Marker In Lung Cancer Patients Research Articles

Evaluating the predictive significance of systemic immune-inflammatory index and tumor markers in lung cancer patients with bone metastases.

This study aims to develop a predictive model for identifying lung cancer patients at elevated risk for bone metastases, utilizing the Unified Immunoinflammatory Index and various tumor markers. This model is expected to facilitate timely and effective therapeutic interventions, especially in the context of the growing significance of immunotherapy for lung cancer treatment. A retrospective analysis was conducted on 324 lung cancer patients treated between January 2019 and January 2021. After meeting the inclusion criteria, 241 patients were selected, with 56 exhibiting bone metastases. The cohort was divided into a training group (169 patients) and a validation group (72 patients) at a 7:3 ratio. Lasso regression was employed to identify critical variables, followed by logistic regression to construct a Nomogram model for predicting bone metastases. The model's validity was ascertained through internal and external evaluations using the Concordance Index (C-index) and Receiver Operating Characteristic (ROC) curve. The study identified several factors influencing bone metastasis in lung cancer, such as the Systemic Immune-Inflammatory Index (SII), Carcinoembryonic Antigen (CEA), Neuron Specific Enolase (NSE), Cyfra21-1, and Neutrophil-to-Lymphocyte Ratio (NLR). These factors were incorporated into the Nomogram model, demonstrating high validation accuracy with C-index scores of 0.936 for internal and 0.924 for external validation. The research successfully developed an intuitive and accurate Nomogram prediction model utilizing clinical indicators to predict the risk of bone metastases in lung cancer patients. This tool can be instrumental in aiding clinicians in developing personalized treatment plans, thereby optimizing patient outcomes in lung cancer care.

Clinical Value of Seven Autoantibodies Against Tumor-Associated Antigens and Tumor Markers in Lung Cancer Patients: A Retrospective Analysis from a Single Institution.

Background: Lung cancer screening is not limited to low dose computed tomography (LDCT). Recently, molecular biomarkers have been shown to have the potential to improve the current state of early lung cancer detection. The current study determined the efficiency of seven autoantibodies against tumor-associated antigens (7-AABs) and tumor markers in patients with lung cancer. Materials and Methods: An enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of 7-AABs and tumor markers in 354 patients with lung cancer and 108 patients with benign pulmonary disease under care at Ethics Committee of Tianjin Medical University General Hospital. Results: The sensitivity, specificity, positive predictive value (PPV), and area under the receiver operating characteristic (ROC) curve of 7-AABs were 30.0%, 84.3%, 86.3%, and 0.61, respectively. When combining the 7-AABs and tumor markers, the sensitivity was 68.6%, the specificity was 52.8%, and the area under the ROC curve was 0.72. The 7-AABs positive expression rate in lung cancer patients was significantly higher than patients with benign pulmonary diseases (30.1% vs 15.7%); however, the 7-AABs positive expression rate was affected by clinical features and pathologic stages. When combining 7-AABs and tumor markers, the combined 7-AABs and tumor marker positive expression rate increased to 68.6%. Conclusion: Based on this study and previous literature, the supplemental diagnostic value of 7-AABs has been confirmed; however, due to the low sensitivity, the value of 7-AABs alone in lung cancer screening is limited. The combination of 7-AABs and tumor markers has improved sensitivity and positivity, but decreased specificity, which makes their performance in cancer screening and early detection worthy of further research.

RAI3 expression is not associated with clinical outcomes of patients with non-small cell lung cancer

PurposeRetinoic acid inducible protein 3 (RAI3) has been suggested as prognostic biomarker in several cancer types. The present study aimed to examine the role of RAI3 expression in non-small cell lung cancers (NSCLCs).MethodsRAI3 protein expression was evaluated by immunohistochemistry in tissue microarray (TMA) sections from a retrospective cohort of more than 600 surgically resected NSCLCs and results were compared with clinicopathological features and follow-up data.ResultsWhile membranous RAI3 immunostaining was always strong in benign lung, strong RAI3 staining was only detectable in 14.7% of 530 interpretable NSCLCs. Within NSCLC subtypes, immunostaining intensity for RAI3 was significantly decreased in large cell lung cancers (LCLCs) and squamous cell carcinomas (SQCCs) relative to lung adenocarcinomas (LUACs) (P < 0.0001 each). However, RAI3 staining was neither associated with pathological features of NSCLCs nor with survival of patients (P = 0.6915).ConclusionOur study shows that RAI3 expression was not associated with clinical outcomes of NSCLC patients and cannot be considered as prognostic marker in lung cancer patients.

