Prognostic Marker For Non-small Cell Lung Cancer Patients Research Articles

CircPTN Promotes the Progression of Non-Small Cell Lung Cancer through Upregulation of E2F2 by Sponging miR-432-5p.

Background Non-small cell lung cancer (NSCLC) is one of the most prevalent cancers, accounting for around 80% of total lung cancer cases worldwide. Exploring the function and mechanism of circRNAs could provide insights into the diagnosis and treatment for NSCLC. Methods In this study, we collected tumor tissues and adjacent normal tissues from NSCLC patients to detect the expression level of circPTN and analyzed the association of its expression level with the clinicopathological parameter of NSCLC patients. Moreover, the functional engagement of circPTN in NSCLC cells was examined by cell counting kit-8 (CCK-8) cell proliferation assay, transwell migration and invasion assays, and tube formation assay. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting (WB) analysis were used to detect gene and protein expression, respectively. The molecular targets of cicrPTN were predicted using starBase online resources, which was validated by RNA immunoprecipitation (RIP) and dual-luciferase reporter assay. Results Compared with adjacent normal tissues, there was a remarkable increase of the circPTN levels in NSCLC tissues. A high level of circPTN expression was associated with more lymph node metastasis (LNM) and advanced TNM stages. Functionally, circPTN knockdown inhibited the proliferation, migration, and invasion and tube formation ability of NSCLC cells. We further demonstrated that circPTN regulated the malignant phenotype of NSCLC cells through targeting the miR-432-5p/E2F2 axis. Conclusion Together, our results suggest that circPTN, which is upregulated in NSCLC tissues, could serve as a prognostic marker for NSCLC patients. circPTN regulates the malignant progression of NSCLC cells through targeting the miR-432-5p/E2F2 axis, which may be employed as a potential strategy for the management of NSCLC.

Prognostic impact of the pre-treatment controlling nutritional status score in patients with non-small cell lung cancer: A meta-analysis.

Background:The influence of pre-treatment controlling nutritional status (CONUT) score on the prognosis of non-small cell lung cancer (NSCLC) patients is inconclusive. We performed this meta-analysis to evaluate the prognostic significance of CONUT score in NSCLC patients.Methods:A systematic literature review was conducted using PubMed, Embase, and the Cochrane Library databases. The hazard ratio (HR) and 95% confidence interval (CI) were extracted to assess the correlation between the CONUT score and the overall survival (OS), disease-free survival (DFS), recurrence-free survival (RFS), as well as the cancer-specific survival.Results:A total of 11 studies with 3029 patients were included in the analysis. Pooled results indicated that a high CONUT score was positively correlated with poor OS (HR: 1.63, 95%CI: 1.40–1.88, P < .001) and shortened DFS/RFS (HR: 1.65, 95%CI: 1.35–2.01, P < .001), but no significant relationship with the cancer-specific survival (HR: 1.28, 95%CI: 0.60–2.73, P = .517) was identified. The negative effect of high CONUT score on the OS and DFS/RFS was detected in every subgroup with varying treatment methods, cancer stage, CONUT cut-off values, sample size, and analysis methods of HR. Additionally, preoperative high CONUT score was an independent predictor of postoperative complications (odds ratio: 1.58, 95%CI: 1.21–2.06, P = .001) in NSCLC. Last but not least, high CONUT score was not significantly correlated with the patients’ sex, smoking status, cancer stage, lymphatic invasion, vascular invasion, pleural invasion, and pathological cancer type.Conclusion:These results demonstrate that high CONUT score is positively related to poor prognoses. The CONUT score may therefore be considered as an effective prognostic marker in NSCLC patients.

Circulating miR-320a Acts as a Tumor Suppressor and Prognostic Factor in Non-small Cell Lung Cancer.

