Prognostic value of nonangiogenic and angiogenic growth patterns in non-small-cell lung cancer.
Ontology highlight
ABSTRACT:
SUBMITTER: Sardari Nia P
PROVIDER: S-EPMC2409915 | biostudies-other | 2004 Oct
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Transglutaminase 2 (TG2) plays important roles in cell survival and cancer progression. In this study, we examined TG2 expression in specimen of 194 patients diagnosed with non-small cell lung cancer (NSCLC), and found that the TG2 gene expression was significantly higher in lung cancer tissues as compared to paired incisal marginal tissues or normal tissues. Our data revealed that patients with lower level of TG2 expression detected in cancer tissues had longer disease free survival and overall survival as compared to the patients with higher TG2 expression. We also found that TG2 expression level correlated to NSCLC recurrence. These results suggest a potential prognosis impact of TG2 for NSCLC patients.
| S-EPMC5542209 | biostudies-other
Project description:Introduction: Accumulating evidence showed that a large number of microRNAs (miRNAs) are abnormally expressed in lung cancer tissues and play critical roles in cancer development and progression. The aim of this study is to identify the differentially expressed miRNAs (DEMs) between non-small cell lung cancer (NSCLC) and normal lung tissues, and evaluate the prognostic value and potential target gene functional enrichment of the DEMs. Materials and Methods: We first downloaded the high-throughput miRNA data from The Cancer Genome Atlas Project (TCGA) database, and subsequently analyzed the data using bioinformatics analysis including limma package in R, Kaplan-Meier curve and Log-rank method, and several online analysis tools. Results: A total of 125 DEMs and 138 DEMs were respectively identified in lung adenocarcinoma (LUAD) tissues and lung squamous cell carcinoma (LUSC) tissues compared with their matched normal tissues. Moreover, we found that the prognostic function of the eight miRNAs (miR-375, miR-148a, miR-29b-1 and miR-584 for LUAD; miR-4746, miR-326, miR-93 and miR-671 for LUSC). Furthermore, the two four-miRNA signatures were constructed and found to be an independent prognostic factor for LUAD and LUSC patients, respectively. Additionally, our results indicated that the target genes of eight miRNAs may be involved in various pathways related to NSCLC, including PI3K-Akt, TGF-beta, FoxO, Ras, GPI-anchor biosynthesis and metabolic, Rap1, HIF-1 and proteasome. Conclusion: Overall, eight miRNAs were closely correlated with survival of NSCLC patients, and the constructed two four-miRNA signatures could be respectively used as prognostic markers in LUAD and LUSC patients.
| S-EPMC6843868 | biostudies-literature
Project description:Recent progress in cancer biology has led to the discovery of increasing number of oncogene alterations that have dramatically changed the paradigm of lung cancer treatment. MET is a tyrosine kinase receptor for the hepatocyte growth factor (HGF) that is deregulated in several malignancies, including non-small cell lung cancer (NSCLC). Abnormal MET-HGF signaling pathway activation can occur via different mechanisms, including HGF and/or MET overexpression, MET gene amplification, mutations or rearrangements. MET protein overexpression and increased MET gene number have been identified as poor prognostic factors in several series of surgically resected NSCLC making this receptor an attractive target for cancer treatment. Several clinical trials have recently evaluated the activity of a variety of anti-MET strategies in NSCLC patients with or without molecular selection with a variable degree of success, underscoring the need of establishing the best predictive biomarker for the identification of responding patients.