Bioinformatics analysis identifies key genes of prognostic value in lung cancer

Lung cancer is the most common human malignancy worldwide and can be divided into different types of carcinomas depending on their pathological features. Advances in medical science and technology have led to the identification of some lung cancer-related marker genes, including EGFR (epidermal growth factor receptor), BRAF (B-Raf proto-oncogene), RAS (RAS proto-oncogene, GTPase) and HER2 (human epidermal growth factor receptor 2). However, the underlying biomarker and key genes associated with different types of lung cancer are still poorly understood. In this study, we analyzed a GEO (Gene Expression Omnibus) dataset and identified 28 upregulated intersection DEGs (different expression genes) and 125 downregulated intersection DEGs among AC (adenocarcinoma), PTC (primary typical carcinoid), PLCC (primary large cell carcinoma), PLCNC (primary large cell lung carcinoma) and PSCLC (primary small cell lung carcinoma). Through PPI (protein-protein interaction) network analysis, we identified 14 genes among the DEGs, namely MFAP4 (microfibril-associated protein 4), PDZD2 (PDZ domain containing 2), FBLN1 (fibulin 1), FBLN5 (fibulin 5), EFEMP1 (EGF containing fibulin extracellular matrix protein 1), KDR (kinase insert domain receptor), S1PR1 (sphingosine-1-phosphate receptor 1), CAV1 (caveolin 1), GRK5 (G protein-coupled receptor kinase 5), EDNRA (endothelin receptor type A), EDNRB (endothelin receptor type B), CALCRL (calcitonin receptor-like receptor), PTGER4 (prostaglandin E receptor 4), and ADRB1 (adrenoceptor beta 1), which were found to be downregulated in different subtypes of lung cancer and associated with poor survival outcomes. In addition, most of the screened DEGs demonstrated good predictive ability in LUAD (lung adenocarcinoma) and LUSC (lung squamous cell carcinoma). Among them, MFAP4 was found to promote cell proliferation while also suppressing cell migration and angiogenesis. In summary, we propose MFAP4, PDZD2, FBLN1, FBLN5, EFEMP1, KDR, S1PR1, CAV1, GRK5, EDNRA, EDNRB, CALCRL, PTGER4 and ADRB1 as potential prognostic markers in lung cancer patients.

Nucleolin; A tumor associated antigen as a potential lung cancer biomarker

Lung cancer is a primary cause of mortality in many communities. The poor prognosis and clinical outcome of this cancer are mostly attributable to its advanced stage upon diagnosis, and as a result, it places a significant cost on public health across the globe. The majority of patients experience severe adverse effects from conventional therapies that involve nonspecific invasion of both healthy and malignant cells. Furthermore, no particular tumor marker has been developed to evaluate the patients' status and prognosis. NCL as one of the vital nuclear proteins is involved in various cellular activities, including ribosome assembly and rRNA processing. Research have shown that following malignant transformation in lung cancer cells, both the cytosolic and plasma membrane levels of this protein rise dramatically. Furthermore, signaling generated by the surface nucleolin significantly enhances tumor proliferation, differentiation, and angiogenesis. On the other hand, findings showed that altering the size and other properties of tumor cells may influence the expression pattern of nucleolin. Therefore, in the current study, we intend to review the role of nucleolin in the development and progression of lung cancer cells and also evaluate its potential as a prognostic, therapeutic as well as diagnostic marker in lung cancer patients.

