scholarly journals High PD-L1/IDO-2 and PD-L2/IDO-1 Co-Expression Levels Are Associated with Worse Overall Survival in Resected Non-Small Cell Lung Cancer Patients

Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 273
Author(s):  
Vienna Ludovini ◽  
Fortunato Bianconi ◽  
Annamaria Siggillino ◽  
Jacopo Vannucci ◽  
Sara Baglivo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Early Stage ◽  
Small Cell ◽  
Small Cell Lung ◽  
Expression Levels ◽  
Immune Related Genes ◽  
Gene Expression Levels

Programmed death ligand 1 (PD-L1) expression is a predictive biomarker of the success of PD-1/PD-L1 inhibitor therapy for patients with advanced non-small cell lung cancer (NSCLC) but its role as a prognostic marker for early-stage resectable NSCLC remains unclear. We studied gene expression levels of immune-related genes PD-1, PD-L1, PD-L2, IDO-1, IDO-2 and INFγ in tumor tissue of surgically resected NSCLC and correlated the finding with clinicopathological features and patient outcomes. A total of 191 consecutive early-stage NSCLC patients who underwent curative pulmonary resection were studied. The mRNA expression levels of immune-related genes were evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) using RT2 Profiler PCR Arrays (Qiagen). PD-1, PD-L2 and IDO-2 gene expression levels were significantly higher in patients with squamous histology (p = 0.001, p = 0.021 and p < 0.001; respectively). PD-1, PD-L1 and IDO-2 gene expression levels were significantly higher in patients with higher stage (p = 0.005, p = 0.048 and p = 0.002, respectively). The univariate analysis for recurrence-free survival (RFS) and overall survival (OS) showed that patients with higher levels of three-genes (PD-L1/PD-L2/INFγ) (hazard ratio (HR)) 1.90 (95% confidence interval (CI), 1.13–3.21), p = 0.015) were associated with a worse RFS, while patients with higher levels of both genes (PD-L1/IDO-2) or (PD-L2/IDO-1) were associated with a worse OS (HR 1.63 95% CI, 1.06–2.51, p = 0.024; HR 1.54 95% CI, 1.02–2.33, p = 0.04; respectively). The multivariate interaction model adjusted for histology and stage confirmed that higher levels of three genes (PD-L1/PD-L2/INFγ) were significantly associated with worse RFS (HR 1.98, p = 0.031) and higher levels of both genes (PD-L1/IDO-2) and (PD-L2/IDO-1) with worse OS (HR 1.98, p = 0.042, HR 1.92, p = 0.022). PD-L1/IDO-2 and PD-L2/IDO-1 co-expression high levels are independent negative prognostic factors for survival in early NSCLC. These features may have important implications for future immune-checkpoint therapeutic approaches.

scholarly journals Predicting brain metastasis in early stage non-small cell lung cancer patients by gene expression profiling

2020 ◽  
Vol 9 (3) ◽  
pp. 682-692
Author(s):  
Iris Kamer ◽  
Yael Steuerman ◽  
Inbal Daniel-Meshulam ◽  
Gili Perry ◽  
Shai Izraeli ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Brain Metastasis ◽  
Small Cell Lung Cancer ◽  
Cancer Patients ◽  
Expression Profiling ◽  
Early Stage ◽  
Small Cell ◽  
Small Cell Lung ◽  
Lung Cancer Patients

A twenty eight-gene signature and survival in completely-resected non-small cell lung cancer (NSCLC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 10583-10583
Author(s):  
N. Van Zandwijk
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Gene Signature ◽  
Small Cell ◽  
Risk Scores ◽  
Small Cell Lung ◽  
Independent Validation

