Marker For Lung Cancer Research Articles

Thyroid hormones as biomarkers of lung cancer: a retrospective study

Background Thyroid hormones are key regulators of several physiological processes, including differentiation, embryonic development, proliferation, and metabolism. Several prospective studies have shown a relationship between hyperthyroidism and cancer incidence; however, since the association between thyroid hormone levels and lung cancer remains controversial, this study aimed to determine the correlation between the same. Methods We retrospectively analyzed 289 patients, who were diagnosed with lung cancer at the Huzhou Central Hospital between January 2016 and January 2021, and 238 healthy subjects. The baseline clinical data of two groups were collected. The concentrations of thyroid hormones, tumor CEA, CYF, SCC, and NSE in both the lung cancer patient and healthy volunteer groups were analyzed. Student’s t-test or Mann–Whitney test was used to compare continuous variables. A chi-square test was adopted to estimate the relationship between serum thyroid hormones level and clinical characteristics of lung cancer cases. ROC curve analyses were used to determine the characteristics of thyroid hormones for recognizing lung cancer. Results The results showed that serum thyroid stimulating hormone (TSH), total thyroxine, total triiodothyronine, and free triiodothyronine (FT3) levels were significantly decreased, while free thyroxine (FT4) levels were increased in patients with lung cancer. In addition, FT3 was identified as a potential diagnostic biomarker of stage I–IV lung cancer with the area under the curve values of 0.807. What’s more, FT3 and FT4 were used in combination with CEA and were identified as potential diagnostic biomarkers of stage 0 lung cancer (Tis) with the area under the curve values of 0.774. Conclusions Our study highlights the possibility of using thyroid hormones as innovative diagnostic markers for lung cancer.

90P Cell-free DNA as a predictive and prognostic marker in adjuvant-treated non-small cell lung cancer

90P Cell-free DNA as a predictive and prognostic marker in adjuvant-treated non-small cell lung cancer

Advances in exosome research in the management of lung cancer.

Lung cancer is one of the most common malignant tumors, and its death rate is much higher than that of colon, kidney, breast, and prostate cancers, and its 5-year survival rate is only 18%. Lung cancer has no specific clinical symptoms in its early stages and lacks effective detection, making early detection difficult. The survival rate for advanced lung cancer is meager, with a median survival of only 12 months for stage IIIB/IV non-small cell lung cancer treated with platinumbased chemotherapy. Exosomes could provide vital information for the early diagnosis of lung cancer and have the potential to become a tumor marker for lung cancer. In addition, scientists have proposed encouraging ways to treat lung cancer by loading drugs, proteins, microRNAs, and siRNAs into exosomes. Therefore, studying lung cancer exosomes and exosomal nano drugs will provide new ideas and approaches for the diagnosis and treatment of lung cancer. This paper reviews the progress of research on the biological functions of exosomes and exosomal nanomedicines and their applications in clinical practice.

A new prognostic marker in small cell lung cancer: red cell distribution width ratio of hemoglobin

Aim: The ratio of hemoglobin (Hb) to red cell distribution width (RDW) (HRR) has been defined as an effective prognostic factor in various cancer types. The aim of this study is to investigate the prognostic role of HRR value in small cell lung cancer (SCLC). Material and Method: A total of 1039 patients diagnosed with SCLC between 2010-2021 were included in the study. After exclusion of 199 patients without positron emission tomography-computerized tomography (PET-CT), age, gender, additional disease histories, smoking history, pathological stages, survival status, disease progression times, treatments applied, first hemoglobin obtained after diagnosis, red cell distribution width and ratios, and other laboratory parameters of 840 patients were recorded. The log-rank test and the Cox proportional hazards model were used to identify predictors of mortality. Results: A total of 840 patients were included in the study. The median overall survival (OS) and the progression-free survival (PS) times of the patients were 9 months, and 7 months, respectively. The cut-off value for HRR was determined 0.580 (sensitivity 78.73%, specificity 37.88%). In this study, each one-unit increase in HRR reduces death and survival by 1.6 times detected, and it was revealed that HRR had a statistically significant effect on OS and PS. When the patients were divided into two as limited and extensive disease, there was a statistically significant difference between the groups in terms of OS (12-6 months) and PS (10-6 months), but no significant difference was found in terms of HRR between these two groups. Conclusion: HRR is an easily accessible, inexpensive parameter that can be used as a prognostic marker in patients with SCLC.