Dysregulated expression profiles of microRNAs (miRNAs) have been observed in several types of cancer, including non-small cell lung cancer (NSCLC); however, the diagnostic and prognostic potential of circulating miRNAs in NSCLC remains largely undefined. Here we found that circulating miR-320a was significantly down-regulated (~5.87-fold; p < 0.0001) in NSCLC patients (n = 80) compared to matched control plasma samples from healthy subjects (n = 80). Kaplan-Meier survival analysis revealed that NSCLC patients with lower levels of circulating miR-320a had overall poorer prognosis and survival rates compared to patients with higher levels (p < 0.0001). Moreover, the diagnostic and prognostic potential of miR-320a correlated with clinicopathological characteristics such as tumor size, tumor node metastasis (TNM) stage, and lymph node metastasis. Functionally, depletion of miR-320a in human A549 lung adenocarcinoma cells induced their metastatic potential and reduced apoptosis, which was reversed by exogenous re-expression of miR-320a mimics, indicating that miR-320a has a tumor-suppressive role in NSCLC. These results were further supported by high levels of epithelial-mesenchymal transition (EMT) marker proteins (e.g., Beta-catenin, MMP9, and E-cadherin) in lung cancer cells and tissues via immunoblot and immunohistochemistry experiments. Moreover, through bioinformatics and dual-luciferase reporter assays, we demonstrated that AKT3 was a direct target of miR-320a. In addition, AKT3-associated PI3K/AKT/mTOR protein-signaling pathways were elevated with down-regulated miR-320a levels in NSCLC. These composite data indicate that circulating miR-320a may function as a tumor-suppressor miRNA with potential as a prognostic marker for NSCLC patients.

Genetic variants in NPAS2 gene and clinical outcomes of resectable non-small-cell lung cancer.

Background: A series of studies have demonstrated that NPAS2 plays a critical role in the development and progression of several cancers. However, the association between genetic variants in theNPAS2 gene and the clinical outcome of patients with non-small-cell lung cancer (NSCLC) has not been investigated. Methods: Six functional SNPsin NPAS2were selected and genotyped using the Sequenom iPLEX genotyping system in a cohort of 484 Chinese NSCLC patients undergoing surgery. Multivariate Cox proportional hazards model were used for the prognosis analysis. Results: We found that SNP rs2305158 exhibited a significant association with overall survival of NSCLC patients in the dominant model (hazard ratio [HR]: 0.68; 95% CI: 0.49-0.95; p=0.02). Lymph node metastasis was significantly associated with increased death risk (HR: 1.73; 95% CI: 1.24-2.40; p=0.001) in patients with the homozygous wildtype (WW) genotype of rs2305158. However, no significant association was observed between them in patients carrying a heterozygous variant (WV) or homozygous variant (VV) genotype of rs2305158. Finally, in the joint and interaction analysis, the patients carrying homozygous wildtype (WW) genotype and lymph node metastasis from N1 to N3 conferred a significant increased effect on death (HR: 2.29; 95% CI: 1.40-3.76; p=0.001). Conclusions: Our results suggest that NPAS2polymorphisms may serve as an independent prognostic marker for NSCLC patients.

Prognostic and Predictive Significance of PD-L1 Expression in Non-Small Cell Lung Cancer Patients: A Single-Center Experience.

To investigate the prognostic and predictive value of PD-L1 expression in operated non-small cell lung cancer (NSCLC) patients and to analyze its relationship with clinicopathological factors. A total of 90 patients with operable NSCLC were included in this retrospective single center study. Tumor blocks of patients were stained immunohistochemically with PD-L1 polyclonal antibody. When evaluated immunohistochemically and statistically, patients with tumor staining percentage of ≥5%, those with +2 and +3 membranous staining intensity, and those with ≥50% H-Score were considered positive. The relationship between PD-L1 expression status and clinicopathological features in addition to the prognostic effect of PD-L1 on survival were statistically analyzed. The frequency of PD-L1 expression was 37%, 15% and 5% according to the staining percentage, staining intensity, and the H-Score, respectively. There was no significant relationship between PD-L1 expression and age, gender, smoking, tumor stage and histological subtype (p > 0.05). However, PD-L1 expression was relatively higher in patients < 65 years of age, men, smokers, patients with advanced tumor stage, and squamous cell subtype. Based on the analysis of the H-Score, no significant difference was noted regarding disease-free survival time between PD-L1 positive and PD-L1 negative patients (median 20 [95% CI 1.2-38.7] months vs. median 27 [95% CI 17.5-36] months, p=0.208). However, overall survival time was significantly shorter in PD-L1 positive compared to PD-L1 negative patients (median 24 months [95% CI 9.9-38] vs. median 48 months [95% CI 33.6-62.3], p=0.049). In patients with high PD-L1 expression, the biological behavior of the cancer was more aggressive, and the life expectancy was shorter. PD-L1 expression seems to be a poor prognostic marker in NSCLC patients.