The Roles of EXO1 and RPA1 Polymorphisms in Prognosis of Lung Cancer Patients Treated with Platinum-Based Chemotherapy.

Background Lung cancer is one of the major causes of cancer-related mortality worldwide. DNA repair and damage response contribute to genomic instability that accompanies tumor progression. In this study, we focus on evaluating association between DNA repair polymorphisms of EXO1, RPA1, and prognosis in lung cancer patients whom received platinum-based chemotherapy. Methods 593 lung cancer patients were recruited in this study. We performed genotyping of 19 single nucleotide polymorphisms (SNPs) by Sequenom MassARRAY. Cox regression analysis was used to assess overall survival (OS) and progression-free survival (PFS) among SNP genotypes. Results Significant differences in PFS and OS were observed in RPA1 rs5030740, EXO1 rs1776148, and rs1047840. Results showed that patients with CC genotype in rs5030740 (recessive model: P = 0.034) had a better PFS. Patients with AA or/and AG genotypes in rs1776148 (additive model: P = 0.004; dominant model: P = 0.048) and AA genotype in rs1047840 (recessive model: P = 0.023) had longer OS. We also demonstrated differences in subgroup analysis between rs5030740, rs1776148, rs1047840, and prognosis. Conclusions Our results indicated that EXO1 rs1776148, rs1047840, and RPA1 rs5030740 were significantly associated with prognosis of lung cancer. Rs1776148, rs1047840, and rs5030740 may act as prognosis markers in lung cancer patients with platinum-based chemotherapy.

Identification of necroptosis-related gene signature and characterization of tumour microenvironment infiltration in non-small-cell lung cancer.

Necroptosis is a programmed necrosis in a caspase‐independent fashion. The role of necroptosis‐related genes (NRGs) in lung cancer remains unknow. Herein, we classified TCGA‐LUAD cohort into two necroptosis‐related subtypes (C1 and C2) by consensus clustering analysis. The result showed that subtype C1 had a favourable prognosis and higher infiltration levels of immune cells. Moreover, subtype C1 was more activated in immune‐associated pathways. Then, we established an NRG prognosis model (NRG score) composed of six NRGs (RIPK3, MLKL, TLR2, TLR4, TNFRSF1A, NDRG2) and divided the cohort into low‐ and high‐risk group. We found that the NRG score was associated with prognosis, tumour immune microenvironment and tumour mutation burden. We also constructed an accurate nomogram model to improve the clinical applicability of NRG score. The result indicated that NRG score may be an independent prognostic marker for lung cancer patients. Taken together, we established a prognosis model that may deepen the understanding of NRGs in lung cancer and provide a basis for developing more effective immunotherapy strategies.

Polymorphism in Thymidylate Synthase Gene Predicts Survival and Toxicity in North Indian Lung Cancer Patients Undergoing Platinum-Based Doublet Chemotherapy.

With an estimated 1.8 million deaths, lung cancer is one of the widely reported malignancies, with substantial morbidity and mortality rates. Thymidylate synthase (TS) is an important drug target for platinum-based doublet chemotherapy as it is the only de novo source of thymidylate production in the cell. TS polymorphisms in the 5'UTR of Thymidylate synthase enhancer region (TSER) 2R/3R and 3'- UTR 1494del6 are investigated in this study. A total of 700 lung cancer patients with platinum-based doublet chemotherapy were recruited in this study. TSER (2R/3R) and TS 1494del6 polymorphisms in North Indian lung cancer patients were examined, and statistical analysis was performed. According to our findings, patients with the wild genotype (2R/2R) for the TSER polymorphism had a longer median survival time as compared to patients harboring the mutant type genotype (3R/3R) [MST=9.77 vs. 7.57 months; p=0.04]. On the contrary, patients with the mutant 14946del6 polymorphism (-6/-6) had a longer survival time than patients with the wild-type genotype (+6/+6) [MST=7.23 vs. 9 months]. Further, our findings elucidated that the patients with heterozygous genotype (2R3R) for TSER polymorphism had a 2.30-fold increased risk of developing leukopenia (AOR=2.30, 95% CI=0.96-5.52; p=0.05). A substantial risk of 5.14-fold constipation was found in heterozygous genotype (2R3R) when intermediate grade 2 toxicity was compared with low toxicity (grade 1) (p=0.007).An increased risk of nausea/vomiting was observed in patients with mutant genotype (-6/-6bp) for 1494 ins/del6 polymorphism compared to patients with wild-type genotype (+6/+6bp) (AOR= 2.77; 95%CI=1.10-6.96, p=0.03). According to our findings, TSER and the 1494del6 polymorphism may operate as a prognostic marker in lung cancer patients receiving platinum-based chemotherapy. Furthermore, TS polymorphisms may influence the onset of platinum-related toxicity, such as hematological and gastrointestinal toxicity. These findings might facilitate therapeutic decisions for individualized therapy in lung cancer patients.