| S-EPMC4416957 | biostudies-literature
Project description:BackgroundAbout 50% of non-small cell lung cancer (NSCLC) patients develop distant metastases following pulmonary resection. Currently, there are no reliable factors allowing for individual selection of high-risk patients for adjuvant systemic therapies.MethodsWe assessed by quantitative reverse transcription PCR microRNA (miRNA) expression in 273 stage I-IIIA NSCLC samples. Expression of 677 miRNAs was evaluated in fresh-frozen tumour samples in the training cohort of 50 squamous cell carcinoma (SCC) patients who underwent curative surgery. Of those, 20 patients developed distant metastases, and 30 were free of recurrence for >4 years. In the second step, miRNAs with highest predictive value for distant relapse were re-evaluated in formalin-fixed paraffin-embedded material in an independent group of 134 stage I-IIIA SCC patients. Additionally, the same miRNAs were investigated in 89 lung adenocarcinoma (AC) patients and in normal lung parenchyma (NLP).ResultsIn the training cohort of SCC, six miRNAs were differently expressed in the non-recurrent vs recurrent groups and correlated with distant recurrence-free survival, however none reached the level of significance after correction for multiple testing. Of these six miRNAs, miR-662, -192 and -192* were confirmed as prognostic in the independent SCC cohort. Expression of miR-128, -10b, -502-3p and -192 differed between SCC and AC, and miR-128 and -192 - between NLP and NSCLC.ConclusionsWe identified three new miRNAs predictive of distant relapse in operable SCC. Future miRNA studies should account for differences between NSCLC subtypes.
| S-EPMC3929871 | biostudies-literature
Project description:BackgroundCirculating tumor DNA (ctDNA) levels correlate well with tumor bulk. In this paper we aim to estimate the prognostic value of the dynamic quantification of ctDNA levels.Materials and methodsA total of 251 serial plasma samples from 41 non-small-cell lung cancer patients who carried an activating EGFR mutation were analysed by digital PCR. For survival analysis, ctDNA levels were computed as a time-dependent covariate.ResultsDynamic ctDNA measurements had prognostic significance (hazard ratio for overall survival and progression free survival according to p.T790M mutant allele frequency; 2.676 and 2.71 respectively; P < 0.05). In the same way, patients with p.T790M-negative or unchanging or decreasing plasma levels of sensitizing EGFR mutation were 12 and 4.8 times more likely to maintain response or stable disease, respectively, than patients in which the opposite occurred (P < 0.05).On average, the p.T790M mutation was detected in plasma 51 days before the assessment of progression disease by CT-scan. Finally, ctDNA outperformed CTCs for assessing tumor progression (P = 0.021).ConclusionsThe appearance or increase in a unit of the p.T790M allele frequency almost triples the risk of death and progression. This information can be used to design clinical trials aiming to estimate whether T790M positive patients should start second line treatment based on molecular data rather than imaging data.
| S-EPMC5787483 | biostudies-literature
Project description:ImportancePrevious studies have suggested the importance of the baseline derived neutrophil to lymphocyte ratio (dNLR) and lactate dehydrogenase (LDH) level as prognostic markers. The lung immune prognostic index (LIPI) was shown to be associated with progression-free survival (PFS) and overall survival (OS) among patients with metastatic non-small cell lung cancer (mNSCLC) treated with immune checkpoint inhibitors (ICIs) but not cytotoxic chemotherapy (CCT).ObjectiveTo determine whether the LIPI is associated with long-term outcomes in pooled analyses of clinical studies of ICI and targeted therapy (TT) for patients with mNSCLC.Design, setting, and participantsAn exploratory pooled analysis was performed of the LIPI on data from 11 randomized clinical multinational trials evaluating ICIs and TT submitted to the US Food and Drug Administration between January 1, 2013, and December 31, 2017, for 4914 patients with mNSCLC. Lung immune prognostic index scores were calculated based on the dNLR and the LDH level per previous publications to generate good, intermediate, and poor composite scores. Multivariable Cox proportional PFS and OS hazard ratios were generated for the dNLR, the LDH level, age, smoking status, histologic characteristics, and Eastern Cooperative Oncology Group performance score.Main outcomes and measuresOverall survival and PFS and their association with good, intermediate, or poor prognostic LIPI scores.ResultsEleven mNSCLC randomized trials were analyzed, including 3987 patients with available data. In 5 ICI trials comprising 2440 patients, 1368 patients received ICIs and 1072 patients received CCT. In 6 TT trials comprising 1547 patients, 1110 patients received TT and 437 patients received CCT. A good LIPI score was associated with better OS among patients receiving ICIs (hazard ratio, 0.34; 95% CI, 0.28-0.42), TT (hazard ratio, 0.28; 95% CI, 0.21-0.37), and CCT (hazard ratio, 0.49; 95% CI, 0.40-0.60 in ICI trials; hazard ratio, 0.41; 95% CI, 0.27-0.61 in TT trials) than those with poor LIPI scores. Similar findings were observed in terms of PFS (ICIs: hazard ratio, 0.59; 95% CI, 0.48-0.72; TT: hazard ratio, 0.46; 95% CI, 0.37-0.57; and CCT: hazard ratio, 0.56; 95% CI, 0.45-0.68 in ICI trials; hazard ratio, 0.51; 95% CI, 0.38-0.69 in TT trials).Conclusions and relevanceThe baseline LDH level and dNLR are important prognostic biomarkers irrespective of treatment modality for patients with mNSCLC. As further prospective clinical trial information is collected, the role of the LIPI score can be better defined.
