Independent Prognostic Factor In Non-small Cell Lung Cancer Research Articles

Efficacy and safety of time-of-day infusion of pemetrexed plus platinum and paclitaxel plus platinum for patients with advanced non-small cell lung cancer: A retrospective study.

e20557 Background: Retrospective studies suggest that administering chemotherapy infusions in the morning can enhance treatment efficacy and mitigate side effects in non-small cell lung cancer (NSCLC) patients. However, the effectiveness of chronotherapy using pemetrexed plus platinum (AP) and paclitaxel plus platinum (TP) in advanced NSCLC chemotherapy remains unexplored. This study aims to evaluate the impact of AP and TP chrono-chemotherapy (CCT) on treatment response and adverse events in advanced NSCLC patients. Methods: We retrospectively analyzed 78 advanced NSCLC patients treated with AP (AP cohort) and 50 advanced NSCLC patients treated with TP (TP cohort) at Guangdong Second Provincial General Hospital from 2018 to 2021. Based on previous research, we classified patients who received chemotherapy infusions more than twice after 2:00 PM as the afternoon (PM) group, while the rest were categorized as the morning (AM) group. Treatment response was evaluated using the Response Evaluation Criteria in Solid Tumors Criteria V.1.1. The primary endpoint was progression-free survival (PFS). All adverse events were identified and graded according to the National Cancer Institute-Common Terminology Criteria for Adverse Events version 5.0. Results: In the AP cohort, the AM group exhibited a longer PFS compared to the PM group (AM vs. PM, n = 26 vs. n = 52, 43.0 vs. 13.0 months, p = 0.001). However, no significant difference was observed in PFS in the TP cohort (AM vs. PM, n = 23 vs. n = 27, 11.0 vs. 22.0 months, p = 0.501). Subsequent subgroup analysis in the AP cohort favored the AM group across all major subgroups for PFS treatment effect. In contrast, the TP cohort subgroups showed a PFS benefit only in the smoking patients of the PM group. Furthermore, the analysis of adverse reactions revealed similar incidences of any treatment emergent adverse events (TEAE) in both AP and TP cohorts (AM vs. PM, 92.3% vs. 86.5% in AP cohort and 95.7% vs. 100.0% in TP cohort), and grade 3 TEAEs (AM vs. PM, 34.6% vs. 21.2% in AP cohort and 39.1% vs. 29.63% in TP cohort). The most common adverse events were anemia (73.1%), leukopenia (57.7%), and elevated ALT (46.2%) in AP cohort and anemia (100%), leukopenia (65.2%), and hypoalbuminemia (47.8%) in TP cohort. Univariate and multivariate analyses indicated that afternoon infusion of AP chemotherapy (p = 0.009) was an independent prognostic factor for NSCLC. Conclusions: AP treatment administered in the morning may enhance PFS in advanced NSCLC, while TP remains unaffected. This suggests that CCT could potentially enhance the efficacy of individualized chemotherapy in advanced NSCLC.

Detection of PD‑L1 expression and epithelial‑mesenchymal transition of circulating tumor cells in non‑small cell lung cancer.

The present study aimed to assess the roles of peripheral circulating tumor cell (CTC) count, CTC subtypes and programmed death ligand 1 (PD-L1) expression in the clinical staging and prognosis of patients with non-small cell lung cancer (NSCLC). A total of 100 patients with NSCLC with available tumor tissues were enrolled in the present study, and 7.5 ml peripheral blood was collected. Patients were divided into PD-L1-positive and PD-L1-negative groups according to PD-L1 immunohistochemical staining. Peripheral blood samples from both groups were analyzed to determine the CTC count, epithelial-type CTCs (E-CTCs), mesenchymal-type CTCs (M-CTCs) and PD-L1 expression. Clinical data were collected, and patients were followed up for a maximum of 36 months, with patient death as the endpoint event. Patients with PD-L1-positive tumors had a worse prognosis compared with those with PD-L1-negative tumors (P=0.045). The PD-L1-positive group exhibited significantly higher numbers of CTCs and M-CTCs compared with the PD-L1-negative group (P≤0.05). However, the number of E-CTCs did not differ significantly between the two groups (P>0.05). PD-L1-positive patients with higher CTC and M-CTC counts had relatively poorer prognoses (P≤0.05), while the number of E-CTCs had no significant effect on prognosis (P>0.05). Compared with the early-stage NSCLC group, the late-stage NSCLC group exhibited a significant increase in the CTC count (P≤0.05), while E-CTC and M-CTC counts did not significantly differ between the two groups (P>0.05). The PD-L1-positive group exhibited a significant increase in the number of PD-L1+ CTCs and PD-L1+ M-CTCs compared with the PD-L1-negative group (P≤0.05), while PD-L1+ E-CTC counts did not differ significantly between the two groups (P>0.05). The PD-L1-positive patients with a higher number of PD-L1+ CTCs and PD-L1+ M-CTCs had relatively poorer prognoses (P≤0.05), while the PD-L1+ E-CTC count had no significant effect on prognosis (P>0.05). Compared with the early-stage NSCLC group, the late-stage NSCLC group exhibited a significant increase in the number of PD-L1+ CTCs and PD-L1+ M-CTCs (P≤0.05), while PD-L1+ E-CTC counts did not significantly differ between the two groups (P>0.05). Based on univariate and multivariate analyses, the number of PD-L1+ M-CTCs was identified as an independent prognostic factor for NSCLC. In conclusion, the presence of CTCs in peripheral blood, particularly PD-L1+ M-CTC subtype, indicated poorer clinical staging and prognosis in patients with NSCLC. These findings suggested that CTCs, specifically the PD-L1+ M-CTC subtype, could serve as a monitoring indicator for the clinical staging and prognosis of patients with NSCLC.

