Serum miR-1228-3p and miR-181a-5p as Noninvasive Biomarkers for Non-Small Cell Lung Cancer Diagnosis and Prognosis

Background. Lung cancer is the leading cause of cancer-related mortality worldwide, and non-small cell lung cancer (NSCLC) accounts for over 80% of all lung cancers. Serum microRNAs (miRNAs), due to their high stability, have the potential to become valuable noninvasive biomarkers. This present study was aimed to identify the serum miRNAs expression signatures for the diagnosis and prognosis of NSCLC using bioinformatics analysis. Methods. A total of 12 miRNAs profiling studies have been identified in Pubmed, Gene Expression Omnibus (GEO), and ArreyExpress databases. Differentially expressed miRNAs (DEmiRNAs) were analyzed according to GEO2R online tool and RRA method from R. Then, prediction of DEmiRNAs’ target genes from TargetScan, PicTar, miRDB, Tarbase, and miRanda database. Furthermore, we using reverse transcription– quantitative polymerase chain reaction (RT-qPCR) to evaluate the expression levels of DEmiRNAs in serum samples obtained from NSCLC patients and healthy controls. Subsequently, the clinical significance of the tested miRNAs was determined using receiver operating characteristic (ROC) analysis and Cox regression analysis. Results. A total of 27 DEmiRNAs were identified and 5 of them (miR-1228-3p, miR-1228-5p, miR-133a-3p, miR-1273f, miR-545-3p) were significantly up-regulated and 4 of them (miR-181a-5p, miR-266-5p, miR-361-5p, miR-130a-3p) were significantly down-regulated in NSCLC patients compared with healthy controls. RT-qPCR validated that miR-1228-3p (P =0.006) and miR-181a-5p (P =0.030) were significantly differentially expressed in the serum of NSCLC patients and healthy controls. ROC analysis on miR-1228-3p and miR-181a-5p revealed the area under the curve (AUC) of 0.685 (95% confidence interval [CI], 0.563–0.806; P =0.006) and 0.647 (95% CI, 0.506–0.758; P =0.049). ROC analysis on miR-1228-3p combined miR-181a-5p revealed the AUC of 0.711 (95% CI, 0.593–0.828; P =0.002). Multivariate Cox regression analysis demonstrated that the high serum miR-1228-3p level was an independent factor for the poor prognosis of NSCLC patients. Conclusions. Serum miR-1228-3p and miR-181a-5p are potential noninvasive biomarkers for the diagnosis and prognosis of NSCLC patients.

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Prediction of Overall Survival for Early-stage Non-small Cell Lung Cancer via a Novel 7-gene Prognostic Signature and Allele Frequency Deviation (AFD)

10.21203/rs.3.rs-68377/v1 ◽

2020 ◽

Author(s):

Aisha AL-Dherasi ◽

Yuwei Liao ◽

Qi-Tian Huang ◽

Yichen Wang ◽

Rulin Hua ◽

...

Keyword(s):

Lung Cancer ◽

Allele Frequency ◽

Prognostic Model ◽

Cox Regression ◽

Gene Signature ◽

Small Cell ◽

Prognostic Signature ◽

Small Cell Lung ◽

Cox Regression Analysis ◽

Nsclc Patients

Abstract Background Due to the late and poor prognosis of non-small lung cancer(NSCLC), the mortality of patients is high, underlines the need to identify a credible prognostic marker for NSCLC patients. The aim of our study is to examine the association of allele frequency deviation (AFD) with the patient's survival, as well as identification and validation of a new prognostic signature to predict NSCLC overall survival(OS).Methods First, we developed a new algorithm to calculate AFD from whole-exome sequencing(WES) data, then we compared the predictability of the patient's survival between AFD, tumor mutation burden (TMB) and change of variants allele frequency (dVAF). Second, we overlapped the differentially expressed genes (DEGs) from our data with the genes associated with the survival of The Cancer Genome Atlas (TCGA) database to confirm all genes significantly related to the survival of lung cancer. We identified 149 genes, 31 of which are new genes and have not been reported for lung cancer, that was used to develop a new prognostic model. Lung cancer adenocarcinoma (LUAD) data from the TCGA database was used to validate the gene-signature model. The prognostic model relating to the genes was established and validated in training and LUAD validation groups.Results There was a significant association found between the high AFD value and poor survival among non-small cell lung cancer (NSCLC) patients. A novel seven genes (UCN2, RIMS2, CAVIN2, GRIA1, PKHD1L1, PGM5, CLIC6) were obtained through multivariate Cox regression analysis and significantly associated with NSCLC patients survival. Cox regression analysis confirmed that AFD and 7-gene signature are an independent prognostic marker in NSCLC patients. The AUC for 5-year survival in AFD and the AUC for 3-year survival in both training and validation groups were greater than 0.7.Conclusion As a result, AFD and 7-gene signatures were identified as new independent predictive factors used for predicting the survival among NSCLC patients.