Identification of IRAK1BP1 as a candidate prognostic factor in lung adenocarcinoma.

Lung cancer is one of the major causes of cancer-related mortality worldwide. High-throughput RNA sequencing (RNA-seq) of surgically removed tumors has been used to identify new biomarkers of lung cancer; however, contamination by non-tumor cells in the tumor microenvironment significantly interferes with the search for novel biomarkers. Tumor organoids, as a pre-clinical cancer model, exhibit similar molecular characteristics with tumor samples while minimizing the interference from other cells. Here we analyzed six RNA-seq datasets collected from different organoid models, in which cells with oncogenic mutations were reprogrammed to mimic lung adenocarcinoma (LUAD) tumorigenesis. We uncovered 9 LUAD-specific biomarker genes by integrating transcriptomic data from multiple sources, and identified IRAK1BP1 as a novel predictor of LUAD disease outcome. Validation with RNA-seq and microarray data collected from multiple patient cohorts, as well as patient-derived xenograft (PDX) and lung cancer cell line models confirmed that IRAK1BP1 expression was significantly lower in tumor cells, and had no correlation with known markers oflung cancer prognosis. In addition, loss of IRAK1BP1 correlated with the group of LUAD patients with worse survival; and gene-set enrichment analysis using tumor and cell line data implicated that high IRAK1BP1 expression was associated with suppression of oncogenic pathways. In conclusion, we demonstrate that IRAK1BP1 is a promising biomarker of LUAD prognosis.

Interleukin 8 in plasma is an efficacy marker for advanced non-small cell lung cancer treated with hypofractionated radiotherapy and PD-1 blockade.

Programmed death-1 (PD-1) blockade promotes combination therapy in advanced non-small cell lung cancer (NSCLC), hypofractionated radiotherapy (HFRT) and chemotherapy combined with immunotherapy improves the outcome of prognosis in advanced NSCLC, while effective biomarkers to follow prognostic efficacy are still to be found. We enrolled 44 NSCLC patients with HFRT combined with PD-1 blockade, 13 patients with chemotherapy combined with immunotherapy, additionally collected tissue samples from 8 patients with earlystage NSCLC without therapy, and peripheral whole blood from 16 healthy donors, detected the expression differences of cytokines Interleukin 6 (IL-6), Interleukin 8 (IL-8) and Interleukin 17A (IL-17A) in the peripheral plasma and tissues by flow cytometry, immunofluorescence, and real-time fluorescence quantitative PCR. Cultured peripheral blood mononuclear cell (PBMC) and tumor-infiltrating T cells with recombinant human IL-8 in vitro to observe the changes of immune memory T cell subtypes and apoptosis. Our results show that IL-6, IL-8, and IL-17A are highly expressed in advanced NSCLC, high levels of IL-8 are significantly associated with poor prognosis in advanced NSCLC patients treated with HFRT+PD1 blockade, high circulating IL-8 in NSCLC increased apoptosis of effector memory RA (TemRA; CD45RA+CCR7-) T cell subsets and CD8+ T cell subsets in tissues, resulting in decreased peripheral TemRA and stem cell-like memory T cells (TSCM: CD45RA +CCR7 + CD95 +) in tissue. We suggest that IL-8 can impair immune memory function in NSCLC. It is a useful biomarker to evaluate the efficacy of HFRT+PD1 blockade in advanced NSCLC. Further exploration of easily available plasma biomarkers for personalized treatment of NSCLC is required.