| S-EPMC6659150 | biostudies-literature
Project description:Non-small cell lung carcinoma (NSCLC) is the most common form of lung cancer and is associated with a high mortality rate worldwide. The majority of individuals bearing NSCLC are treated with surgery plus adjuvant cisplatin, an initially effective therapeutic regimen that, however, is unable to prevent relapse within 5 years after tumor resection in an elevated proportion of patients. The factors that predict the clinical course of NSCLC and its sensitivity to therapy remain largely obscure. One notable exception is provided by pyridoxal kinase (PDXK), the enzyme that generates the bioactive form of vitamin B6. PDXK has recently been shown to be required for optimal cisplatin responses in vitro and in vivo and to constitute a bona fide prognostic marker in the NSCLC setting. Together with PDXK, 84 additional factors were identified that influence the response of NSCLC cells to cisplatin, in vitro including the hepatic lipase LIPC. Here, we report that the intratumoral levels of LIPC, as assessed by immunohistochemistry in two independent cohorts of NSCLC patients, positively correlate with disease outcome. In one out of two cohorts studied, the overall survival of NSCLC patients bearing LIPChigh lesions was unaffected, if not slightly worsened, by cisplatin-based adjuvant therapy. Conversely, the overall survival of patients with LIPClow lesions was prolonged by post-operative cisplatin. Pending validation in appropriate clinical series, these results suggest that LIPClow NSCLC patients would be those who mainly benefit from adjuvant cisplatin therapy. Thus, the expression levels of LIPC appear to have an independent prognostic value (and perhaps a predictive potential) in the setting of NSCLC. If these findings were confirmed by additional studies, LIPC expression levels might allow not only for NSCLC patient stratification, but also for the implementation of personalized therapeutic approaches.
| S-EPMC3594265 | biostudies-literature
Project description:IntroductionTargeting activating oncogenic driver mutations in lung adenocarcinoma has led to prolonged survival in patients harboring these specific genetic alterations. The prognostic value of these mutations has not yet been elucidated. The prevalence of recently uncovered non-coding somatic mutation in promoter region of TERT gene is also to be validated in lung cancer. The purpose of this study is to show the prevalence, association with clinicalpathological features and prognostic value of these factors.MethodsIn a cohort of patients with non-small cell lung cancer (NSCLC) (n = 174, including 107 lung adenocarcinoma and 67 lung squamous cell carcinoma), EGFR, KRAS, HER2 and BRAF were directly sequenced in lung adeoncarcinoma, ALK fusions were screened using FISH (Fluorescence in situ Hybridization).TERT promoter region was sequenced in all of the 174 NSCLC samples. Associations of these somatic mutations and clinicopathological features, as well as prognostic factors were evaluated.ResultsEGFR, KRAS, HER2, BRAF mutation and ALK fusion were mutated in 25.2%, 6.5%, 1.9%, 0.9% and 3.7% of lung adenocarcinomas. No TERT promoter mutation was validated by reverse-sided sequencing. Lung adenocarcinoma with EGFR and KRAS mutations showed no significant difference in Disease-free Survival (DFS) and Overall Survival (OS). Cox Multi-variate analysis revealed that only N stage and HER2 mutation were independent predictors of worse overall survival (HR = 1.653, 95% CI 1.219-2.241, P = 0.001; HR = 12.344, 95% CI 2.615-58.275, P = 0.002).ConclusionsWe have further confirmed that TERT promoter mutation may only exist in a very small fraction of NSCLCs. These results indicate that dividing lung adenocarcinoma into molecular subtypes according to oncogenic driver mutations doesn't predict survival difference of the disease.