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Identification and Prognostic Value Exploration of Radiotherapy Sensitivity-Associated Genes in Non-Small-Cell Lung Cancer

BioMed Research International ◽

10.1155/2021/5963868 ◽

2021 ◽

Vol 2021 ◽

pp. 1-14

Author(s):

Qing Ma ◽

Kai Geng ◽

Ping Xiao ◽

Lili Zeng

Keyword(s):

Lung Cancer ◽

Regression Analysis ◽

Risk Score ◽

Cox Regression ◽

Risk Group ◽

High Risk Group ◽

Small Cell ◽

Small Cell Lung ◽

Cox Regression Analysis ◽

Nsclc Patients

Background. Non-small-cell lung cancer (NSCLC) is a prevalent malignancy with high mortality and poor prognosis. The radiotherapy is one of the most common treatments of NSCLC, and the radiotherapy sensitivity of patients could affect the individual prognosis of NSCLC. However, the prognostic signatures related to radiotherapy response still remain limited. Here, we explored the radiosensitivity-associated genes and constructed the prognostically predictive model of NSCLC cases. Methods. The NSCLC samples with radiotherapy records were obtained from The Cancer Genome Atlas database, and the mRNA expression profiles of NSCLC patients from the GSE30219 and GSE31210 datasets were obtained from the Gene Expression Omnibus database. The Weighted Gene Coexpression Network Analysis (WGCNA), univariate, least absolute shrinkage and selection operator (LASSO), multivariate Cox regression analysis, and nomogram were conducted to identify and validate the radiotherapy sensitivity-related signature. Results. WGCNA revealed that 365 genes were significantly correlated with radiotherapy response. LASSO Cox regression analysis identified 8 genes, including FOLR3, SLC6A11, ALPP, IGFN1, KCNJ12, RPS4XP22, HIST1H2BH, and BLACAT1. The overall survival (OS) of the low-risk group was better than that of the high-risk group separated by the Risk Score based on these 8 genes for the NSCLC patients. Furthermore, the immune infiltration analysis showed that monocytes and activated memory CD4 T cells had different relative proportions in the low-risk group compared with the high-risk group. The Risk Score was correlated with immune checkpoints, including CTLA4, PDL1, LAG3, and TIGIT. Conclusion. We identified 365 genes potentially correlated with the radiotherapy response of NSCLC patients. The Risk Score model based on the identified 8 genes can predict the prognosis of NSCLC patients.

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Clinical Significance of Serum-Derived Exosomal LINC00917 in Patients With Non-Small Cell Lung Cancer

Frontiers in Genetics ◽

10.3389/fgene.2021.728763 ◽

2021 ◽

Vol 12 ◽

Author(s):

