Molecular identification of an immunity- and Ferroptosis-related gene signature in non-small cell lung Cancer

Abstract Background Lung cancer is one of the dominant causes of cancer-related deaths worldwide. Ferroptosis, an iron-dependent form of programmed cell death, plays a key role in cancer immunotherapy. However, the role of immunity- and ferroptosis-related gene signatures in non-small cell lung cancer (NSCLC) remain unclear. Methods RNA-seq data and clinical information pertaining to NSCLC were collected from The Cancer Genome Atlas dataset. Univariate and multivariate Cox regression analyses were performed to identify ferroptosis-related genes. A receiver operating characteristic (ROC) model was established for sensitivity and specificity evaluation. Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed to explore the function roles of differentially expressed genes. Results A signature composed of five ferroptosis-related genes was established to stratify patients into high- and low-risk subgroups. In comparison with patients in the low-risk group, those in the high-risk one showed significantly poor overall survival in the training and validation cohorts (P < 0.05). Multivariate Cox regression analysis indicated risk score to be an independent predictor of overall survival (P < 0.01). Further, the 1-, 2-, and 3-year ROCs were 0.623 vs. 0.792 vs. 0.635, 0.644 vs. 0.792 vs. 0.634, and 0.631 vs. 0.641 vs. 0.666 in one training and two validation cohorts, respectively. Functional analysis revealed that immune-related pathways were enriched and associated with abnormal activation of immune cells. Conclusions We identified five immunity- and ferroptosis-related genes that may be involved in NSCLC progression and prognosis. Targeting ferroptosis-related genes seems to be an alternative to clinical therapy for NSCLC.

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Correlation between anemia before treatment with survival in patients with advanced non-small cell lung cancer

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.18211 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 18211-18211

Author(s):

S. R. Bella ◽

M. E. Richardet ◽

P. Gomez Storniolo ◽

P. Celiz ◽

A. Lingua ◽

...

Keyword(s):

Lung Cancer ◽

Overall Survival ◽

Regression Analysis ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Cox Regression ◽

Small Cell ◽

Hemoglobin Level ◽

Small Cell Lung ◽

Cox Regression Analysis

18211 Background: Prognostic factors identified in advanced non small cell lung cancer are: age, gender, PS, h. SWOG univariable analysis in patients with chemotheraphy; confirmed these factors and show a relationship between the hemoglobin level and the overall survival; in addition the metastasic site number and cisplatin- based chemotheraphy (7). To analyse and compare the hemoglobin level before cisplatin- based chemotheraphy with survival in patients with advanced non- small cell lung cancer. Methods: Retrospective study conducted at the IONC of the 179 clinical record were analized, over a 5 year period. The collected data were: age, gender, PS, histologic type, stage, chemotheraphy cycles number, smooke history, number and metastasic site. We analyzed median and overal survival using Kaplan Meier, and the anemia as a prognostic implication factor with univariable and multivariable Cox regression analysis. Istologic type and TNM (1–6). Results: The mean age was 59 (40–79); 146 (81.5%) male and 33 (18.5%) women; histological types found were squamous cell carcinomas in 66 (37%), and adenocarcinoma in 113 (63%); stage IIIB in 61 (34%) and IV in 118 (66%). 147 (82%) were smokers and 32 (18%) were never smokers. All the patients had PS 0–1. Median overall survival time was 11.53 months and 13.88 months in the haemoglobin level < or > 11 gr/ 100 ml, respectively. (p=0.3). In univariable Cox regression analysis, smoking rates and chemotheraphy cycles number were predictors of survival (p=0.05 y p=0.018, respectively). Hemoglobine (p=0.55). In multivariable Cox regression analysis, only the number of cycles was predictor of survival (p=0.026). Hemoglobine (p=0.34). Conclusions: In our experience, a greater survival tendency was observed in patients with advanced non- small cell lung cancer who presented levels of Hemoglobine greater than 11 gr/dl, previous to cisplatin- based chemotherapy without statistical significance. [Table: see text]

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Prognostic factors of oligometastatic non-small-cell lung cancer following radical therapy: a multicentre analysis

European Journal of Cardio-Thoracic Surgery ◽

10.1093/ejcts/ezz384 ◽

2020 ◽

Vol 57 (6) ◽

pp. 1166-1172 ◽

Cited By ~ 2

Author(s):

Isabelle Opitz ◽

Miriam Patella ◽

Loic Payrard ◽

Jean Yannis Perentes ◽

Rolf Inderbitzi ◽

...