Clinical application of serum tumor abnormal protein combined with tumor markers in lung cancer patients.

Aim: To explore the clinical application of tumor abnormal protein (TAP) combined with tumor markers in the diagnosis of lung cancer. Methods: Samples from 248 lung cancer patients and 59 patients with benign lung diseases were tested for TAP and tumor markers pro-gastrin-releasing peptide, carcinoembryonic antigen, NSE, CYFRA 21-1 and CA72-4. Results: The sensitivity of TAP and CYFRA 21-1 in the lung cancer group was significantly higher than that of the other indexes. TAP combined with NSE and CYFRA 21-1 or combined with NSE, CYFRA 21-1 and squamous cell carcinoma antigen detection could reduce detection indicators under the premise it does not reduce the sensitivity and accuracy of lung cancer diagnosis, and at the same time could improve the specificity, positive predictive value and positive likelihood ratio of detection. Conclusion: TAP detection represents a promising diagnostic tool. It is also suggested that combination with established tumor markers and comprehensive judgment could improve the accuracy of lung cancer auxiliary diagnosis.

Evaluation of hepatic CYP3A enzyme activity using endogenous markers in lung cancer patients treated with cisplatin, dexamethasone, and aprepitant.

Aprepitant is used with dexamethasone and 5-HT3 receptor antagonists as an antiemetic treatment for chemotherapy, including cisplatin. Aprepitant is a substrate of cytochrome P450 (CYP) 3A4 and is known to cause its inhibition and induction. In addition, dexamethasone is a CYP3A4 substrate that induces CYP3A4 and CYP3A5 expression. In this study, we aimed to quantitatively evaluate the profile of CYP3A activity using its endogenous markers in non-small cell lung cancer patients receiving a standard cisplatin regimen with antiemetics, including aprepitant. Urinary 11β-hydroxytestosterone (11β-OHT)/testosterone concentration ratio and plasma 4β-hydroxycholesterol (4β-OHC) concentrations were measured before and after cisplatin treatment (days 1, 4, and 8). CYP3A5 was genotyped, and plasma aprepitant concentrations were measured on day 4 to examine its influence on CYP3A endogenous markers. The urinary 11β-OHT/testosterone concentration ratio in the 35 patients included in this study increased by 2.65-fold and 1.21-fold on days 4 and 8 compared with day 1, respectively. Their plasma 4β-OHC concentration increased by 1.46-fold and 1.66-fold, respectively. The mean plasma aprepitant concentration on day 4 was 1,451ng/mL, which is far lower than its inhibitory constant. The allele frequencies of CYP3A5*1 and CYP3A5*3 were 0.229 and 0.771, respectively. In patients with the CYP3A5*1 allele, the plasma 4β-OHC concentration was significantly lower at baseline but more potently increased with chemotherapy. CYP3A activity was significantly induced from day 4 to day 8 in patients receiving cisplatin and three antiemetic drugs.

Histone Deacetylase as a Valuable Predictive Biomarker and Therapeutic Target in Immunotherapy for Non-Small Cell Lung Cancer.