Dani Xiong ◽

Chuanlin Wang ◽

Zhaohui Yang ◽

Fusen Han ◽

Huaibing Zhan

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cancer Patients ◽

Cell Lung Cancer ◽

Cox Regression ◽

Small Cell ◽

Small Cell Lung ◽

Cox Regression Analysis ◽

Diagnostic Potential ◽

Nsclc Patients

Background: In this study, we aimed to explore the diagnostic potential of serum-based exosomal long intergenic noncoding RNA 917 (LINC00917) in non-small cell lung cancer (NSCLC).Methods: Exosomes were extracted from NSCLC patients’ serum samples. Exosomal LINC00917 expression levels were compared, by qRT-PCR, between cancer patients and healthy controls, as well as sub-populations of cancer patients. The association between exosomal LINC00917 expression and NSCLC patients’ clinicopathologic factors were investigated, and receiver operating characteristic (ROC) curves were drawn. In addition, NSCLC patients’ overall survivals (OSs) was examined based on exosomal LINC00917 expression and further evaluated by the cox regression analysis.Results: Serum-derived exosomal LINC00917 was highly expressed in NSCLC patients, and further upregulated in stage III/IV cancer patients. Exosomal LINC00917 yielded modestly good under the curve (AUC) values. Upregulated exosomal LINC00917 expression was closely associated with cancer patients’ advanced stages and shorter OSs.Conclusion: Serum-derived exosomal LINC00917 may hold diagnostic potential for patients with non-small cell lung cancer.

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Serum miR-185 Is a Diagnostic and Prognostic Biomarker for Non-Small Cell Lung Cancer

Technology in Cancer Research & Treatment ◽

10.1177/1533033820973276 ◽

2020 ◽

Vol 19 ◽

pp. 153303382097327

Author(s):

Jinghao Liu ◽

Yueting Han ◽

Xingyu Liu ◽

Sen Wei

Keyword(s):

Carcinoma In Situ ◽

Cox Regression ◽

Small Cell ◽

Clinicopathological Parameters ◽

Healthy Controls ◽

Small Cell Lung ◽

Cell Lung Carcinoma ◽

Cox Regression Analysis ◽

Nsclc Patients

Objective: MicroRNAs (miRNAs) have been found to play important roles in the development of non-small cell lung carcinoma (NSCLC). The aim of this study was to analyze the expression and clinical value of serum miR-185 in NSCLC. Methods: Serum miR-185 levels were detected in 146 NSCLC patients, 50 patients with carcinoma in situ, 25 patients with non-malignant lung diseases (NMLD), and 80 healthy controls using quantitative reverse transcription PCR. The correlation between serum miR-185 level and clinical status of NSCLC was explored. Results: The results revealed that serum miR-185 expression was progressively decreased in healthy controls, patients with NMLD, patients with carcinoma in situ and NSCLC patients. In addition, compared to carcinoembryonic antigen (CEA), serum miR-185 demonstrated better diagnostic accuracy for discriminating patients with carcinoma from healthy controls, NSCLC patients from healthy controls and NSCLC patients from patients with carcinoma in situ. In addition, serum miR-185 levels were significantly elevated in post-treated samples compared to the pre-treated samples. Moreover, reduced serum miR-185 was closely associated with unfavorable clinicopathological parameters and worse survival. Univariate and multivariate cox regression analysis confirmed that serum miR-185 was an independent prognostic indicator for NSCLC. Conclusions: Collectively, our findings have demonstrated that serum miR-185 might serve as a promising and robust biomarker for the early detection and prognosis prediction of NSCLC.

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MicroRNA-1298 is downregulated in non-small cell lung cancer and suppresses tumor progression in tumor cells

Diagnostic Pathology ◽

10.1186/s13000-019-0911-4 ◽

2019 ◽

Vol 14 (1) ◽

Cited By ~ 4

Author(s):

Zhonghai Du ◽

Jun Wu ◽

Juan Wang ◽

Yan Liang ◽

Sensen Zhang ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Cox Regression ◽