Keyword(s):

Lung Cancer ◽

Overall Survival ◽

Prognostic Factors ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Cox Regression ◽

Small Cell ◽

Small Cell Lung ◽

Curative Intent ◽

Cox Regression Analysis

Abstract OBJECTIVES Patients with oligometastatic non-small-cell lung cancer (NSCLC) may benefit from therapy with curative intent. Our goal was to identify prognostic factors related to better prognosis in a multicentre analysis of patients who underwent surgery of primary tumours in combination with radical treatment of all metastatic sites. METHODS We retrospectively reviewed the records of oligometastatic patients who underwent resection of primary tumours at 4 centres (August 2001–February 2018). Oligometastasis was defined as ≤5 synchronous metastases in ≤2 organs. Radical metastatic treatment was surgery, radiotherapy or a combination. The Cox proportional hazards model was used for identification of prognostic factors on overall survival. RESULTS We treated 124 patients; 72 (58%) were men, mean age 60 ± 9.8 years, with 87 (70%) adenocarcinoma. Sixty-seven (54%) patients had positive pathologic-N stage (pN). Brain metastases were most common (n = 76; 61%) followed by adrenal (n = 13; 10%) and bone (n = 12; 10%). Systemic therapy was administered in 101 (82%) patients. Median follow-up was 60 months [95% confidence interval (CI) 41–86]. Thirty- and 90-day mortality rates were 0 and 2.4%, respectively. One-, 2-, and 5-year overall survival were 80%, 58% and 36%, respectively. Cox regression analysis showed that patients ≤60 years [hazard ratio (HR) 0.41, 95% CI 0.24, 0.69; P = 0.001] and patients with pN0 (HR 0.38, 95% CI 0.21–0.69; P = 0.002) had a significant survival benefit. The presence of bone metastases negatively affected survival (HR 2.53, 95% CI 1.05–6.09; P = 0.04). CONCLUSIONS Treatment with curative intent of selected oligometastatic NSCLC, including resection of the primary tumour, can be performed safely and with excellent 5-year survival rates, especially in younger patients with pN0 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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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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Metastatic Lymph Node Station Number Predicts Survival in Small Cell Lung Cancer

10.1101/2020.09.06.20189191 ◽

2020 ◽

Author(s):

Zhang Han ◽

Jiang Cong ◽

Jin Kaiqi ◽

Zhang Jing ◽

Chen Yan ◽

...

Keyword(s):

Lung Cancer ◽

Lymph Node ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Cox Regression ◽

Metastatic Lymph Node ◽

Small Cell ◽

Small Cell Lung ◽

Cox Regression Analysis ◽

Metastatic Lymph

Purpose: As for pathologic N category, various regrouping strategies have been raised in non small cell lung cancer (NSCLC) but little was done in small cell lung cancer (SCLC). On the basis of the suggestions discussed in NSCLC, we proposed a novel, metastatic lymph node station number (MNSN) based pathologic N parameter and compared its efficacy in predicting survival with pN in SCLC. Methods: We retrospectively analyzed the patients operated and pathologically diagnosed as SCLC in our hospital between 2009 and 2019. Kaplan Meier method and Cox regression analysis were used to compare survival between groups defined by pN and MNSN. Results: From 2009 to 2019, 566 patients received surgery for SCLC and 530 of them were eligible for subsequent analysis, with a median followup time of 21 months. The 5-year overall survival (OS) rates were 58.8%, 38.6%, 27.9% for pN0, pN1, pN2 stages and were 58.8%, 36.8%, 22.1%, 0% for MNSN0, 1-2, 3-5, 6-7 groups, respectively. Analyses of overall and recurrence-free survival (RFS) revealed that pN1 could not be distinguished from pN2 (OS, p=0.099; RFS, p=0.254), but the groups in MNSN were well separated from each other (OS, p<0.001, p=0.001, p=0.063; RFS, p<0.001, p=0.026, p=0.01, compared with the former group). When adjusted for sex, age, smoking, tumor purity and T stage, MNSN groups were independent hazard factors for OS and RFS.