Trajectory patterns and cumulative burden of CEA during follow-up with non-small cell lung cancer outcomes: A retrospective longitudinal cohort study.

Previous studies of non-small cell lung cancer (NSCLC) focused on CEA measured at a single time point, ignoring serial CEA measurements. This retrospective cohort included 2959 patients underwent surgery for stage I-III NSCLC. CEA trajectory patterns and long-term cumulative CEA burden were evaluated using the latent class growth mixture model. Four CEA trajectory groups were identified, named as low-stable, decreasing, early-rising and later-rising. Compared with the low-stable group, the adjusted hazard ratios associated with death were 1.27, 4.50, and 3.68 for the other groups. Cumulative CEA burden were positively associated with the risk of death in patients not belonging to the low-stable group. The 5-year overall survival (OS) rates decreased from 62.3% to 33.0% for the first and fourth quantile groups of cumulative CEA burden. Jointly, patients with decreasing CEA trajectory could be further divided into the decreasing & low and decreasing & high group, with 5-year OS rates to be 77.9% and 47.1%. Patients with rising CEA trajectory and high cumulative CEA were found to be more likely to develop bone metastasis. Longitudinal trajectory patterns and long-term cumulative burden of CEA were independent prognostic factors of NSCLC. We recommend CEA in postoperative surveillance of NSCLC.

Single-cell transcriptomic sequencing data reveal aberrant DNA methylation in SMAD3 promoter region in tumor-associated fibroblasts affecting molecular mechanism of radiosensitivity in non-small cell lung cancer

ObjectiveNon-small cell lung cancer (NSCLC) often exhibits resistance to radiotherapy, posing significant treatment challenges. This study investigates the role of SMAD3 in NSCLC, focusing on its potential in influencing radiosensitivity via the ITGA6/PI3K/Akt pathway.MethodsThe study utilized gene expression data from the GEO database to identify differentially expressed genes related to radiotherapy resistance in NSCLC. Using the GSE37745 dataset, prognostic genes were identified through Cox regression and survival analysis. Functional roles of target genes were explored using Gene Set Enrichment Analysis (GSEA) and co-expression analyses. Gene promoter methylation levels were assessed using databases like UALCAN, DNMIVD, and UCSC Xena, while the TISCH database provided insights into the correlation between target genes and CAFs. Experiments included RT-qPCR, Western blot, and immunohistochemistry on NSCLC patient samples, in vitro studies on isolated CAFs cells, and in vivo nude mouse tumor models.ResultsFifteen key genes associated with radiotherapy resistance in NSCLC cells were identified. SMAD3 was recognized as an independent prognostic factor for NSCLC, linked to poor patient outcomes. High expression of SMAD3 was correlated with low DNA methylation in its promoter region and was enriched in CAFs. In vitro and in vivo experiments confirmed that SMAD3 promotes radiotherapy resistance by activating the ITGA6/PI3K/Akt signaling pathway.ConclusionHigh expression of SMAD3 in NSCLC tissues, cells, and CAFs is closely associated with poor prognosis and increased radiotherapy resistance. SMAD3 is likely to enhance radiotherapy resistance in NSCLC cells by activating the ITGA6/PI3K/Akt signaling pathway.

Correlation Analysis of KCNQ1 Gene Polymorphism with Blood Indexes and Prognosis of Non-Small Cell Lung Cancer.

This study was conducted to investigate the correlation between KCNQ1 rs2237895 A/C gene polymorphism and blood indexes and prognosis in non-small cell lung cancer (NSCLC). A total of 260 NSCLC patients were selected and classified into stage I - II (n = 109) and stage III - IV (n = 151) according to by American Joint Committee on Cancer Staging Manual. A control group was established with another 92 healthy subjects. The genotype distribution of rs2237895 was analyzed in all subjects. 2 analysis or Fisher's test was employed to analyze the association between genotype and allele distribution frequencies with carcinoembryonic antigen (CEA), squamous cell carcinoma antigen, and cytokeratin fragment 19 (CyfrA 21-1). Overall survival was compared by genotype stratification using Kaplan-Meier analysis. Univariate and multivariate Cox risk regression analyses were used to determine the prognostic value of allele C in NSCLC. AC/CC genotypes in NSCLC patients were associated with gender, hypertension, smoking, clinical TNM stage, lymph node metastasis, and distant metastasis. C allele was associated with higher risk levels of serum tumor markers. Patients with allele C (AC + CC) had lower overall survival than patients with genotype AA. Finally, clinical stage, lymph node metastasis, higher CEA and CyfrA 21-1 serum levels, and rs2237895 A/C gene poly-morphism were independent prognostic factors of NSCLC. rs2237895 A/C polymorphism of the KCNQ1 gene can be a prognostic predictor in patients with surgically treated NSCLC.

Carbonic Anhydrase 4 Serves as A Novel Prognostic Biomarker and Therapeutic Target for Non-Small Cell Lung Cancer: A Study Based on TCGA Samples.

Carbonic anhydrase 4 (CA4) is a member of a large family of zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide and was found to have low expression in non-small cell lung cancer (NSCLC). However, the specific role of CA4 in NSCLC and the underlying mechanisms remain unknown. The bioinformatic analysis on lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) datasets downloaded from The Cancer Genome Atlas (TCGA) database was performed. We found that CA4 expression was lower in tumors than that in normal tissues, which were verified by Real-time PCR. Lower CA4 levels were significantly associated with higher T stages in LUAD and LUSC cohorts. Multivariate analysis showed that CA4 is an independent prognostic factor for NSCLC. Furthermore, the expression of CA4 also correlated with immune infiltration and drug sensitivity. Ectopic expression of CA4 decreased NSCLC cell proliferation in vitro by CCK-8 assay. CA4 caused G0/G1 cell cycle arrest by cell experiments. Mechanistic studies found that CA affects the cell cycle and inhibits cell proliferation by downregulating the expression of CDK2. The present findings highlight the role of CA4 in NSCLC and identify CA4 as a potential novel diagnostic and prognostic biomarker for the treatment of NSCLC.

Populations particulières : patients de performance status 2 ou plus: Special populations: patients with performance status 2 or higher

Performance status (PS) is a measure of the patient’s overall condition. Karnofsky and ECOG (Eastern Cooperative Oncology Group) are the most widely used scales. A three-point conversion scale allows a strong correlation between both scores: ECOG 0-1 = Karnofsky 100-80 %, ECOG 2 = Karnofsky 60-70 %, ECOG 3-4 = Karnofsky 50-10 %. Numerous factors, whether linked to cancer or to comorbidities, can affect PS. PS remains a major independent prognostic factor in NSCLC (non small cell lung cancer) and SCLC (small cell lung cancer), despite its flawed reproducibility and the heterogeneity of cancer patients with poor PS. As a matter of fact, PS should be regarded as a stratification factor in research. All guidelines take PS into account as a therapeutic decision making tool, especially in the case of chemotherapy for metastatic NSCLC. Targeted therapy should be considered in case of metastatic disease with molecular targets regardless of PS, for its high effectiveness and good safety profile. Data regarding immunotherapy are rather sketchy. Tolerance seems to be fine. Findings regarding efficacy warrant careful selection of patients who might benefit from this therapy. In light of the European Medicines Agency call, let us build studies dedicated to patients as frail as they come and enroll them in clinical trials in such a way that they benefit, among others, from therapeutic advances. In order to apply clinical research findings to the general population, specific groups of patients should be more involved.1877-1203/© 2023 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Overexpression of Bruton Tyrosine Kinase Inhibits the Proliferation, Migration, and Invasion of Non-Small Cell Lung Cancer Cells.

Lung cancer is one of the most lethal malignant tumors in the world. Non-small cell lung cancer (NSCLC) is the most common pathological subtype. However, the molecular mechanism of NSCLC progress is still unclear. We extracted the expression data of the Bruton's tyrosine kinase (BTK) gene in NSCLC tissues from the TCGA database. The results of paired t-test showed that the BTK gene was significantly underexpressed in NSCLC tissues. To further verify the above results, we detected the expression of the BTK gene in NSCLC cell lines A549, H1299, and H1650 at the RNA and protein levels by real-time fluorescent quantitative polymerase chain reaction and Western Blot analysis, respectively. The results showed that BTK was low expressed in NSCLC tissues and cells. More importantly, the expression of the BTK gene is also significantly related to the patient's age, gender, tumor range (T), lymph node invasion (N), tumor stage, and prognosis, and its expression level gradually decreases with the progress of the disease. It is speculated that BTK may be an independent prognostic factor of NSCLC. Our experimental results are consistent with the above clinical correlation analysis results. Overexpression of BTK can significantly inhibit the proliferation, migration, and invasion of NSCLC cells and can block the G0/G1 tumor cell cycle, indicating that overexpression of BTK can inhibit the growth, migration, and invasion of NSCLC cells.

Preoperative computed tomography-based tumoral radiomic features prediction for overall survival in resectable non-small cell lung cancer.

The purpose of this study was to evaluate whether preoperative radiomics features could meliorate risk stratification for the overall survival (OS) of non-small cell lung cancer (NSCLC) patients. After rigorous screening, the 208 NSCLC patients without any pre-operative adjuvant therapy were eventually enrolled. We segmented the 3D volume of interest (VOI) based on malignant lesion of computed tomography (CT) imaging and extracted 1542 radiomics features. Interclass correlation coefficients (ICC) and LASSO Cox regression analysis were utilized to perform feature selection and radiomics model building. In the model evaluation phase, we carried out stratified analysis, receiver operating characteristic (ROC) curve, concordance index (C-index), and decision curve analysis (DCA). In addition, integrating the clinicopathological trait and radiomics score, we developed a nomogram to predict the OS at 1 year, 2 years, and 3 years, respectively. Six radiomics features, including gradient_glcm_InverseVariance, logarithm_firstorder_Median, logarithm_firstorder_RobustMeanAbsoluteDeviation, square_gldm_LargeDependenceEmphasis, wavelet_HLL_firstorder_Kurtosis, and wavelet_LLL_firstorder_Maximum, were selected to construct the radiomics signature, whose areas under the curve (AUCs) for 3-year prediction reached 0.857 in the training set (n=146) and 0.871 in the testing set (n=62). The results of multivariate analysis revealed that the radiomics score, radiological sign, and N stage were independent prognostic factors in NSCLC. Moreover, compared with clinical factors and the separate radiomics model, the established nomogram exhibited a better performance in predicting 3-year OS. Our radiomics model may provide a promising non-invasive approach for preoperative risk stratification and personalized postoperative surveillance for resectable NSCLC patients.

Prognostic value of pretherapeutic FDG PET/CT in non-small cell lung cancer with pulmonary lymphangitic carcinomatosis

Pulmonary lymphangitic carcinomatosis (PLC) is associated with a poor prognosis in patients with non-small cell lung cancer (NSCLC). We sought to determine prognostic value of pretherapeutic fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) in NSCLC with radiologically diagnosed PLC. We retrospectively reviewed 50 NSCLC patients with radiologically diagnosed PLC. Among eight clinical variables and five imaging parameters, metabolic PLC burden, which represents the overall tumor burden of PLC, and cPLC, which represents the location and extent of PLC in a three-grade system, were used. In multivariate analyses for progression-free survival, metabolic PLC burden (P = 0.0181), cPLC (P = 0.0401), and clinical stage (P = 0.0284) were identified as independent prognostic factors. High metabolic PLC burden had a worse prognosis, and the prognosis of cPLC3 was significantly worse than that of cPLC1 or cPLC2. In univariate analyses for overall survival, only age (P = 0.0073) was identified a prognostic factor. In conclusion, FDG PET/CT parameters were identified as independent prognostic factors in NSCLC with radiologically diagnosed PLC. Furthermore, a combination of anatomical and metabolic information about PLC obtained using FDG PET/CT provides insight into the overall tumor burden of PLC and is useful in predicting prognosis.

Can serum progranulin level be used as a prognostic biomarker in non-small cell lung cancer?

Progranulin has been considered to be a poor prognostic biomarker for some types of malignancies. However, the clinical significance of serum progranulin level and the prognostic value are still not explored in advanced stages of lung cancer. The current study investigates the prognostic significance of progranulin serum levels in advanced-stage non-small cell lung cancer (NSCLC) patients. This study involved 94 subjects (70 advanced-stage NSCLC patients and 24 healthy controls). Serum progranulin level was measured by enzyme-linked immunosorbent assay (ELISA) and was correlated with patient outcome. The association between circulating progranulin level and clinicopathological parameters was detected. Serum progranulin cut-off level predicting six-month survival was determined. Serum progranulin level was found significantly elevated in NSCLC patients than in the control group (p<0.001). We did not determine a significant difference between stage IIIB and stage IV NSCLC patients for serum progranulin levels (p=0.166). When we evaluated the laboratory parameters, only serum LDH level was found significantly correlated with serum progranulin level (p=0.043), also bone and liver metastasis showed a significant correlation with progranulin level (p=0.008 and p = 0.024, respectively). The cut-off level of serum progranulin in predicting six months of survival was determined as 16.03 ng/ml (AUC = 0.973, 95%Cl: 0.903-0.997, p<0.001) with 97.06% sensitivity and 88.89% specificity. Overall survival was determined shorter in patients with progranulin level ≥16 ng/ml than those with <16 ng/ml (p<0.001). Also, in the multivariate analysis using the Cox regression model serum progranulin level was found as an independent prognostic factor for NSCLC (p=0.001). Serum progranulin level may be a useful biomarker for predicting poor survival in advanced-stage NSCLC patients.

Populations particulières : patients de Performance Status 2 ou plus

Performance status (PS) is a measure of the patient’s overall condition. Karnofsky and ECOG (Eastern Cooperative Oncology Group) are the most widely used scales. A three-point conversion scale allows a strong correlation between both scores: ECOG 0-1 = Karnofsky 100-80%, ECOG 2 = Karnofsky 60-70%, ECOG 3-4 = Karnofsky 50-10%. Numerous factors, whether linked to cancer or to comorbidities, can affect PS. PS remains a major independent prognostic factor in NSCLC (non small cell lung cancer) and SCLC (small cell lung cancer), despite its flawed reproducibility and the heterogeneity of cancer patients with poor PS. As a matter of fact, PS should be regarded as a stratification factor in research. All guidelines take PS into account as a therapeutic decision making tool, especially in the case of chemotherapy for metastatic NSCLC. Targeted therapy should be considered in case of metastatic disease with molecular targets regardless of PS, for its high effectiveness and good safety profile. Data regarding immunotherapy are rather sketchy. Tolerance seems to be fine. Findings regarding efficacy warrant careful selection of patients who might benefit from this therapy. In light of the European Medicines Agency call, let us build studies dedicated to patients as frail as they come and enroll them in clinical trials in such a way that they benefit, among others, from therapeutic advances. In order to apply clinical research findings to the general population, specific groups of patients should be more involved.1877-1203/© 2022 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Signature based on RNA-binding protein-related genes for predicting prognosis and guiding therapy in non-small cell lung cancer.

Background: Studies have reported that RNA-binding proteins (RBPs) are dysregulated in multiple cancers and are correlated with the progression and prognosis of disease. However, the functions of RBPs in non-small cell lung cancer (NSCLC) remain unclear. The present study aimed to explore the function of RBPs in NSCLC and their prognostic and therapeutic value. Methods: The mRNA expression profiles, DNA methylation data, gene mutation data, copy number variation data, and corresponding clinical information on NSCLC were downloaded from The Cancer Genome Atlas, Gene Expression Omnibus, and the University of California Santa Cruz Xena databases. The differentially expressed RBPs were identified between tumor and control tissues, and the expression and prognostic value of these RBPs were systemically investigated by bioinformatics analysis. A quantitative polymerase chain reaction (qPCR) was performed to validate the dysregulated genes in the prognostic signature. Results: A prognostic RBP-related signature was successfully constructed based on eight RBPs represented as a risk score using least absolute shrinkage and selection operator (LASSO) regression analysis. The high-risk group had a worse overall survival (OS) probability than the low-risk group (p < 0.001) with 1-, 3-, and 5-year area under the receiver operator characteristic curve values of 0.671, 0.638, and 0.637, respectively. The risk score was associated with the stage of disease (p < 0.05) and was an independent prognostic factor for NSCLC when adjusted for age and UICC stage (p < 0.001, hazard ratio (HR): 1.888). The constructed nomogram showed a good predictive value. The P53, focal adhesion, and NOD-like receptor signaling pathways were the primary pathways in the high-risk group (adjusted p value <0.05). The high-risk group was correlated with increased immune infiltration (p < 0.05), upregulated relative expression levels of programmed cell death 1 (PD1) (p = 0.015), cytotoxic T-lymphocyte-associated protein 4 (CTLA4) (p = 0.042), higher gene mutation frequency, higher tumor mutational burden (p = 0.034), and better chemotherapy response (p < 0.001). The signature was successfully validated using the GSE26939, GSE31210, GSE30219, and GSE157009 datasets. Dysregulation of these genes in patients with NSCLC was confirmed using the qPCR in an independent cohort (p < 0.05). Conclusion: An RBP-related signature was successfully constructed to predict prognosis in NSCLC, functioning as a reference for individualized therapy, including immunotherapy and chemotherapy.