Small Cell ◽

Migration And Invasion ◽

Small Cell Lung ◽

Poor Overall Survival ◽

Cox Regression Analysis ◽

Nsclc Patients

Abstract Background MicroRNAs (miRNAs) have been reported to serve pivotal roles in tumorigenesis. This study sough to assess the expression and clinical significance of microRNA-1298 (miR-1298) in patients with non-small cell lung cancer (NSCLC), and explore the functional role of miR-1298 in tumorigenesis. Methods One hundred and twenty-one NSCLC patients were recruited in this study. The expression of miR-1298 was estimated using quantitative real-time PCR. Kaplan-Meier survival curves and Cox regression analysis were used to evaluate the prognostic value of miR-1298. Gain- and loss-of-function experiments were preformed to explore the biological function of miR-1298 in NSCLC cells. Results Expression levels of miR-1298 were downregulated in NSCLC tissues and cells compared with the corresponding normal controls. The decreased expression of miR-1298 was associated with patients’ lymph node metastasis and TNM stage. The low expression of miR-1298 predicted poor overall survival and served as an independent prognostic indicator in NSCLC patients. According to the cell experiments, NSCLC cell proliferation, migration and invasion were inhibited by the overexpression of miR-1298. Conclusion All the data indicated that the downregulation of miR-1298 predicts poor prognosis of NSCLC, and the overexpression of miR-1298 in NSCLC cells leads to inhibited tumorigenesis. The aberrant miR-1298 may serve as a novel biomarker and therapeutic target in NSCLC.

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Prediction of Overall Survival for Early-stage Non-small Cell Lung Cancer via a Novel 7-gene Prognostic Signature and Allele Frequency Deviation (AFD)

10.21203/rs.3.rs-80073/v1 ◽

2020 ◽

Author(s):

Aisha AL-Dherasi ◽

Yuwei Liao ◽

Qi-Tian Huang ◽

Yichen Wang ◽

Rulin Hua ◽

...

Keyword(s):

Lung Cancer ◽

Allele Frequency ◽

Prognostic Model ◽

Cox Regression ◽

Gene Signature ◽

Small Cell ◽

Prognostic Signature ◽

Small Cell Lung ◽

Cox Regression Analysis ◽

Nsclc Patients

Abstract Background: Due to the late and poor prognosis of non-small lung cancer(NSCLC), the mortality of patients is high, underlines the need to identify a credible prognostic marker for NSCLC patients. The aim of our study is to examine the association of allele frequency deviation (AFD) with the patient's survival, as well as identification and validation of a new prognostic signature to predict NSCLC overall survival(OS).Methods: First, we developed a new algorithm to calculate AFD from whole-exome sequencing(WES) data, then we compared the predictability of the patient's survival between AFD, tumor mutation burden (TMB) and change of variants allele frequency (dVAF). Second, we overlapped the differentially expressed genes (DEGs) from our data with the genes associated with the survival of The Cancer Genome Atlas (TCGA) database to confirm all genes significantly related to the survival of lung cancer. We identified 149 genes, 31 of which are new genes and have not been reported for lung cancer, that was used to develop a new prognostic model. Lung cancer adenocarcinoma (LUAD) data from the TCGA database was used to validate the gene-signature model. The prognostic model relating to the genes was established and validated in training and LUAD validation groups. Results: There was a significant association found between the high AFD value and poor survival among non-small cell lung cancer (NSCLC) patients. A novel seven genes (UCN2, RIMS2, CAVIN2, GRIA1, PKHD1L1, PGM5, CLIC6) were obtained through multivariate Cox regression analysis and significantly associated with NSCLC patients survival. Cox regression analysis confirmed that AFD and 7-gene signature are an independent prognostic marker in NSCLC patients. The AUC for 5-year survival in AFD and the AUC for 3-year survival in both training and validation groups were greater than 0.7.Conclusion: As a result, AFD and 7-gene signatures were identified as new independent predictive factors used for predicting the survival among NSCLC patients.

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Prognostic characterization of immune molecular subtypes in non-small cell lung cancer to immunotherapy

BMC Pulmonary Medicine ◽

10.1186/s12890-021-01765-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Chenlu Li ◽

Jingjing Pan ◽

Jing Luo ◽

Xupeng Chen

Keyword(s):

Lung Cancer ◽

Regression Analysis ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Cox Regression ◽