Cul4A Modulates Invasion and Metastasis of Lung Cancer Through Regulation of ANXA10.

Cullin 4A (Cul4A) is overexpressed in a number of cancers and has been established as an oncogene. This study aimed to elucidate the role of Cul4A in lung cancer invasion and metastasis. We observed that Cul4A was overexpressed in non-small cell lung cancer (NSCLC) tissues and the overexpression of Cul4A was associated with poor prognosis after surgical resection and it also decreased the expression of the tumor suppressor protein annexin A10 (ANXA10). The knockdown of Cul4A was associated with the upregulation of ANXA10, and the forced expression of Cul4A was associated with the downregulation of ANXA10 in lung cancer cells. Further studies showed that the knockdown of Cul4A inhibited the invasion and metastasis of lung cancer cells, which was reversed by the further knockdown of ANXA10. In addition, the knockdown of Cul4A inhibited lung tumor metastasis in mouse tail vein injection xenograft models. Notably, Cul4A regulated the degradation of ANXA10 through its interaction with ANXA10 and ubiquitination in lung cancer cells. Our findings suggest that Cul4A is a prognostic marker in NSCLC patients, and Cul4A plays important roles in lung cancer invasion and metastasis through the regulation of the ANXA10 tumor suppressor.

CHST11 Promotes Lung Cancer Metastasis through Changing Intracellular Iron Metabolism

Non‐small‐cell lung cancer (NSCLC) is one of the most lethal cancers, for it often develops metastasis after therapy. Cancer metastasis usually begins from epithelial‐to‐mesenchymal transition (EMT), and metabolic disorder is a key mediator of lung cancer EMT. The linkage between metabolic disorder and NSCLC EMT is still unclear. Here, we compared gene expression signatures from both TGFb induction EMT model of NSCLC cells and the EMT score from clinical NSCLC patients' cohort. We found several chondroitin sulfate (CS) biosynthesis genes were highly correlated to NSCLC EMT status. CHST11, the key enzyme of this pathway, was selected for further functional studies. Enforced CHST11 expression promoted NSCLC cells migration, invasion and increasing M‐type markers, such as Slug, N‐cadherin and Vimentin expression and vise versa. Deplete the final product of CS biosynthesis by chondroitinase ABC or enzyme‐dead CHST11 could abolish the NSCLC EMT ability from TGFb and CHST11, respectively. Moreover, we found the CHST11 expression changing the iron metabolic status in NSCLC cells and promoting the NSCLC EMT.In the end, immunohistochemistry showed that CHST11 was a poor prognostic marker of overall survival and disease‐free survival in clinical NSCLC patients. In conclusion, our findings implicated that 1) The chondroitin sulfate biosynthesis pathways is crucial for NSCLC EMT; 2) A novel CHST11‐CP‐Fe3+ pathway is involved in NSCLC EMT. 3) CHST11 is a poor prognostic marker in NSCLC patients. These results might help us to understand the role of aberrant cancer metabolism in NSCLC EMT.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

A Meta Analysis on Prognostic Value of Patients with Non-Small Cell Lung Cancer

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 using Review Manager version 5.3. The results of analysis were presented as hazard ratio (HR) or odds ratios with 95% confidence interval (95% CI). Subgroup analysis based on ethnicity of NSCLC patients was conducted to illustrate the potential discrepancy. Significant heterogeneity was considered at I2 &gt; 50% and P &lt; 0.05, and random-effects model was used. The combined results indicated that higher NF-κB expression was associated with shorter overall survival 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 &lt; 0.0001) and lymph node metastasis (HR = 0.56, 95% CI = 0.38–0.83, P = 0.004). We conclude that NF-κB expression may be a potential unfavorable prognostic marker for NSCLC patients.