Construction of a redox-related gene signature for overall survival prediction and immune infiltration in non-small-cell lung cancer.

Background: An imbalance in the redox homeostasis has been reported in multiple cancers and is associated with a poor prognosis of disease. However, the prognostic value of redox-related genes in non-small-cell lung cancer (NSCLC) remains unclear. Methods: RNA sequencing data, DNA methylation data, mutation, and clinical data of NSCLC patients were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. Redox-related differentially expressed genes (DEGs) were used to construct the prognostic signature using least absolute shrinkage and selection operator (LASSO) regression analysis. Kaplan–Meier survival curve and receiver operator characteristic (ROC) curve analyses were applied to validate the accuracy of the gene signature. Nomogram and calibration plots of the nomogram were constructed to predict prognosis. Pathway analysis was performed using gene set enrichment analysis. The correlations of risk score with tumor stage, immune infiltration, DNA methylation, tumor mutation burden (TMB), and chemotherapy sensitivity were evaluated. The prognostic signature was validated using GSE31210, GSE26939, and GSE68465 datasets. Real-time polymerase chain reaction (PCR) was used to validate dysregulated genes in NSCLC. Results: A prognostic signature was constructed using the LASSO regression analysis and was represented as a risk score. The high-risk group was significantly correlated with worse overall survival (OS) (p < 0.001). The area under the ROC curve (AUC) at the 5-year stage was 0.657. The risk score was precisely correlated with the tumor stage and was an independent prognostic factor for NSCLC. The constructed nomogram accurately predicted the OS of patients after 1-, 3-, and 5-year periods. DNA replication, cell cycle, and ECM receptor interaction were the main pathways enriched in the high-risk group. In addition, the high-risk score was correlated with higher TMB, lower methylation levels, increased infiltrating macrophages, activated memory CD4+ T cells, and a higher sensitivity to chemotherapy. The signature was validated in GSE31210, GSE26939, and GSE68465 datasets. Real-time PCR validated dysregulated mRNA expression levels in NSCLC. Conclusions: A prognostic redox-related gene signature was successfully established in NSCLC, with potential applications in the clinical setting.

Pretreatment Albumin-to-Alkaline Phosphatase Ratio Is a Prognostic Marker in Lung Cancer Patients: A Registry-Based Study of 7077 Lung Cancer Patients.

Simple SummarySince the albumin-to-alkaline phosphatase ratio (AAPR) has shown promising prognostic prediction in cancer patients, the prognostic value of the AAPR was evaluated in a large cohort of 7077 lung cancer patients. We combined patient data from the Danish Lung Cancer Registry and the clinical laboratory information system (LABKA) and showed that a low AAPR was independently associated with an inferior median overall survival in non-small cell lung cancer patients and small cell lung cancer patients. Furthermore, data indicated a level-dependent correlation between the AAPR and survival and that the AAPR added additional prognostic value to the already well-established prognostic markers in lung cancer. Therefore, if our findings are validated in the future, the AAPR should be incorporated as a factor in the general prognostication of lung cancer patients.The albumin-to-alkaline phosphatase ratio (AAPR) is a novel promising prognostic marker in cancer patients. However, the evidence for its significance in lung cancer is scarce. Therefore, we assessed the prognostic value of the AAPR in a large cohort of lung cancer patients. Data on lung cancer patients diagnosed from January 2009 to June 2018 were extracted from the Danish Lung Cancer Registry and combined with data on the pretreatment serum AAPR level extracted from the clinical laboratory information system (LABKA). AAPR tertiles were applied as cutoffs. Cox proportional hazard models assessed the prognostic value of the AAPR. In total, 5978 non-small cell lung cancer (NSCLC) patients and 1099 small cell lung cancer (SCLC) patients were included. Decreasing AAPR level was significantly associated with declining median overall survival (OS) in NSCLC patients (medium vs. low AAPR, adjusted HR = 0.73 (95% confidence interval (CI) 0.68–0.79); high vs. low AAPR, adjusted HR = 0.68 (95% CI 0.62–0.73)) and in SCLC patients (medium vs. low AAPR, adjusted HR = 0.62 (95% CI 0.52–0.74); high vs. low, adjusted HR = 0.59 (95% CI 0.50–0.70)). In conclusion, the AAPR was an independent prognostic factor in NSCLC and SCLC patients. The correlation seems to be level dependent, with reducing survival found to be associated with decreasing AAPR level.

POM121 promotes proliferation and metastasis in non-small-cell lung cancer through TGF-β/SMAD and PI3K/AKT pathways.

Nuclear pore membrane protein 121 (POM121) is a novel biomarker involved in tumorigenesis and metastasis. However, little is known about the role of POM121 in non-small-cell lung cancer (NSCLC). The aim of this study was to detect the expression of POM121 in NSCLC and its relationship with clinicopathologic feature and cell biological behavior, and explore the underlying mechanisms. The expression of POM121 in NSCLC tissues and para-carcinoma tissues was compared by quantitative real-time PCR and immunohistochemistry analysis. The relationship between POM121 protein and clinicopathological characteristics in NSCLC was investigated. Roles of POM121 in NSCLC cells were investigated by CCK-8 assay, clone formation assay, transwell migration and invasion assay, and in vivo experiments. Variations of signaling pathways were determined by qRT-PCR and Western blot. The POM121 expression in NSCLC tissues was significantly higher than that in para-carcinoma tissues, both at the mRNA and protein level. The POM121 expression was related to sex, advanced differentiation, tumor diameter, lymph node metastases, distant metastases, American Joint Committee on Cancer (AJCC) stage, venous invasion, and perineural invasion in NSCLC. Kaplan-Meier analysis indicated that NSCLC patients with high POM121 expression had poor overall survival. Downregulation of POM121 inhibited cell proliferation, clone formation, migration and invasion. TGF-β/SMAD and PI3K/AKT pathways were involved in POM121-induced functional changes in NSCLC cells. POM121 plays an oncogenic role in NSCLC through TGF-β/SMAD and PI3K/AKT pathways. POM121 expression is a potential independent prognostic factor for NSCLC.

FP02.02 The Impact of Sex on Non-Small Cell Lung Cancer Survival in Canada

Lung cancer is the leading cause of cancer-related death in Canada. Non-small cell lung cancer (NSCLC) accounts for the majority of lung cancer cases, and while new treatments have been developed, survival outcomes remain poor. Literature from outside Canada indicates differences in NSCLC survival by sex. These differences cannot be explained by differences in stage, NSCLC subtype, age, or smoking history, indicating that sex may be an independent prognostic factor. The impact of sex on NSCLC survival has yet to be thoroughly examined in the Canadian context. Here we evaluate the impact of sex on survival outcomes among a population-based Canadian cohort of lung cancer patients. A retrospective cohort study was completed using real-world data from the Glans-Look Lung Cancer Database (GLD). The GLD contains demographic, clinical, pathological, treatment, and outcome data for all individuals diagnosed with NSCLC in Alberta, Canada, between 2010 and 2017. Descriptive statistics were used to characterize the cohort. To analyze the impact of sex on NSCLC survival, Kaplan-Meier estimators with log rank tests were used for comparisons between cohorts grouped by sex, stage, and subtype. Overall survival was defined as time from diagnosis to death from any cause. 8193 patients with complete data were included in analyses. Median age was 69.30 years (IQR 61.85-76.19), with 49.35% of the cohort being female. Median overall survival was 12.73 months (IQR 4.83–28.07), with 6277 (76.61%) patients deceased at end of follow-up. The highest proportion of cases (49.04%) were stage IV at diagnosis, and the most common histological subtypes were adenocarcinoma (55.35%), squamous cell carcinoma (SCC) (24.68%), and pathologically not otherwise specified (NOS) (9.79%). Survival analyses by stage indicated females had longer survival than males at every stage of diagnosis (p<0.01) (Figure). Analyses by subtype indicated that amongst those with adenocarcinoma, SCC, or pathological NOS, females had longer survival than males (p<0.01). Analyses by stage and subtype showed longer female survival for all stages of adenocarcinoma (p<0.01), and stage IV SCC (p<0.01) and pathological NOS (p=0.02) compared to males. These preliminary analyses suggest that females with NSCLC have longer survival than males with NSCLC at all stages of disease, and within the most common histological subtypes. These analyses suggest that survival trends among Canadian NSCLC patients are similar to those seen in other western countries, and that further research is needed to elucidate the consideration of sex as an independent prognostic factor for NSCLC.

Prognostic value of miR-1181 in non-small cell lung cancer and its regulatory effect on tumor progression.

Non-small cell lung cancer (NSCLC) is one of the most important causes of cancer-related death. miR-1181 has been reported to have roles in various cancer types and its function in the progression of NSCLC was investigated in the present study. A total of 118 patients with NSCLC were recruited and their tumor tissues were collected. The expression of miR-1181 in NSCLC tissues and cells was detected by reverse transcription-quantitative PCR. The prognostic value of miR-1181 was evaluated by Kaplan-Meier and Cox regression analysis and the roles of miR-1181 in cell proliferation, migration and invasion of NSCLC were analyzed by Cell Counting Kit-8 and Transwell assays. miR-1181 was indicated to be upregulated in NSCLC tissues and cell lines, and to be associated with lymph node metastasis and the TNM stage of patients. Patients with high miR-1181 expression had a poorer prognosis than those with low miR-1181 expression. miR-1181 levels and TNM stage were determined to be two independent prognostic factors for NSCLC. In addition, overexpression of miR-1181 exerted enhancing effects on cell proliferation, migration and invasion of NSCLC, while its knockdown inhibited these cellular processes. In conclusion, upregulation of miR-1181 in NSCLC was associated with lymph node metastasis and TNM stage of patients and was indicative of poor prognosis. miR-1181 was indicated to exert promoting effects on cell proliferation, migration and invasion of NSCLC cells and to be involved in tumor progression, providing novel insight for the development of biomarkers and therapies for NSCLC.

MiR-765 Acts as a Tumor Promoter and Indicates Poor Prognosis in Non-Small Cell Lung Cancer.

PurposeNon-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related death worldwide with poor prognosis. Accumulating evidence indicates that miR-765 is an important regulator in the progression and prognosis of various cancers. In this study, the function in the progression and prognosis of NSCLC was investigated.Patients and MethodsThe expression of miR-765 in NSCLC was analyzed by qRT-PCR. The effect of miR-765 on cell proliferation, migration, and invasion of NSCLC was evaluated by CCK8 and Transwell assay. Kaplan–Meier analysis and Cox regression analysis were employed to assess the prognostic value of miR-765.ResultsThe results demonstrated the significant upregulation of miR-765 in NSCLC tissues and cell lines relative to normal tissues and cells. High miR-765 expression was significantly correlated with the TNM stage of patients. Patients with high miR-765 expression showed a poorer prognosis than that of patients with low miR-765 expression. Cox analysis indicated that miR-765 could be considered as an independent prognostic factor for NSCLC. Additionally, the upregulation of miR-765 was revealed to promote NSCLC cell proliferation, migration, and invasion by targeting BMP6.ConclusionThe overexpression of miR-765 in NSCLC was associated with TNM stage and poor prognosis of patients. miR-765 served as a tumor promoter of NSCLC by regulating BMP6. These findings provide a potential biomarker and therapeutic target for the prognosis and treatment of NSCLC.

LncRNA CCDC144NL-AS1 Serves as a Prognosis Biomarker for Non-small Cell Lung Cancer and Promotes Cellular Function by Targeting miR-490-3p.

This study revealed the prognostic significance of long non-coding RNA (lncRNA) CCDC144NL-AS1 in NSCLC patients and discussed the effect and mechanism of proliferation, migration, and invasion of non-small cell lung cancer (NSCLC) cells. 128 pairs of NSCLC tissues and paracancerous tissues were collected, and qRT-PCR was used to detect the differential expression of lncRNA CCDC144NL-AS1 in all tissues and cells lines. Kaplan-Meier analysis and Cox proportional hazards model analysis were used to estimate the prognostic value of lncRNA CCDC144NL-AS1. CCK-8 and Transwell assays confirmed the effect of lncRNA CCDC144NL-AS1 on the proliferation, migration, and invasion of NSCLC. Bioinformatics was used to predict the microRNAs that lncRNA CCDC144NL-AS1 might bind to miR-490-3p. The regulation of lncRNA CCDC144NL-AS1 on miR-490-3p was verified by luciferase activity assay with wide type or mutation. The expression of lncRNA CCDC144NL-AS1 was enhanced in both NSCLC tissues and cell lines. Patients with overexpression of lncRNA CCDC144NL-AS1 have a poor prognosis, and lncRNA CCDC144NL-AS1 is an independent prognostic factor for NSCLC. Increased the relative expression level of lncRNA CCDC144NL-AS1 can promote the proliferation, migration, and invasion of NSCLC cells. LncRNA CCDC144NL-AS1 might target miR-490-3p. LncRNA CCDC144NL-AS1 can be used as an oncogene of NSCLC to predict patient prognosis and promote tumor proliferation, migration, and invasion by targeting miR-490-3p.