Small Cell ◽

Risk Scores ◽

Small Cell Lung ◽

Cox Regression Analysis ◽

Nsclc Patients

Abstract Background Non-small cell lung cancer (NSCLC) was usually associated with poor prognosis and invalid therapeutical response to immunotherapy due to biological heterogeneity. It is urgent to screen reliable biomarkers, especially immunotherapy-associated biomarkers, that can predict outcomes of these patients. Methods Gene expression profiles of 1026 NSCLC patients were collected from The Cancer Genome Atlas (TCGA) datasets with their corresponding clinical and somatic mutation data. Based on immune infiltration scores, molecular clustering classification was performed to identify immune subtypes in NSCLC. After the functional enrichment analysis of subtypes, hub genes were further screened using univariate Cox, Lasso, and multivariate Cox regression analysis, and the risk score was defined to construct the prognostic model. Other microarray data and corresponding clinical information of 603 NSCLC patients from the GEO datasets were applied to conduct random forest models for the prognosis of NSCLC with 100 runs of cross-validation. Finally, external datasets with immunotherapy and chemotherapy were further applied to explore the significance of risk-scores in clinical immunotherapy response for NSCLC patients. Results Compared with Subtype-B, the Subtype-A, associated with better outcomes, was characterized by significantly higher stromal and immune scores, T lymphocytes infiltration scores and up-regulation of immunotherapy markers. In addition, we found and validated an eleven -gene signatures for better application of distinguishing high- and low-risk NSCLC patients and predict patients’ prognosis and therapeutical response to immunotherapy. Furthermore, combined with other clinical characteristics based on multivariate Cox regression analysis, we successfully constructed and validated a nomogram to effectively predict the survival rate of NSCLC patients. External immunotherapy and chemotherapy cohorts validated the patients with higher risk-scores exhibited significant therapeutic response and clinical benefits. Conclusion These results demonstrated the immunological and prognostic heterogeneity within NSCLC and provided a new clinical application in predicting the prognosis and benefits of immunotherapy for the disease.

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OMRT-15. Multidisciplinary management of non-small cell lung cancer patients with leptomeningeal metastasis in the TKI era

Neuro-Oncology Advances ◽

10.1093/noajnl/vdab070.039 ◽

2021 ◽

Vol 3 (Supplement_2) ◽

pp. ii10-ii10

Author(s):

Kuan-Yu Chen ◽

Abel Po-Hao Huang

Keyword(s):

Lung Cancer ◽

Overall Survival ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Cox Regression ◽

Leptomeningeal Metastasis ◽

Small Cell ◽

Small Cell Lung ◽

Cox Regression Analysis ◽

Nsclc Patients

Abstract Background leptomeningeal metastasis (LM) is a devastating scenario in patients with non-small cell lung cancer (NSCLC), with an estimated median overall survival (OS) of 4–6 months from diagnosis. Several studies have clarified the prognosis of treatment modalities after LM. However, just a few studies have clarified the prognosis of LM patterns. We evaluate the prognosis based on various patterns of LM under multidisciplinary treatment (MDT). Method This retrospective study evaluated NSCLC patients treated at National Taiwan University Hospital between 2007–2019 with brain metastases (BM) and LM. LM was classified into LM only, LM concurrent with BM, and LM after BM. Treatments including systemic therapy, whole-brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), and intrathecal chemotherapy with Methotrexate (IT MTX) were recorded. BM excision was done by a neurosurgeon using minimally invasive neurosurgery. The MDT was done according to patients’ clinical situations. Kaplan-Meier methodology was used to describe overall survival OS. Multivariate Cox regression model was used to access prognostic factors. Result One hunderd patients with NSCLC CNS metastasis was included in this study. Median OS in patients with single, oligo and multiple BM was 42.0 months (95% CI= 0.12–83.89), 58.1 months (95% CI= 13.00–103.26), and 21.3 months (95% CI= 16.93–25.73), respectively. The median OS of all LM patients was 9.8 months. The median OS of LM after BM, concurrent BMLM, and LM only was 8 months (95% CI= 2.58–13.56), 41.5 months (95% CI= 0.00–94.36), and 18.5 months (95% CI=3.68–33.32), respectively. Multivariate Cox regression analysis showed only IT MTX (p= 0.010, HR= 0.392, 95%CI= 0.19–0.80) was associated with survival. Conclusion MDT in the TKI era has led to a dramatic improvement of OS in patients with LM (4–6 months vs. 9.8 months). NSCLC patients with LM only and concurrent BM LM has a better prognosis and longer survival, and thus are worth receiving intensive MDT care.