Diagnostic and prognostic value of serum Cripto‐1 in patients with non‐small cell lung cancer

Cripto-1 (CR-1) is a member of the epidermal growth factor (EGF)-CFC protein family, which is involved in tumor pathogenesis. This study aimed to explore the diagnostic and prognostic value of serum CR-1 level in patients with non-small cell lung cancer (NSCLC). Serum specimens from 312 NSCLC patients and 120 healthy controls were collected. Serum CR-1 level was measured using enzyme-linked immunosorbent assay. The serum CR-1 level was significantly elevated in NSCLC patients compared with healthy controls (P<.001). Higher serum CR-1 level was associated with advanced TNM stage, lymph node metastasis and distant metastasis. With a cutoff value of 1.67ng/mL, CR-1 showed a good diagnostic performance for NSCLC. Kaplan-Meier log rank analysis revealed that the low serum CR-1 patients had a better overall survival (OS) and progression-free survival (PFS) compared with high CR-1 patients (P=.004 and .001, respectively). Further univariate and multivariate Cox regression analyses showed that serum CR-1 level was an independent risk factor of prognosis of NSCLC patients. Our study suggests that serum CR-1 level is a useful diagnostic and prognostic marker for NSCLC patients.

Progression and prognostic value of ECT2 in non-small-cell lung cancer and its correlation with PCNA.

PurposeEpithelial cell transforming sequence 2 (ECT2) is a guanine nucleotide exchange factor, which is involved in cell division regulation and cell cycle modulation. Recent evidence indicates that ECT2 is overexpressed in many human cancers. However, the exact prognostic value of ECT2 in lung cancer has not been elucidated.Patients and methodsIn the current study, we performed correlation and prognosis analyses using public databases and conducted immunohistochemical staining in tissue microarrays, using samples from 204 lung cancer patients with survival data.ResultsWe found that the expression of ECT2 was markedly increased in lung cancer tissues compared with normal tissues. Moreover, we demonstrated that the expression of ECT2 was related to tumor cell differentiation degree, TNM stage, lymph node metastasis, and prognosis in non-small-cell lung cancer (NSCLC). A correlation analysis indicated that ECT2 levels were significantly correlated with proliferating cell nuclear antigen (PCNA) levels in NSCLC. Furthermore, Kaplan–Meier analyses revealed that high ECT2 expression was associated with unfavorable overall survival (OS) and progression-free survival (PFS) in NSCLC patients.ConclusionTaken together, these results indicate that the overexpression of ECT2 contributes to tumor invasion and progression, suggesting that ECT2 is a potential prognostic marker for NSCLC patients.

Prognostic significance of NF-κB expression in non-small cell lung cancer: A meta-analysis.

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.

Cell cycle‐related and expression‐elevated protein in tumor overexpression is associated with proliferation behaviors and poor prognosis in non‐small‐cell lung cancer

The cell cycle‐related and expression‐elevated protein in tumor (CREPT) is overexpressed in several human malignancies. However, the clinical relevance of CREPT expression and its biological role in non‐small‐cell lung cancer (NSCLC) remains unclear. In this study, we detected the expression of CREPT in both NSCLC tissues and cell lines by immunohistochemistry, Western blot analysis, and RT‐PCR. The correlation between CREPT expression and clinicopathologic features was analyzed in 271 NSCLC patients. The prognostic value of CREPT expression was evaluated by Kaplan–Meier analysis and Cox regression analysis. CREPT was overexpressed in Calu‐1 cell lines by using plasmid vector and its biological function was explored both in vitro and in vivo. We found that CREPT was significantly overexpressed in NSCLC compared with paired adjacent non‐tumor tissues, and the expression level of CREPT was correlated with tumor differentiation, lymph node metastasis, and clinical stage. Kaplan–Meier analysis showed that the recurrence‐free survival and overall survival of high CREPT expression groups were significantly shorter than those of the low CREPT expression group. Multivariate analysis identified that CREPT might be an independent biomarker for the prediction of NSCLC prognosis. Overexpression of CREPT increased cell proliferation and enhanced the migration and invasion ability of Calu‐1 cells (a human NSCLC cell line with relative low CRPET expression) in vitro. