [area under the curve (AUC)=0.764], and the combination of PE POSTN, PE CEA, and CR can improve the diagnostic accuracy of lung cancer-related MPE (AUC=0.948). POSTN can be used as a potential marker for lung cancer-related MPE diagnosis.

Potential Clinical Value of 5-Hydroxytryptamine Receptor 3C as a Prognostic Biomarker for Lung Cancer.

Ion channels and pumps not only regulate membrane potential, ion homeostasis, and electric signaling in excitable cells but also contribute to cell proliferation, migration, apoptosis, and differentiation. Channel proteins and ion pumps can form macromolecular complexes with signaling molecules, including growth factors and cell adhesion molecules. Serotonin (5-hydroxytryptamine (5-HT)) promotes the proliferation of various cancer cell types mediated through the activation of the 5-HT receptor (HTR). Only HTR3 is a ligand-gated ion channel. However, the role of the HTR3 family of HTRs in lung cancer has not been adequately evaluated. We evaluated the relationship between the HTR3 family of HTRs and lung cancer patients' survival using Kaplan–Meier analyses and examined the expression levels of target proteins using immunohistochemistry. In this study, we found that HTR3C was amplified with high frequency in lung cancer patients, and HTR3C protein expression levels were significantly associated with lymph node metastasis and distant metastasis in lung cancer tissues. Survival analysis using the log-rank test demonstrated a decrease in disease-free survival (DFS) and overall survival (OS) rates among the high-level HTR3C expression group compared with the low-level HTR3C expression group. We also evaluated the risk factors associated with lung cancer. The univariate and multivariate analyses of DFS and OS showed that HTR3C expression was a significant predictor of patient outcomes. Taken together, these data demonstrated that HTR3C expression levels were associated with poor DFS and OS in lung cancer patients, indicating that HTR3C can serve as a useful predictive biomarker for lung cancer.

Modular signature of long non-coding RNA association networks as a prognostic biomarker in lung cancer

BackgroundIncreasing amount of long non-coding RNAs (lncRNAs) have been found involving in many biological processes and played salient roles in cancers. However, up until recently, functions of most lncRNAs in lung cancer have not been fully discovered, particularly in the co-regulated lncRNAs. Thus, this study aims to investigate roles of lncRNA modules and uncover a module-based biomarker in lung adenocarcinoma (LUAD).ResultsWe used gene expression profiles from The Cancer Genome Atlas (TCGA) to construct the lncRNA association networks, from which the highly-associated lncRNAs are connected as modules. It was found that the expression of some modules is significantly associated with patient’s survival, including module N1 (HR = 0.62, 95% CI = 0.46–0.84, p = 0.00189); N2 (HR = 0.68, CI = 0.50–0.93, p = 0.00159); N4 (HR = 0.70, CI = 0.52–0.95, p = 0.0205) and P3 (HR = 0.68, CI = 0.50–0.92, p = 0.0123). The lncRNA signature consisting of these four prognosis-related modules, a 4-modular lncRNA signature, is associated with favourable prognosis in TCGA-LUAD (HR = 0.51, CI = 0.37–0.69, p value = 2.00e−05). Afterwards, to assess the performance of the generic modular signature as a prognostic biomarker, we computed the time-dependent area under the receiver operating characteristics (AUC) of this 4-modular lncRNA signature, which showed AUC equals 68.44% on 336th day. In terms of biological functions, these modules are correlated with several cancer hallmarks and pathways, including Myc targets, E2F targets, cell cycle, inflammation/immunity-related pathways, androgen/oestrogen response, KRAS signalling, DNA repair and epithelial-mesenchymal transition (EMT).ConclusionTaken together, we identified four novel LUAD prognosis-related lncRNA modules, and assessed the performance of the 4-modular lncRNA signature being a prognostic biomarker. Functionally speaking, these modules involve in oncogenic hallmarks as well as pathways. The results unveiled the co-regulated lncRNAs in LUAD and may provide a framework for further lncRNA studies in lung cancer.

The Role of Change Rates of CYFRA21-1 and CEA in Predicting Chemotherapy Efficacy for Non-Small-Cell Lung Cancer.

Background Cytokeratin 19 fragment 21-1 (CYFRA21-1) and carcinoembryonic antigen (CEA) are effective prognostic biomarkers for lung cancer. This study investigated the predictive effects of change rates of CYFRA21-1 and CEA before and after the first cycles of chemotherapy on advanced IIIb/IIIc or IV stage non-small-cell lung cancer (NSCLC) patients. Methods Data of 103 NSCLC patients who received chemotherapy in Zhejiang Provincial People's Hospital from February 2018 to November 2020 were retrospectively analyzed. All patients received platinum doublet chemotherapy for at least 2 cycles. CYFRA21-1 and CEA levels of patients were detected before and after the first chemotherapy cycle, respectively. After the second cycle, the efficacy was evaluated, and patients were divided into the disease control (DC) and progressive disease (PD) groups. The generalized linear model (GLM) and linear trend test assessed the relationship between change rates of CYFRA21-1 and CEA levels and chemotherapeutic efficacy before and after chemotherapy. Moreover, the receiver operating characteristic (ROC) curve determined the predictive value of change rates of CYFRA21-1 and CEA on chemotherapeutic efficacy. Results After the second chemotherapeutic cycle, there were 92 patients in the DC group and 11 in the PD group. GLM and linear trend test both indicated that change rates of CYFRA21-1 and CEA were inversely correlated with chemotherapeutic efficacy for NSCLC. Change rates of CYFRA21-1 and CEA were used to predict area under the ROC curve of chemotherapeutic efficacy (0.87, 0.71-1.00), which is better than single index prediction of CYFRA21-1 (0.71, 0.49-0.94) or CEA change rate (0.85, 0.69-1.00) (p < 0.001). Conclusion Before and after chemotherapy of the first cycle for advanced NSCLC patients, combining serum CYFRA21-1 and CEA levels could increase sensitivity and specificity to predict the chemotherapeutic efficacy and guide the following therapy of advanced NSCLC patients.