Prognostic significance of epigenetic regulatory gene expression in patients with non-small-cell lung cancer.
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ABSTRACT:
SUBMITTER: Tu Z
PROVIDER: S-EPMC7993691 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The majority of lung cancers belong to the non-small-cell lung cancer (NSCLC) category, which is linked to a high mortality rate despite significant progress in diagnosis and treatment. Therefore, there is a need for novel prognostic NSCLC biomarkers to improve prognosis which currently remains poor. Recent studies and analyses of gene expression data of NSCLC revealed that high expression of KIAA1522 was significantly associated with poor prognosis and decreased overall survival. We identified 98 patients who underwent radical curative surgical resections or metastasectomy for pulmonary adenocarcinoma and squamous cell carcinoma at our institution or the pathological diagnosis confirmed by our pathologists. Following the latest data, we utilized immunohistochemistry to assess the expression of KIAA1522 and investigated its association with various clinic-demographic parameters, pathological stages, recurrence rates, overall survival, and disease-free survival in patients who achieved complete remission. Notably, there were no significant differences in the expression profiles of KIAA1522 between adenocarcinoma and squamous cell carcinoma samples (p=0.6). Survival analysis was conducted using log-rank tests and a multivariate Cox proportional hazard model. Of the 98 samples, 54 (55.1%) exhibited high expression of KIAA1522, and patients with high KIAA1522 expression had a significantly shorter overall survival than the low-expression group (p=0.01). Multivariate Cox proportional hazard models in which metastatic patients were included revealed that along with older age, higher TNM stage (tumor, node, metastasis system), and Eastern Cooperative Oncology Group (ECOG) performance status, high expression of KIAA1522 served as an independent prognostic factor. A high expression profile was not significantly associated with relapses in those whose complete remission had been achieved. Still, those patients with high expression of KIAA1522 tended to exhibit a shorter disease-free survival rate. In conclusion, our findings suggest that KIAA1522 expression is an independent factor for predicting overall survival and may serve as a valuable prognostic indicator for relapse and disease-free survival in NSCLC patients.
| S-EPMC10517341 | biostudies-literature
Project description:The microenvironment of solid tumours is significant in cancer development and progression. The aim of this study was to determine periostin (POSTN) expression by cancer-associated fibroblasts (CAFs) in non-small-cell lung cancer (NSCLC), as well as to assess associations with clinicopathological factors and prognosis. Immunohistochemical analysis of POSTN expression was performed on NSCLC (N = 700) and non-malignant lung tissue (NMLT) (N = 110) using tissue microarrays. Laser capture microdissection (LCM) for isolation of stromal and cancer cells of NSCLC was employed, and subsequently, POSTN mRNA expression was detected by real-time PCR. Immunofluorescence reaction and colocalisation analysis were performed by confocal microscopy. Expression of POSTN in CAFs was significantly higher in NSCLC and in the adenocarcinoma (AC) and squamous cell carcinoma (SCC) subtypes compared to NMLT. POSTN expression in CAFs increased with clinical cancer stage, grades (G) of malignancy, and lymph node involvement in NSCLC. Higher POSTN expression in CAFs was an independent prognostic factor for overall survival (OS). LCM confirmed significantly higher POSTN mRNA expression in the stromal cells (CAFs) compared to the lung cancer cells. POSTN produced by CAFs might be crucial for NSCLC progression and can be an independent negative prognostic factor in NSCLC.
| S-EPMC7582720 | biostudies-literature
Project description:BackgroundThe ?2-Adrenergic receptor (?2-AR) is associated with tumor growth and progression. However, the clinical significance of ?2-AR expression in patients with non-small cell lung cancer (NSCLC) remains unclear.MethodsThree hundred twenty-eight patients with surgically resected NSCLC were retrospectively investigated. Tumor sections were stained by immunohistochemistry for assessing ?2-AR and Ki-67 expression and microvessel density (MVD), which was using CD34 levels.Results?2-AR was positively expressed in 27% of all patients, in 29% of adenocarcinoma (AC) patients, and in 24% of non-AC patients. In AC patients, ?2-AR expression was significantly correlated with lymphatic permeation (r=0.240; P<0.001), vascular invasion (r=0.239; P<0.001), and Ki-67 expression (r=0.175; P=0.009). However, this correlation was not observed in non-AC patients. Positive ?2-AR expression was identified as a negative predictor for worse outcomes in AC patients, particularly in those with stage I tumors. Multivariate analysis confirmed that ?2-AR expression was an independent factor for predicting poor progression-free survival in stage I AC patients (HR=2.220; 95% CI, 1.077-4.573; P=0.031).Conclusion?2-AR expression is an independent prognostic factor for early-stage AC patients.
| S-EPMC5126349 | biostudies-literature
Project description:Various studies examined the relationship between EZH2 overexpression with the clinical outcome in patients with non-small cell lung cancer (NSCLC), but yielded inconsistent results. Electronic databases updated to Dec 2014 were searched to find relevant studies. A meta-analysis was conducted with eligible studies which quantitatively evaluated the relationship between EZH2 overexpression and survival of patients with NSCLC Survival data were aggregated and quantitatively analyzed. We performed a meta-analysis of 10 studies (n = 1,695 patients) that evaluated the correlation between EZH2 overexpression and survival in patients with lung cancer. Combined hazard ratios suggested that EZH2 overexpression was associated with poor prognosis of overall survival (OS) (HR = 1.68, 95% CI: 1.42-1.93) in patients with lung cancer. In the stratified analysis, significantly risks were found among Asians (HR = 1.33, 95% CI: 1.62-1.70), lung adenocarcinoma patients (HR = 1.75, 95% CI: 1.38-2.52, in stage I NSCLC patients (HR = 2.51, 95% CI: 1.23-3.79), but not among Caucasians. EZH2 overexpression indicates a poor prognosis for patients with NSCLC, this effect appears also significant when the analysis is restricted in Asian population, lung AC and stage I patients, but not among Caucasians.
| S-EPMC4709684 | biostudies-other
Project description:Metastatic non-small cell lung cancer (NSCLC) continues to have a poor prognosis despite recent advances in both targeted radiotherapy methodologies such as stereotactic body radiotherapy (SBRT) and immunotherapies. The impact of location of metastatic disease in patients with NSCLC has not been investigated; we aimed to investigate this using the Surveillance, Epidemiology, and End Results (SEER) database.We included 39,910 patients from the SEER database treated for M1b NSCLC from 2010-2013. We identified patients with metastatic disease in the brain, lung, liver, and bone. We used Kaplan-Meier analyses and Cox proportional hazards models to assess the impact of varying sites of metastatic disease on overall survival (OS).Patients with disease coded as in the brain without other disease in the lung, liver, or bone had improved OS relative to all other comers with M1b disease (HR =0.84, 95% CI, 0.84-0.90, P<0.001). Likewise, patients with disease coded as in the bone without other disease in the lung, liver, or brain had improved OS relative to all other comers with M1b disease (HR =0.89, 95% CI, 0.86-0.92, P<0.001).This hypothesis-generating analysis suggests that patients with limited metastatic NSCLC to the bone or brain may particularly benefit from aggressive upfront therapies.
| S-EPMC5543004 | biostudies-other
Project description:BackgroundEpithelial cadherin (E-cadherin), a calcium-dependent cell-cell adhesion molecule, as an important adhesion and signaling pathway mediator plays key roles in the maintenance of tissue integrity. However, the available results of E-cadherin expression and its prognostic value on non-small cell lung cancer (NSCLC) remain controversial. Therefore, a meta-analysis of published studies investigating the prognostic value of E-cadherin expression and its association with clinicopathological characteristics with NSCLC was performed.MethodsA literature search via PubMed, EMBASE, and MEDLINE (Ovid) databases was conducted. Data from eligible studies were extracted. Statistical analysis was performed using STATA 12.0.ResultsA total of 2412 patients from 15 studies were included in the meta-analysis. The results showed that the pooled hazard ratio (HR) for overall survival was 0.55 (95% confidence interval [CI]: 0.44-0.69) by univariate analysis and 0.68 (95% CI: 0.43-1.08) by multivariate analysis. In addition, the results showed a significant association between E-cadherin expression and the presence of lymph node metastasis (odds ratio = 0.37, 95% CI=0.05-0.69, P = 0.001).ConclusionOur study showed that positive expression of E-cadherin was associated with a favorable prognosis in patients with NSCLC, and might act as an inhibition factor of metastasis. However, adequately designed prospective studies are required to confirm this finding.
| S-EPMC4567004 | biostudies-literature
Project description:Nuclear factor kappa B (NF-κB), a key nuclear transcription factor, is associated with prognosis in a variety of human cancers. However, the clinical value of NF-κB in non-small cell lung cancer (NSCLC) is still controversial. Therefore, the aim of this meta-analysis was to obtain an accurate evaluation of the relationship between NF-κB expression and survival prognosis of NSCLC patients based on published articles. PubMed, EMBASE and Web of Science databases were systematically searched for potential articles. A total of 1159 patients from 7 eligible studies comparing prognostic significance of NF-κB expression levels in NSCLC were included in our meta-analysis. I2 statistic and P value were performed to evaluate heterogeneity. The results of analysis were presented as hazard ratio (HR) or odds ratios (OR) with 95% confidence interval (95% CI). Subgroup analysis based on ethnicity of NSCLC patients and NF-kB cellular localization within cancer cells were conducted to illustrate the potential discrepancy. Significant heterogeneity was considered at I2>50% and P<0.05, and random-effects model was used. The combined results indicated that higher NF-κB expression was associated with shorter overall survival (OS) of NSCLC patients (HR = 2.78, 95% CI = 1.51-5.12, P = 0.001). Moreover, NF-κB expression was closely associated with tumor stage (HR = 0.32, 95% CI = 0.18-0.57, P<0.0001), lymph node metastasis (HR = 0.56, 95% CI = 0.38-0.83, P = 0.004) and 5-year OS for NSCLC patients (OR = 1.83, 95% CI = 1.02-3.31, P = 0.04). We conclude that NF-κB expression may be a potential unfavorable prognostic marker for NSCLC patients.
| S-EPMC5973575 | biostudies-literature
Project description:The utility of circulating tumor cells (CTCs) as prognostic biomarkers in non-small cell lung cancer (NSCLC) is inconclusive due to the limitations of current CTC detection methods. Using a novel high-efficiency detection method, we determined the ability of CTCs to predict survival and chemotherapeutic responses in NSCLC. In 127 patients with advanced NSCLC, CTCs were counted and analyzed at baseline and during follow-up. Median overall survival (OS) and progression-free survival (PFS) were longer in patients with baseline CTC counts <8 CTCs/3.2 mL (20.0 vs. 10.4 months [P = 0.009] and 7.2 vs. 5.5 months [P < 0.001], respectively). Patients with post-treatment increases in the CTC count had poorer OS and PFS than those without increases (12.0 vs. 13.3 months [P = 0.028] and 5.2 vs. 6.4 months [P = 0.022], respectively). There was no association between the baseline CTC count and chemotherapeutic response (P = 0.734). However, the rate of progressive disease in patients with and without post-treatment increases in the CTC count were 15.6% and 2.4% (P = 0.042), respectively. The baseline CTC count and the change in the CTC count during treatment were both valuable prognostic indicators for NSCLC.
| S-EPMC5689711 | biostudies-literature
Project description:Nuclear factor erythroid 2-related factor 2 (NRF2) functions as a transcription factor and regulates a wide array of antioxidant and stress-responsive genes. NRF2 has been widely implicated in different types of cancers, but only limited studies concerning the relationship between NRF2 expression and tumour invasion or prognosis in lung cancer. Therefore, we conducted a meta-analysis to determine the prognostic value of NRF2 in patients with non-small cell lung cancer (NSCLC). The relationship between NRF2 expression in NSCLC patients and clinicopathological features was also investigated. Overall survival (OS) and treatment response rate were evaluated using STATA software. Twenty eligible articles with 2530 lung cancer patients were included in this meta-analysis. The results revealed that high expression level of NRF2 was associated with pathologic distant metastasis (odds ratio (OR) = 2.64, 95% confidence interval (CI) 1.62-4.31; P < 0.001), lymph node metastasis (OR = 2.14, 95% CI: 1.53-3.00; P < 0.001), and tumour node metastasis (TNM) stage (OR = 1.95, 95% CI: 1.52-2.49, P < 0.001). High NRF2 expression was associated with low treatment response rate in platinum-based chemotherapy (HR = 0.11, 95% CI 0.02-0.51; P = 0.005). High expression level of NRF2 is predictive for poor overall survival rate (HR = 1.86, 95% CI 1.44-2.41, P < 0.001) and poor progression-free survival (PFS) (HR = 2.27, 95% CI 1.26-4.09, P = 0.006). Compared to patients with a low level of NRF2 expression, patients with high NRF2 expression levels were associated with worse OS and PFS when given the chemotherapy or EGFR-TKI. Together, our meta-analysis results suggest that NRF2 can act as a potential indicator of NSCLC tumour aggressiveness and help the prognosis and design of a better treatment strategy for NSCLC patients.
| S-EPMC7665804 | biostudies-literature
Project description:BackgroundTP53 is an important tumor suppressor gene on human 17th chromosome with its mutations more than 60% in tumor cells. Lung cancer is the highest incidence malignancy in men around the world. N-6 methylase (m6A) is an enzyme that plays an important role in mRNA splicing, translation, and stabilization. However, its role in TP53-mutant non-small-cell lung cancer (NSCLC) remains unknown.MethodFirst, we investigated 17 common m6A regulators' prognostic values in NSCLC. Then, after the establishment of risk signature, we explored the diagnostic value of m6A in TP53-mutant NSCLC. Finally, gene set enrichment analysis (GSEA), gene ontology (GO) enrichment analysis, and differential expression analysis were used to reveal the possible mechanism of m6A regulators affecting TP53-mutant NSCLC patients.ResultsStudy showed that nine m6A regulators (YTHDC2, METTL14, FTO, METTL16, YTHDF1, HNRNPA2B1, RBM15, KIAA1429, and WTAP) were expressed differently between TP53-mutant and wild-type NSCLC (p < 0.05); and ALKBH5 and HNRNPA2B1 were associated with the prognostic of TP53-mutant patients. After construction of the risk signature combined ALKBH5 and HNRNPA2B1, we divided patients with TP53 mutations into high- and low-risk groups, and there was a significant survival difference between two groups. Finally, 338 differentially expression genes (DEGs) were found between high- and low-risk groups. GO enrichment analysis, PPI network, and GSEA enrichment analysis showed that m6A may affect the immune environment in extracellular and change the stability of mRNA.ConclusionIn conclusion, m6A regulators can be used as prognostic predictors in TP53-mutant patients.
| S-EPMC8761469 | biostudies-literature