Circular RNAs as biomarkers for lung cancer

Lung cancer is the leading cause of death and morbidity from malignant neoplasms worldwide, and its poor prognosis places a heavy burden on patients. A large percentage of lung cancer cases are associated with smoking. A significant number of non-smokers also develop the disease, suggesting an epigenetic and genetic mechanism for the development of lung cancer. The current situation with the diagnosis and treatment of lung cancer remains grim, and effective therapeutic targets and molecular markers are urgently needed. Circular RNAs (circRNAs) are covalently closed non-coding RNAs that have received much attention due to their biological properties such as conservatism, stability, and tissue specificity. Many studies have shown that circRNAs are involved in the regulation of lung cancer through various mechanisms, such as microRNA adsorption, and play an important role in the early diagnosis, treatment, and prognosis of lung cancer. In recent years, it has become increasingly clear that circRNAs are involved in the proliferation, migration, and invasion of lung cancer cells. Differentially expressed circRNAs can be used as non-invasive diagnostic and prognostic markers of lung cancer. This article summarizes the current advances of circRNAs in the diagnosis, treatment and prognosis of lung cancer.

Diagnostic value of tumor-associated autoantibodies panel in combination with traditional tumor markers for lung cancer.

The diagnostic value of 7 tumor-associated autoantibodies (AABs) including p53, PGP9.5, SOX2, GAGE7, GBU4-5, MEGEA1, and CAGE for the detection of lung cancer has shown inconsistency in several studies. This study aimed to confirm the diagnostic value of 7AABs and to explore whether the diagnostic value would be improved by combining them with 7 traditional tumor-associated antigens (CEA, NSE, CA125, SCC, CA15-3, pro-GRP, and CYFRA21-1) in clinical settings. The plasma levels of 7-AABs were detected by enzyme-linked immunosorbent assay (ELISA) in 533 lung cancer cases and 454 controls. The 7 tumor antigens (7-TAs) were measured by Electrochemiluminescence immunoassay with Cobas 6000 (Roche, Basel, Switzerland). The positive rate of 7-AABs in the lung cancer group (64.00%) was significantly higher than that of healthy controls (47.90%). The 7-AABs panel was able to discriminate lung cancer from controls with a specificity of 51.50%. After combining the 7-AABs with 7-TAs, the sensitivity showed a significantly enhancement compared with 7AABs panel alone (92.09% vs 63.21%). In patients with resectable lung cancer, the combination of 7-AABs and 7-TAs improved the sensitivity from 63.52% to 97.42. In conclusion, our study found that the diagnostic value of 7-AABs was enhanced when combined with 7-TAs. This combined panel could be used as promising biomarker to detect resectable lung cancer in clinical settings.

Prognostic significance of tumor-associated macrophages polarization markers in lung cancer: a pooled analysis of 5105 patients.

The prognostic significance of tumor-associated macrophages (TAMs) in patients with lung cancer (LCa) remains controversial. We therefore conducted the present study to systematically evaluate the role of different TAMs markers and histologic locations on the prognosis of LCa. Searches of Web of Science, PubMed, and EMBASE databases were performed up to 28 February 2022. The pooled analysis was conducted in random-effect or fixed-effects model with hazard risk (HR) and 95% confidence interval (CI) for survival data including overall survival (OS), and disease-free survival (DFS) from raw or adjusted measures, according to different TAMs markers and histologic locations. Including a total of 5105 patients from 30 eligible studies, the results indicated that the total count of CD68+ TAMs was negatively associated with OS and DFS, which was also observed in the relationship of CD68+ or CD204+ TAMs in tumor stroma (TS) with OS and DFS (all P<0.05). Conversely, higher CD68+ TAMs density in tumor nest (TN) or TN/TS ratio of CD68+ TAMs predicted better OS (all P<0.05). Similarly, higher HLA-DR+ TAMs density was correlated with better OS in TN and TS (all P<0.05). Besides, neither nest CD163+ TAM density nor stromal CD163+ TAM density was a prognostic factor in LCa patients (all P>0.05). Our study indicated that different TAMs markers and histologic locations could bring about different prognostic effects in LCa patients. Great understanding of the infiltration modes of TAMs may contribute to improve outcomes of LCa patients.