10583 Background: Current staging methods are imprecise for predicting the outcome of treatment of non-small-cell lung cancer (NSCLC). We have developed a 28-gene signature that is closely associated with recurrence-free and overall survival. Methods: We used whole-genome gene expression microarrays to analyze frozen-tumor samples from 174 patients (pT1&2, N0&1, MO), who had undergone complete surgical resection in 5 European institutions. Randomly generated numbers were used to assign 2/3 of the samples to an algorithm training group with the remaining 1/3 set aside for independent validation. Cox proportional hazards models were used to evaluate the association between the level of expression and patient survival. We used risk scores and nearest centroid analysis to develop a gene-expression model for the prediction of treatment outcome. Leave-one-out cross validation was used to prevent model over-training. Results: 28 genes that correlated with survival were identified by analyzing microarray data and risk scores. Based on the expression of these genes, patients in training and validation groups were classified as either high (48%) or low (52%) risk. Analysis of predicted risk groups revealed significantly different survival distributions for patients in both the training set (p<0.001) and independent validation set (p=0.006). Genes in our prognostic signature encode for several membrane-bound proteins with previously demonstrated involvement in cell cycle regulation and cell proliferation processes. Conclusions: Our 28-gene signature is closely associated with time to recurrence and overall survival of completely-resected NSCLC patients. [Table: see text]

scholarly journals Epigenetic Suppression of the T-box Subfamily 2 (TBX2) in Human Non-Small Cell Lung Cancer

2019 ◽  
Vol 20 (5) ◽  
pp. 1159 ◽  
Author(s):  
Eliana Nehme ◽  
Zahraa Rahal ◽  
Ansam Sinjab ◽  
Athar Khalil ◽  
Hassan Chami ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Normal Lung ◽  
Small Cell Lung ◽  
Alveolar Cells ◽  
Expression Levels ◽  
Human Nsclc

(1) The TBX2 subfamily of transcription factors (TBXs 2, 3, 4 and 5) are markedly down-regulated in human non-small cell lung cancer (NSCLC) and exert tumor suppressor effects in lung malignancy. Yet, mechanisms underlying suppressed expression of the TBX2 subfamily in NSCLC are elusive. Here, we interrogated probable epigenetic mechanisms in suppressed expression of the TBX2 subfamily in human NSCLC. (2) TBX2 subfamily gene expression and methylation levels in NSCLC and normal lung tissues were surveyed using publicly available RNA-sequence and genome-wide methylation datasets. Methylation β-values of the four genes were statistically compared between NSCLCs and normal lung tissues, correlated with gene expression levels, and interrogated with clinicopathological variables. Expression and methylation levels of TBXs were quantified in NSCLC cells using real-time PCR and methylation-specific PCR assays, respectively. Effects of the DNA methyltransferase inhibitor 5-azacytidine (Aza) on TBX2 subfamily expression were assessed in NSCLC cells. Impact of TBX2 subfamily expression on Aza-treated cells was evaluated by RNA interference. (3) All four TBXs were significantly hypermethylated in NSCLCs relative to normal lung tissues (p < 0.05). Methylation β-values of the genes, with exception of TBX2, were significantly inversely correlated with corresponding mRNA expression levels (p < 0.05). We found no statistically significant differences in hypermethylation levels of the TBX2 subfamily by clinicopathological features including stage and tobacco history. Expression levels of the TBX genes were overall suppressed in NSCLC cells relative to normal alveolar cells. Members of the subfamily were significantly hypermethylated in all tested NSCLC cell lines relative to normal alveolar cells. Treatment with Aza induced the expression of the TBX2 subfamily concomitant with NSCLC cell growth inhibition. Further, simultaneous knockdown of the four TBX genes markedly reduced anti-growth effects of Aza in NSCLC cells. (4) Our study sheds light on new epigenetic profiles in the molecular pathogenesis of human NSCLC.

Investigating gene expression profile of non-small cell lung cancer

Open Medicine ◽  
2011 ◽  
Vol 6 (5) ◽  
pp. 608-615
Author(s):  
Tõnu Vooder ◽  
Andres Metspalu
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Survival Rate ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Early Stage ◽  
Treatment Strategies ◽  
Small Cell ◽  
Small Cell Lung ◽  
Lung Cancers

AbstractLung cancer is mainly a lifestyle-associated disease with poor prognosis and the lowest five year survival rate of all types of cancer. Lung cancers are divided into two main groups: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Surgical treatment is generally indicated in cases of early stage NSCLC, and those patients treated with radical and aggressive surgery have a somewhat better survival rate. The main problems with lung cancer treatment are due to late diagnosis, rapidly developing drug resistance and side effects of the treatment that are experienced by almost all patients. The next step for distinguishing histologically complicated lung cancers and determining optimal treatment strategies is gene expression analysis. Supported by gene expression data, it is possible to prognosticate the course of the disease.

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