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Comprehensive Analysis of Acetylation-Related lncRNAs and Identified AC099850.3 as Prognostic Biomarker in Non-Small Cell Lung Cancer

Journal of Oncology ◽

10.1155/2021/4405697 ◽

2021 ◽

Vol 2021 ◽

pp. 1-19

Author(s):

Junliang Zhou ◽

Mingyan Zhang ◽

Huanhuan Dong ◽

Meiqi Wang ◽

Yue Cheng ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Cox Regression ◽

Small Cell ◽

Small Cell Lung ◽

Clinical Prognosis ◽

Cox Regression Analysis ◽

Potential Biomarker ◽

Nsclc Patients

The present study aimed to analyze the effects of acetylation-related lncRNAs in non-small-cell lung cancer (NSCLC). A total of 399 differentially expressed lncRNAs (DElncRNAs) have been identified between 497 NSCLC tissues and 54 normal tissues in the TCGA database, and 105 of which were correlated with acetylation regulators. By using univariate cox regression analysis and combining it with clinical prognosis information, 12 prognostic-related lncRNAs were selected for the subsequent analysis. The NSCLC patients were divided into two subgroups (cluster 1 and cluster 2) by clustering software, and immunocyte infiltration analysis, microenvironmental analysis, and clinical relevance analysis were performed between the two subgroups. A risk model was also built to further assess the prognosis value of prognostic-related lncRNAs in NSCLC patients. We found that AC099850.3 was significantly higher in both cluster 1 and high-risk subgroups, which may serve as a potential biomarker for the prognosis of NSCLC patients. Then, based on ceRNA competition mechanisms, the pathway enrichment of 105 acetylation-related lncRNAs was conducted by GO and KEGG analyses. We found the acetylation-related lncRNAs were primarily enriched in MAPK and EGFR signaling pathways, which were closely associated with NSCLC development. Finally, we validated the expression levels of AC099850.3 in NSCLC tissues and adjacent non-cancerous tissues and confirmed that AC099850.3 was significantly highly expressed in NSCLC tissues and cells. These results may provide clues for our understanding of the role of acetylation-related lncRNAs and valuable information for future clinical diagnosis and prognosis in NSCLC patients.

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Efficacy and toxicity hypofractionated radiotherapy for centrally located non-small cell lung cancer

Journal of Radiotherapy in Practice ◽

10.1017/s1460396921000376 ◽

2021 ◽

pp. 1-4

Author(s):

Tanzeel Janjua ◽

Fei Sun ◽

Katy Clarke ◽

Pete Dickinson ◽

Kevin Franks ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Cox Regression ◽

Early Stage ◽

Performance Status ◽

Small Cell ◽

Small Cell Lung ◽

Early Stage Lung Cancer ◽

Cox Regression Analysis

Abstract Aim: Centrally located early-stage non-small cell lung cancer in patients who are unfit for surgery are treated with fractionated radiotherapy. We present the outcomes of a moderately hypofractionated accelerated dose regimen of 50 Gy in 15 fractions from a single centre in the UK. Materials and methods: Electronic case notes and radiotherapy records of lung cancer patients treated between January 2014 and December 2016 were retrospectively reviewed. Adult Comorbidity Evaluation-27 score was used to evaluate comorbidities. Mean lung doses and percentage of lung receiving more than 20 Gy were calculated for all patients. Survival outcomes were estimated using Kaplan–Meier curves. Results: Fifty-three patients were included in the study; the median follow-up was 20.2 months. 87% of patients had stage I disease. There was no 30-day post-treatment mortality. Ninety-day mortality rate after radiotherapy was 3.8%. Grade 2 pneumonitis was seen in five patients while no grade 3 or 4 pneumonitis was observed. The median progression-free survival (PFS) and overall survival (OS) were 18.5 months and 28.2 months, respectively. The estimated 1 and 2 years PFS were 62.3% and 41.3%, respectively, and OS were 77.4% and 56.6%, respectively. Worsening performance status was associated with worse survival on cox regression analysis. Disease relapsed in 36% of patients. 7.5% of patients with relapsed disease had infield recurrence. Findings: 50 Gy in 15 fractions radiotherapy for central early-stage lung cancer is a feasible choice that requires further randomised trials.

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