| S-EPMC4157862 | biostudies-literature
Project description:Clinical implications of KRAS mutations in advanced non-small cell lung cancer remain unclear. We retrospectively evaluated the prognostic and predictive value of KRAS mutations in patients with advanced NSCLC. Among 484 patients with available results for both KRAS and EGFR mutations, 39 (8%) had KRAS and 182 (38%) EGFR mutations, with two cases having both mutations. The median overall survivals for patients with KRAS mutations, EGFR mutations, or both wild types were 7.7, 38.0, and 15.0 months, respectively (P<0.001). The KRAS mutation was an independent poor prognostic factor in the multivariate analysis (hazard ratio?=?2.6, 95% CI: 1.8-3.7). Response rates and progression-free survival (PFS) for the pemetrexed-based regimen in the KRAS mutation group were 14% and 2.1 months, inferior to those (28% and 3.9 months) in the KRAS wild type group. KRAS mutation tended to be associated with inferior treatment outcomes after gemcitabine-based chemotherapy, while there was no difference regarding taxane-based regimen. Although the clinical outcomes to EGFR tyrosine kinase inhibitors (TKIs) seemed to be better in patients with KRAS wild type than those with KRAS mutations, there was no statistical difference in response rates and PFS according to KRAS mutation status when EGFR mutation status was considered. Two patients with both KRAS and EGFR mutations showed partial response to EGFR TKIs. Although G12D mutation appeared more frequently in never smokers, there was no difference in clinical outcomes according to KRAS genotypes. These results suggested KRAS mutations have an independent prognostic value but a limited predictive role for EGFR TKIs or cytotoxic chemotherapy in advanced NSCLC.
| S-EPMC3665805 | biostudies-literature
Project description:E2F transcription factor 3 (E2F3) plays a vital role in the development of various types of cancer. To verify whether E2F3 is a suitable biomarker for the prognosis of lung cancer, bioinformatics analysis was performed to determine the differential expression level of E2F3 in lung cancer and the surrounding non-tumor tissues, and the results were confirmed in a NSCLC cell line and a tissue microarray (TMA). The relevance of E2F3 in non-small cell lung cancer (NSCLC) was investigated in 19 studies from the Oncomine database and confirmed in The Cancer Genome Atlas database. In the lung cancer cell line A549, the inhibition of E2F3 mRNA expression level led to decreased tumor cell viability and cell migration, which was determined by a Cell Counting Kit-8 and wound healing assays, respectively. Immunohistochemistry analyses of E2F3, Bcl-2, Bax and caspase-3 were performed in the NSCLC TMA (n=50). The assessment of TMA detected the increase of E2F3 protein expression level in the tumor tissues, as compared with that in the non-tumor tissues, which was also correlated with the increase in expression of Bcl-2 in tumors. Analysis of the clinical data from patients with NSCLC revealed that the overexpression of E2F3 was associated with early lymphatic spreading, and poor patient survival time. The OncomiR website was used to predict the E2F3 upstream microRNAs and determine their prognostic value in patients with NSCLC. The results from the present study revealed that E2F3 was overexpressed at both the transcriptional and translational levels in NSCLC tissues, as compared with that in non-tumor tissues. The overexpression of E2F3 was associated with the upregulation of the anti-apoptotic factor, Bcl-2, which may contribute to uncontrolled tumor growth. Thus, E2F3 was shown to have important oncogenic properties in the development of NSCLC, and it may become a potential biomarker for patients with NSCLC.
| S-EPMC8020386 | biostudies-literature