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Surgery as primary treatment for limited disease small cell lung cancer: Time to re-evaluate

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.7719 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 7719-7719

Author(s):

E. Lim ◽

P. Goldstraw

Keyword(s):

Lung Cancer ◽

Overall Survival ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Cox Regression ◽

Complete Resection ◽

Small Cell ◽

Prognostic Impact ◽

Small Cell Lung ◽

Limited Disease

7719 Background: Chemoradiation is considered the gold standard for the management of limited disease (LD) small cell lung cancer (SCLC). Surgery has been abandoned due to poor overall survival, but many small series report good results with selected extremely limited disease (in one study without adjuvant treatment). Controversy remains if and when surgery should be considered as a primary modality. We sought to determine the survival and impact of pathologic staging in patients after complete resection of SCLC and the prognostic impact of pathologic stage. Methods: A retrospective review was undertaken of patients who underwent surgery between 1980 and 2003. Patients were staged according to the 6th UICC revision, actuarial survival estimated with Kaplan Meier methods and comparisons were undertaken using Cox regression. Results: We identified 51 patients who underwent complete resection with systematic nodal dissection for SCLC. The mean age (SD) was 61 (11) years and 37 (73%) were men. Complete staging information was available in 47, listed by stage with IA (n=6), IB (n=10), IIA (n=5), IIB (n=15), IIIA (n=10), IIIB (n=1). The median time to follow up (1st to 3rd quartile) was 4.5 (1.3 to 11.9) years with an overall survival (95% CI) at 1 and 5 years of 82% (72, 93) and 61% (48, 76). There were no clear differences in the outcome of patients in T categories 1 and 2 (P=0.411) with good overall results in patients across the spectrum of nodal disease from N0 to N2 (P=0.281). Conclusions: This study shows excellent survival for stage I to III patients who underwent lung resection with complete nodal resection for SCLC. These results, in an era of improved pre-operative and intra-operative staging, suggests that TNM staging is relevant in extremely limited disease SCLC and suggest that the role of surgery in such cases should be re- evaluated. No significant financial relationships to disclose.

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A randomized trial in inoperable non-small-cell lung cancer: vindesine and cisplatin versus mitomycin, vindesine, and cisplatin versus etoposide and cisplatin alternating with vindesine and mitomycin.

Journal of Clinical Oncology ◽

10.1200/jco.1991.9.4.606 ◽

1991 ◽

Vol 9 (4) ◽

pp. 606-613 ◽

Cited By ~ 42

Author(s):

M Fukuoka ◽

N Masuda ◽

K Furuse ◽

S Negoro ◽

M Takada ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Response Rate ◽

Cox Regression ◽

Performance Status ◽

Small Cell ◽

Survival Times ◽

Small Cell Lung ◽

Cox Regression Analysis

Patients with inoperable non-small-cell lung cancer (NSCLC) were randomly assigned to receive one of three dosage regimens: (1) vindesine and cisplatin (VP); (2) mitomycin, vindesine, and cisplatin (MVP); or (3) etoposide and cisplatin alternating with vindesine and mitomycin (EP/VM). In 199 assessable patients, the response rates were VP, 33%; MVP, 43%; and EP/VM, 19%. The addition of mitomycin to the VP regimen did not significantly improve the response rate. The response rate was significantly lower with the EP/VM regimen than with the MVP regimen (P less than .01). The median survival times were VP, 50 weeks; MVP, 42 weeks; and EP/VM, 40 weeks. These differences were not significant. Grade III or IV thrombocytopenia was significantly greater (P less than .01) in MVP patients (22%) than in the VP (5%). Other toxicities were similar in the three groups. Analyses of prognostic factors showed that treatment with MVP, sex, and histologic classification (squamous cell carcinoma) were predictive of improved response. Important factors for improved survival, according to the Cox regression analysis, were the stage of disease, performance status, sex, weight loss before diagnosis, and hemoglobin concentration.

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Molecular Identification of Immunity- and Ferroptosis-related Gene Signature in Non-small Cell Lung Cancer

10.21203/rs.3.rs-390478/v1 ◽

2021 ◽

Author(s):

Taisheng Liu ◽

Jinye Zhang ◽

Xiaoshan Hu ◽

Tao Xie ◽

Jian Zhang

Keyword(s):

Lung Cancer ◽

Overall Survival ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Risk Group ◽

Risk Groups ◽

Gene Signature ◽

Small Cell ◽

Related Gene ◽

Small Cell Lung

Abstract Background: Lung cancer is one of the dominant causes of cancer-related deaths worldwide. Ferroptosis, an iron-dependent regulated cell death, plays an important role in the cancer immunotherapy. However, the role of immunity- and ferroptosis-related gene signature in non-small cell lung cancer (NSCLC) remains unknown.Method: The RNA sequencing (RNA-seq) expression data and clinical information of NSCLC were downloaded from The Cancer Genome Atlas (TCGA) database and performed differential analysis. Univariate and multivariate cox regressions were used to identify the ferroptosis-related gene, and receiver operating characteristic (ROC) model was established using the independent risk factors. GO and KEGG enrichment analyses were performed to investigate the biological functions of differential genes.Results: A 5-gene signature was constructed to stratify patients into high- and low-risk groups. Compared with patients in the low-risk group, patients in the high-risk group showed significantly poor overall survival (P < 0.001 in the TCGA cohort and P = 0.001 in the GSE13213 cohort). The risk score was an independent predictor for overall survival in multivariate Cox regression analyses (HR > 1, P < 0.01). The 1 year-, 2 year- and 3 year-ROCs were 0.792, 0.644 and 0.641 in TCGA and 0.623, 0.636 and 0.631 in GSE13213, respectively. Functional analysis revealed that immune-related pathways were enriched, and immune status were different between two risk groups. Conclusions: We identified differently expressed immunity- and ferroptosis-related genes that may involve in NSCLC. These genes may predict the overall survival in NSCLC and targeting ferroptosis may be an alternative for clinical therapy.

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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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A fourteen-lncRNA risk score system for prognostic prediction of patients with non-small cell lung cancer

Cancer Biomarkers ◽

10.3233/cbm-190505 ◽

2020 ◽

Vol 29 (4) ◽

pp. 493-508

Author(s):

Jia-Yi Song ◽

Xiao-Ping Li ◽

Xiu-Jiao Qin ◽

Jing-Dong Zhang ◽

Jian-Yu Zhao ◽

...

Keyword(s):

Lung Cancer ◽

Overall Survival ◽

Small Cell Lung Cancer ◽

Risk Score ◽

Cell Lung Cancer ◽

Small Cell ◽

Small Cell Lung ◽

Cox Regression Analysis ◽

Score Model ◽

Nsclc Patients

Growing evidence has underscored long non-coding RNAs (lncRNAs) serving as potential biomarkers for cancer prognosis. However, systematic tracking of a lncRNA signature for prognosis prediction in non-small cell lung cancer (NSCLC) has not been accomplished yet. Here, comprehensive analysis with differential gene expression analysis, univariate and multivariate Cox regression analysis based on The Cancer Genome Atlas (TCGA) database was performed to identify the lncRNA signature for prediction of the overall survival of NSCLC patients. A risk-score model based on a 14-lncRNA signature was identified, which could classify patients into high-risk and low-risk groups and show poor and improved outcomes, respectively. The receiver operating characteristic (ROC) curve revealed that the risk-score model has good performance with high AUC value. Multivariate Cox’s regression model and stratified analysis indicated that the risk-score was independent of other clinicopathological prognostic factors. Furthermore, the risk-score model was competent for the prediction of metastasis-free survival in NSCLC patients. Moreover, the risk-score model was applicable for prediction of the overall survival in the other 30 caner types of TCGA. Our study highlighted the significant implications of lncRNAs as prognostic predictors in NSCLC. We hope the lncRNA signature could contribute to personalized therapy decisions in the future.

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