The Value of Circulating Tumor Cells and Tumor Markers Detection in Lung Cancer Diagnosis.

Circulating tumor cells are complete tumor cells with multi-scale analysis values that present a high potential for lung cancer diagnosis. To enhance the accuracy of lung cancer diagnosis, we detected circulating tumor cells by the innovated conical micro filter integrated microfluidic system. We recruited 45 subjects of study, including 22 lung cancer patients, 2 precancerous patients, the control group including 14 healthy participants, and 7 patients with lung benign lesions in this prospective study. We calculated the area under the receiver operating characteristic curve of circulating tumor cells, cytokeratin19 fragment, carcinoma embryonic antigen, squamous cell carcinoma, neuron-specific enolase, and their combination, respectively, while compared the circulating tumor cells levels between vein blood and arterial blood. A conical shape filter embedded in a microfluidic chip was used to improve the detection capability of circulating tumor cells. The study indicated that the sensitivity, specificity, positive predictive value, and negative predictive value of circulating tumor cells detection were 81.8%, 90.5%, 90.0%, and 82.6%, respectively. The circulating tumor cells level of lung cancer patient was significantly higher than that of the control group (P < .05). The area under the curve of circulating tumor cells, cytokeratin19 fragment, carcinoma embryonic antigen, squamous cell carcinoma, and neuron-specific enolase alone was 0.838, 0.760, 0.705, 0.614, and 0.636, respectively. The combination area under the curve of the 4 tumor markers (cytokeratin19 fragment, carcinoma embryonic antigen, squamous cell carcinoma, and neuron-specific enolase) was 0.805 less than that of circulating tumor cells alone. Together, the total area under the curve of circulating tumor cell and the 4 tumor markers were 0.847, showing the highest area under the curve value among all biomarkers. In addition, this study found that there was no significant difference in positive rate of circulating tumor cell between arterial and venous blood samples. The circulating tumor cells detection technology by conical micro filter integrated microfluidic could be used for lung cancer diagnosis with high sensitivity and specificity. Complementary combination of circulating tumor cells and conventional 4 lung cancer markers could enhance the clinical application accuracy. Venous blood should be used as a routine sample for circulating tumor cells detections.

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.

Evaluation of TET Family Gene Expression and 5-Hydroxymethylcytosine as Potential Epigenetic Markers in Non-small Cell Lung Cancer.

DNA methylation is the most studied epigenetic modification in cancer. Ten-eleven translocation enzymes (TET) catalyze the oxidation of 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC) in the DNA. In the current research, we aimed to evaluate the role of 5-hmC and TET enzymes in non-small cell lung cancer (NSCLC) patients and their possible association with outcomes. ELISA was used to measure the 5-hmC levels in genomic DNA and qRT-PCR was used to evaluate TET1, TET2, and TET3 mRNAs expression levels in NSCLC tissues and their paired normal controls. The levels of 5-hmC were significantly lower in NSCLC tissues than in normal tissues, with a mean ±SD of 0.28±0.37 vs. 1.84±0.58, respectively (t=22.77, p<0.0001), and this reduction was correlated with adverse clinical features. In addition, all TET genes were significantly down-regulated in NSCLC tissues in comparison to their matched normal tissues. The mean±SD level of TET1-mRNA was 38.48±16.38 in NSCLC vs. 80.65±11.25 in normal tissues (t=21.33, p<0.0001), TET2-mRNA level in NSCLC was 5.25±2.78 vs. 9.52±1.01 in normal tissues (t=14.48, p<0.0001), and TET3-mRNA level in NSCLC was 5.21±2.8 vs. 9.51±0.86 in normal tissues (t=14.75, p<0.0001). Downregulation of TET genes was correlated with poor clinical features. 5-HmC levels as well as TET1, TET2, and TET3 mRNA levels were reduced in NSCLC tissues. The reduced levels of 5-hmC and TET mRNAs were associated with adverse clinical features, suggesting that the level of 5-hmC may serve as a valuable prognostic biomarker for NSCLC.