PurposeHistone deacetylase inhibitors (HDACis) are epigenetic regulators and used clinically for hematopoietic malignancies. Recently, HDACis have received attention as a factor that modulates the immune system. In this study, the role of histone deacetylase (HDAC) expression as a predictive marker in lung cancer patients who were treated with immune checkpoint inhibitors (ICIs) and the role of HDACi and ICI combination treatment in the mouse tumor model were analyzed.Materials and MethodsThe overall response rate (ORR) and progression-free survival (PFS) were analyzed by the expression of HDAC. In vitro assay, the mRNA and protein expression levels of cytokines and programmed death-ligand 1 (PD-L1) were analyzed after HDACi treatment. In vivo assay, TC-1 tumor-bearing mice were treated with HDACi and mouse programmed cell death 1 (PD-1) inhibitor.ResultsThe HDAC6 low expression group showed high ORR and prolonged PFS. When the selective HDAC6 inhibitor was administered to the A549 cell line, the levels of interleukin-1β and interleukin-6 decreased and the expression of PD-L1 was reduced. Mice that received both the mouse PD-1 inhibitor and pan-HDACi had a smaller tumor size than that of the mice from the control group. Moreover, mice treated with the mouse PD-1 inhibitor and pan-HDACi generated greater numbers of E7-specific CD8+ T cells.ConclusionHDAC6 expression can predict the prognosis of non–small cell lung cancer patients who were treated with ICIs. Furthermore, co-treatment with HDACi and PD-1 inhibitor was shown to decrease the tumor growth rate and create a favorable tumor microenvironment for cytotoxic T lymphocytes in the TC-1 mouse model.

CD44 Promotes Lung Cancer Cell Metastasis through ERK-ZEB1 Signaling.

Simple SummaryLung cancer treatment has always been challenging as its metastasis rate is higher than other cancers. Cancer stemness promotes cancer metastasis, and it is important to understand the mechanism behind the cancer-stemness-mediated metastasis. CD44 is a well-known cancer stem cell marker and plays a role in tumor metastasis in different cancer types. In this study, we investigated the role of CD44 in lung cancer metastasis by using clinical studies as well as in vitro and in vivo studies. We found that CD44 promotes the migration and invasion abilities of lung cancer cells through ERK–ZEB1 signaling. This study provided evidence that CD44 may be a possible therapeutic target to decrease lung cancer metastasis.Lung cancer is a malignancy with high mortality worldwide, and metastasis occurs at a high frequency even when cancer spread is not detectable at primary operation. Cancer stemness plays an important role in malignant cancer behavior, treatment resistance, and cancer metastasis. Therefore, understanding the molecular pathogenesis behind cancer-stemness-mediated metastasis and developing effective approaches to prevent metastasis are key issues for improving cancer treatment. In this study, we investigated the role of CD44 stemness marker in lung cancer using in vitro and clinical studies. Immunohistochemical staining of lung cancer tissue specimens revealed that primary tumors with higher CD44 expression showed increased metastasis to regional lymph nodes. Flow cytometry analysis suggested that CD44 positive cells were enriched in the metastatic lymph nodes compared to the primary tumors. CD44 overexpression significantly increased migration and invasion abilities of lung cancer cells through CD44-induced ERK phosphorylation, ZEB1 upregulation, and Claudin-1 downregulation. Furthermore, ERK inhibition suppressed the migration and invasion abilities of CD44-overexpressing lung cancer cells. In summary, our in vitro and clinical results indicate that CD44 may be a potential prognostic and therapeutic marker for lung cancer patients.

Study of Programmed Death Ligand 1 and EGFR/HER2 Expression in Non-Small-Cell Lung Carcinoma With a Clinicopathological Spectrum.

Non-small-cell lung carcinoma (NSCLC) is a disease characterized by the upregulation of programmed death ligand 1 (PD-L1) along with alterations in epidermal growth factor receptor (EGFR) and HER2-neu (HER2) amplification in addition to EGFR mutation. In the present study, the expression of PD-L1 and EGFR and HER2-neu in NSCLC was studied and their expression in relation to various clinicopathological parameters was analysed. We studied 49 core biopsy specimens of NSCLC for PD-L1, EGFR and HER2-neu expressions using immunohistochemistry. Scoring was based on the intensity and percentage of tumour cells expressing the immunomarkers. PD-L1, EGFR and HER2-neu expression was seen in 20.4%, 32.7% and 14.2% of NSCLC, respectively. The analysis showed no significant difference in PD-L1 expression in relation to any clinicopathological parameters. Low or negative EGFR expression was significantly associated with positive lymph node status (P=0.04). HER2-neu expression showed a significant difference in relation to tumour histology (adenocarcinoma; P=0.01). Also, there was no difference noted with PD-L1 expression in relation to EGFR and HER2-neu expression. As our study has a small number of cases, the validation of the predictive and prognostic value of these markers in lung cancer patients requires further studies.

Circulating tumor DNA in advanced non-small-cell lung cancer patients with HIV is associated with shorter overall survival: Results from a Phase II trial (IFCT-1001 CHIVA)

IntroductionHIV is an exclusion criterion for most lung cancer (LC) trials, however LC is the most common non-AIDS-defined malignancy in people living with HIV (PLHIV), poorer prognosis than the general population. Circulating tumor DNA (ctDNA) was a prognostic marker in LC patients from the general population. This study assessed ctDNA’s prognostic value in PLHIV from a dedicated phase II trial. MethodsOverall, 61 PLHIV with advanced non-squamous non-small-cell lung cancer (NSCLC) participated in the IFCT Phase II trial evaluating first-line four-cycle carboplatin (Ca) AUC5 pemetrexed (P) 500 mg/m2 induction therapy every 3 weeks, followed by P maintenance therapy. Blood samples collected before treatment were analyzed to detect ctDNA using ultra-deep targeted next-generation-sequencing (NGS). ResultsAppropriate samples were available from 55 PLVIH and analyzed for ctDNA detection. Including 42 males (76.4 %), 52.9 years median age, 51 smokers (92.7 %), five with non-squamous NSCLC Stage III (9%), 50 Stage IV (91 %), and performance status (PS) 0−2. ctDNA was detected in 35 patients (64 %), 22 with high and 13 with low ctDNA levels. Overall, 77 % were positive for TP53, 29 % for KRAS, and 11 % for STK11 mutations, more than one alteration was detected in 43 % of samples. Multivariate analysis showed that positive ctDNA was significantly associated with shorter PFS (HR, 4.31, 95 %CI: 2.06−8.99, p < 0.0001), and shorter OS (HR, 3.52, 95 %CI: 1.72−7.19, p < 0.001). Moreover, OS was significantly longer for patients with low ctDNA levels at diagnosis as compared to high (p = 0.01). ConclusionWe show that ctDNA detection using ultra-deep NGS is an independent prognostic factor in PLHIV with advanced NSCLC.

Pulmonary Micro-Ecological Changes and Potential Microbial Markers in Lung Cancer Patients.

The relationship between the microbiome and disease has been investigated for many years. As a highly malignant tumor, biomarkers for lung cancer are diverse. However, precision of these biomarkers has not yet been achieved. It has been confirmed that lung microecology changes in lung cancer patients compared with healthy individuals. Furthermore, the abundance of some bacterial species shows obvious changes, suggesting their potential use as a microbial marker for the detection of lung cancer. In addition, recent studies have confirmed that inflammation, immune response, virulence factors, and metabolism may be potential mechanisms linking the microbiome with carcinogenesis. In this review, microbiome studies of lung cancer, potential mechanisms, potential microbial markers, and the influence of the microbiome on the diagnosis and treatment of lung cancer are summarized, providing theoretical strategies for the diagnosis and treatment of lung cancer.