Correlation of Short Leukocyte Telomeres and Oxidative Stress with the Presence and Severity of Lung Cancer Explored by Principal Component Analysis

Lung cancer (LC) is the second most common malignancy and leading cause of cancer death. The potential “culprit” for local and systemic telomere shortening in LC patients is oxidative stress. We investigated the correlation between the peripheral blood leukocyte (PBL) telomere length (TL) and the presence/severity of LC and oxidative stress, and its usefulness as LC diagnostic marker. PBL TL was measured in 89 LC patients and 83 healthy subjects using the modified Cawthon RTq-PCR method. The relative PBL TL, found to be a potential diagnostic marker for LC with very good accuracy (P &lt; 0.001), was significantly shorter in patients compared to the control group (CG) (P &lt; 0.001). Significantly shorter telomeres were found in patients with LC TNM stage IV than in patients with stages I-III (P = 0.014), in patients without therapy compared to those on therapy (P = 0.008), and in patients with partial response and stable/progressive disease compared to those with complete response (P = 0.039). The total oxidant status (TOS), advanced oxidation protein products (AOPP), prooxidant-antioxidant balance (PAB) and C-reactive protein (CRP) were significantly higher in patients compared to CG (P &lt; 0.001) and correlated negatively with TL in both patients and CG (P &lt; 0.001). PCA showed a relation between PAB and TL, and between the EGFR status and TL. Oxidative stress and PBL telomere shortening are probably associated with LC development and progression.

Value of human epididymis secretory protein 4 in differentiating malignant from benign pleural effusion: an analysis of two cohorts.

Lung cancer is the most common cause of malignant pleural effusion (MPE). Serum human epididymis secretory protein 4 (HE4) is a useful diagnostic marker for lung cancer. This study aimed to evaluate the diagnostic accuracy of pleural fluid HE4 for MPE. A prospective, double-blind diagnostic test accuracy study. Patients with undiagnosed pleural effusion were enrolled in two cohorts (Hohhot and Changshu). Electrochemiluminescence immunoassay was used to detect pleural fluid HE4. The diagnostic accuracy of HE4 was evaluated by a receiver operating characteristic (ROC) curve, and the net benefit of HE4 was assessed by a decision curve analysis (DCA). A total of 66 MPEs and 86 benign pleural effusions (BPEs) were enrolled in the Hohhot cohort. In the Changshu cohort, 26 MPEs and 32 BPEs were enrolled. In both cohorts, MPEs had significantly higher pleural fluid HE4 than BPEs. The area under the ROC curve (AUC) of HE4 was 0.73 (95% CI: 0.64-0.81) in the Hohhot cohort and 0.79 (95% CI: 0.67-0.91) in the Changshu cohort. At a threshold of 1300 pmol/L, HE4 had sensitivities of 0.44 (95% CI: 0.33-0.56) in the Hohhot cohort and 0.54 (95% CI: 0.35-0.73) in the Changshu cohort. The corresponding specificities were 0.90 (95% CI: 0.83-0.95) in the Hohhot cohort and 0.94 (95% CI: 0.84-1.00) in the Changshu cohort. In subgroup analyses, HE4 had an AUC (95% CI) of 0.78 (0.71-0.85) in exudates and an AUC of 0.69 (0.57-0.81) in patients with negative effusion cytology. The DCA revealed that HE4 determination had a net benefit in both cohorts. Pleural fluid HE4 has moderate diagnostic accuracy for MPE and has net benefit in pleural effusion patients with unknown etiology.

基于双层探测器光谱CT探讨肺癌的影像学特征及血清肿瘤标志物的相关性

基于双层探测器光谱CT探讨肺癌的影像学特征及血清肿瘤标志物的相关性

Recent progress of biosensors for the detection of lung cancer markers.

Lung cancer is one of the most common cancers worldwide and the leading cause of death. Early screening of lung cancer is exceptionally essential for later treatment. Abnormal lung cancer tumor markers are validated to assess their diagnostic utility in non-small cell lung cancer (NSCLC) patients. Therefore, tumor markers can be identified in the early stage of lung cancer through biosensor technology and timely diagnosis. This review discusses cutting-edge methods for detecting various types of lung cancer tumor markers using multiple biosensors. The biosensors working at the molecular level are mainly introduced, which can be divided into three categories according to the types of markers: DNA biosensors, RNA biosensors, and protein biosensors. This review focuses on critical electrochemical methods such as electrochemical impedance spectroscopy (EIS), field-effect transistors (FET), cyclic voltammetry (CV), necessary optical sensors such as surface enhancement Raman spectroscopy (SERS), surface-plasmon resonance (SPR), fluorescence methods, and some novel sensing platforms such as biological nanopore and solid-state nanopore sensors and these sensors detect lung cancer tumor markers, such as microRNA (miRNA), DNA mutations (EGFR, KRAS and p53), DNA methylation, circulating tumor DNA (ctDNA), cytokeratin fragment 21-1 (CYFRA21-1), carcinoembryonic antigen (CEA), matrix metallopeptidase 9 (MMP-9), and vascular endothelial growth factor (VEGF). The advantages and disadvantages of different methods are summarized and prospected on this basis, which provides important insights for developing pioneering optoelectronic biosensors for the early diagnosis of lung cancer.

AURKA Identified as Potential Lung Cancer Marker through Comprehensive Bioinformatic Analysis and Experimental Verification.

Non-small-cell lung cancer (NSCLC) is a malignancy with high overall morbidity and mortality due to a lack of reliable methods for early diagnosis and successful treatment of the condition. We identified genes that would be valuable for the diagnosis and prognosis of lung cancer. Common DEGs (DEGs) in three GEO datasets were selected for KEGG and GO enrichment analysis. A protein-protein interaction (PPI) network was constructed using the STRING database, and molecular complex detection (MCODE) identified hub genes. Gene expression profiling interactive analysis (GEPIA) and the Kaplan-Meier method analyzed hub genes expression and prognostic value. Quantitative PCR and western blotting were used to test for differences in hub gene expression in multiple cell lines. The CCK-8 assay was used to determine the IC50 of the AURKA inhibitor CCT137690 in H1993 cells. Transwell and clonogenic assays validated the function of AURKA in lung cancer, and cell cycle experiments explored its possible mechanism of action. Overall, 239 DEGs were identified from three datasets. AURKA, BIRC5, CCNB1, DLGAP5, KIF11, and KIF15 had shown great potential for lung cancer diagnosis and prognosis. In vitro experiments suggested that AURKA significantly influenced the proliferation and migration of lung cancer cells and activities related to the dysregulation of the cell cycle. AURKA, BIRC5, CCNB1, DLGAP5, KIF11, and KIF15 may be critical genes that influence the occurrence, development, and prognosis of NSCLC. AURKA significantly affects the proliferation and migration of lung cancer cells by disrupting the cell cycle.

Pretreatment Platelet Count is a Prognostic Marker in Lung Cancer: A Danish Registry-based Cohort Study

BackgroundThrombocytosis has been associated with a poor prognosis in a wide range of malignancies. However, the results have been conflicting for lung cancer. Therefore, we evaluated the prognostic value of platelet count in a large cohort of lung cancer patients. Patients and MethodsAll lung cancer patients diagnosed in The Central Denmark Region from 2009 to 2018 were included in the study. Data from the Danish Lung Cancer Registry were combined with data from the clinical laboratory information system on pretreatment platelet count. Platelet count was defined as low, normal, or high based on being below, within, or above the reference intervals. The prognostic value of platelet count was assessed by the Cox proportional hazard model. C-statistics were conducted to investigate if the platelet count added additional prognostic value to existing prognostic markers. ResultsTotally, 6,758 patients with non–small-cell lung cancer (NSCLC) and 1150 patients with small-cell lung cancer (SCLC) were included. Low and high platelet count were significantly associated with decreased overall survival (OS) in NSCLC patients (low: adjusted hazard ratio (HR)=1.75 (95% confidence interval [CI]: 1.49-2.06); high: adjusted HR=1.24 (95% CI: 1.16-1.33)). In SCLC patients, only low platelet count was significantly associated with decreased OS (adjusted HR = 2.71 [95% CI: 2.02-3.65]). C-statistics showed that the prognostic models were significantly improved by the addition of platelet count for both NSCLC and SCLC patients (P < .0001). ConclusionLow and high platelet count were adverse prognostic factors in NSCLC patients, while only low platelet count was a prognostic marker in SCLC patients.

CircTAB2 inhibits lung cancer proliferation, migration and invasion by sponging miR-3142 to upregulate GLIS2.

Circular RNAs (circRNAs) are a specialized circular structure, are deregulated in cancers and play essential roles in biological processes involved in tumor progression. However, the mechanism by which circRNAs affect lung tumorigenesis and progression remains largely unexplored. To investigate the role of circRNA in lung cancer, circRNA expression profile was screened by bioinformatics analysis. The levels of circTAB2, miR-3142, and GLIS family zinc finger 2 (GLIS2) were measured by quantitate real-time (qRT-PCR) or western blot. Cell proliferation, apoptosis, migration and invasion were detected by EdU, flow cytometry, and transwell assays, respectively. Bioinformatics, western blot, RIP, pull down, dual luciferase reporter and rescue experiments were used to verify the direct relationship between miR-3142 and circTAB2 or GLIS2. The xenograft assays were used to assess the role of circTAB2 in vivo.CircTAB2 exhibited low expression in cancer tissues. Gain and loss-of-function assays indicated that circTAB2 could inhibit cell proliferation, migration and invasion. Functional studies revealed that circTAB2 acted as a miRNA sponge, directly interacted with miR-3142 and consequently regulated GLIS2 /AKT. Taken together, circTAB2 serves as an inhibitory role in lung cancer through a novel circTAB2 /miR-3142 /GLIS2 /AKT pathway and could be exploited a novel marker in lung cancer.

CPSF4 promotes tumor-initiating phenotype by enhancing VEGF/NRP2/TAZ signaling in lung cancer.

Lung cancer is the leading cause of malignant tumor-related deaths worldwide. The presence of tumor-initiating cells in lung cancer leads to tumor recurrence, metastasis, and resistance to conventional treatment. Cleavage and polyadenylation specificity factor 4 (CPSF4) activation in tumor cells contributes to the poor prognosis of lung cancer. However, the precise biological functions and molecular mechanisms of CPSF4 in the regulation of tumor-initiating cells remain unclear. We demonstrated that CPSF4 promotes tumor-initiating phenotype and confers chemoresistance to paclitaxel both in vitro and in vivo. Mechanistically, we showed that CPSF4 binds to the promoters of vascular endothelial growth factor (VEGF) and neuropilin-2 (NRP2) and activated their transcription. In addition, we showed that CPSF4/VEGF/NRP2-mediated tumor-initiating phenotype and chemoresistance through TAZ induction. Furthermore, analysis of clinical data revealed that lung cancer patients with high CPSF4 expression exhibit high expression levels of VEGF, NRP2, and TAZ and that expression of these proteins are positively correlated with poor prognosis. Importantly, selective inhibition of VEGF, NRP2, or TAZ markedly suppressed CPSF4-mediated tumor-initiating phenotype and chemoresistance. Our findings reveal the mechanism of CPSF4 modulating tumor-initiating phenotype and chemoresistance in lung cancer and indicate that the CPSF4-VEGF-NRP2-TAZ signaling pathway may be a prognosis marker and therapeutic target in lung cancer.