JMJD8 Promotes Malignant Progression of Lung Cancer by Maintaining EGFR Stability and EGFR/PI3K/AKT Pathway Activation

JMJD8 is a JmjC domain-containing protein that has not been widely examined, despite its potential role in malignant tumor development. The underlying biological functions and molecular mechanisms of JMJD8 in non-small-cell lung cancer (NSCLC) remain unclear. Herein, we explored the relationship between JMJD8 and the activation of malignancy pathways in NSCLC. Immunohistochemical analyses revealed that high JMJD8 expression significantly correlated with cell differentiation and advanced TNM stages of NSCLC. The overexpression of JMJD8 promoted cell proliferation and invasion in vitro. Upon JMJD8 knockdown in lung cancer cell lines, cyclin B1, RhoA, RhoC, MMP9, and N-cadherin were down-regulated, and p21 and E-cadherin were conversely up-regulated. Key factors in the PI3K/AKT signaling pathway, such as p‑AKT, showed clear decreases in expression; additionally, the expression of epidermal growth factor receptor (EGFR), which functions upstream of PI3K, was altered. Co-immunoprecipitation experiments indicated that JMJD8 interacts with EGFR, and JMJD8 knockdown accelerated EGFR degradation. Our results suggested that JMJD8 functions as an oncogenic regulator in NSCLC. We found that JMJD8 promotes carcinogenic activity in NSCLC cells by facilitating EGFR stability, thereby activating the downstream PI3K/AKT signaling pathway. JMJD8 shows potential as a prognostic marker for lung cancer patients, providing a new target for therapeutic strategies.

Effect of phenotypic detection of circulating tumor cells marked by epithelial-mesenchymal transformation on the prognosis of lung cancer: A protocol for systematic review and meta-analysis.

Background:To explore the significance of phenotype detection of circulating tumor cells (CTCs) based on epithelial-mesenchymal transition (EMT) labeling to evaluate the prognosis of lung cancer.Methods:Database was retrieved from China National Knowledge Infrastructure (CNKI), Chinese Biomedical literature Database (CBM), Chinese Scientific and Journal Database (VIP), Wan Fang database, PubMed, and EMBASE. Based on EMT on overall survival (OS) and disease-free survival (DFS), hazard ratios (HRs) and its 95% of confidence intervals (CIs) were applied to assess the prognostic effect of CTCs. RevMan 5.3 and STATA 16.0 software were adopted to perform the meta-analysis.Results:Based on EMT in terms of the prognosis of patients suffering from lung cancer, this study comprehensively reviewed and evaluated the available evidence of phenotype detection of CTCs.Conclusion:Based on EMT in the prognosis of patients who developed with lung cancer, our findings proved the effect of phenotype detection of CTCs. Such studies may reveal a new prognostic marker for lung cancer patients and help clinicians and health professionals make clinical decisions.OSF Registration Number:DOI 10.17605/OSF.IO/E7KAZ.

The utilization pattern of serum tumor markers in lung cancer patients: A population‐based retrospective descriptive study

BackgroundThe trends in usage of tumor markers, including CEA, SCC, NSE, Cyfra21‐1, and ProGRP, in Chinese lung cancer patients in the real‐world setting are not fully investigated.MethodsA retrospective descriptive study was conducted using the database of Qilu Hospital of Shandong University, China between January 2013 and December 2017, involving patients primarily diagnosed with NSCLC or SCLC. Utilization trends by first discharge year, utilization rates within different durations before and after first discharge date, and combined utilization patterns of multiple tumor markers were analyzed.ResultsThe utilization of all these tumor markers showed increased from 2013 to 2017. CEA, Cyfra21‐1, and NSE were the most frequently detected, which increased slightly from around 50% in 2013 to around 78% in 2017 in NSCLC and from around 70% in 2013 to around 92% in 2017 in SCLC. CEA, Cyfra21‐1, and NSE were the most commonly measured within 3 months before first diagnosis with approximately 65% in NSCLC and 80% in SCLC, and ProGRP had the lowest utilization (around 30%). CEA, NSE, and Cyfra21‐1 had the highest utilization rates after first diagnosis with both around 80% in NSCLC or SCLC. Combined usage of five tumor markers was ranked the first pattern in combined utilization.ConclusionsThis study suggests CEA, Cyfra21‐1, and NSE are the most frequently detected before or after first diagnosis of NSCLC or SCLC. However, SCC and ProGRP tests appeared to have relatively low usages. The utilization pattern was consistent with recommendations of guideline, but underutilization still existed.

Association of variations in platinum resistance-related genes and prognosis in lung cancer patients.

Purpose: We aimed to investigate the association of single-nucleotide polymorphisms (SNPs) in HMGB1, REV3L, and NFE2L2 with prognosis in lung cancer patients with platinum-based chemotherapy.Methods: We have recruited 348 lung cancer patients treated with platinum. Log-rank test and Cox regression analysis were used to assess overall survival (OS) and progression-free survival (PFS) among SNP genotypes.Results: The results revealed that patients carrying TC or CC genotype in REV3L rs462779 (HR=0.67, 95% CI=0.51-0.90, P=0.007) and AG or GG genotype in HMGB1 rs1045411 (HR=0.61, 95% CI=0.38-0.99, P=0.046) had a better overall survival. Additionally, carrying TC or TT genotype in rs462779 had a lower risk (OR=0.38, 95% CI=0.17-0.89, P=0.025) of lymph node metastasis, carrying AG or AA genotype in rs1045411 was significantly related to early T stage (OR=0.47, 95% CI=0.29-0.76, P=0.002). In stratified analysis, patients with TC or CC genotype in rs462779 were significantly associated with overall survival in male patients, never-smokers, patients with younger age (≤56), no family history of cancer, adenocarcinoma, advanced stage (stage III or IV), or ECOG PS 0-1. While patients with AG or GG genotype in rs1045411 were significantly associated with overall survival in patients with advanced stage (stage III or IV) or ECOG PS 0-1.Conclusion: Our results indicate that the TC or CC genotype in rs462779 and AG or GG genotype in rs1045411 are contributed to better overall survival. The REV3L rs462779 and HMGB1 rs1045411 may serve as prognosis markers in lung cancer patients with platinum-based chemotherapy.

P2.01-43 Pre-Therapeutic Markers and Scores Predict Response and Survival in Stage IV Lung Cancer Patients Independent of Histology

Lung cancer is the leading cause of death among all cancer entities. Identification of reliable and validated predictive and prognostic markers is important to estimate patients’ prognosis. By doing this, planning of treatment and adequate patient guidance would improve. Many studies investigated several predictive and prognostic markers in lung cancer patients. Never the less, most of them describe very selective cohorts. This study aims at investigating histology independent predictive and prognostic markers in stage IV lung cancer patients. We retrospectively analyzed 129 stage IV lung cancer patients who had been diagnosed and treated at a German tertiary care lung cancer center between 2015 and 2016. Patients’ characteristics in terms of age, gender, performance status, histology, smoking status, treatment modalities and molecular pathological findings were collected from patients’ charts. We extracted data sets from electronic patient records and compared anthropometric data, pre-therapeutic blood values as well as clinical scores and performed tests for prediction analysis Eight markers and scores could be identified to significantly alter prognosis in univariate analysis. Over the normal cut off elevated values of CRP (p <0.001), LDH (p <0.001), Neutrophil to Lymphocyte ratio (NLR) (p = 0.018) and Systemic Inflammation Index (SII) (p = 0.036) as well as decreased levels of MCV (p = 0.025) and total protein (p = 0.049) were significantly associated with reduced overall survival (OS). Furthermore, the higher the Glasgow Prognostic Score (GPS) (p <0.001) or the Lung Prognostic Index (PI-lung) (p <0.001) were the worse was the OS. Failure of first line treatment was significantly predicted by low albumin (p=0.006), lymphocytes (p = 0.032) and PNI (p = 0.001) levels, whereas low values of CRP (p <0.001), LDH (p = 0.042) and Thrombocyte to Lymphocyte ration (TLR) (p = 0.017) predict response to first line therapy. Multivariate analysis revealed CRP, PI-lung and GPS as independent prognostic factors regardless histology. Simply to obtain blood values and clinical scores provide histology independent markers for response to fist line treatment and survival in stage IV lung cancer patients.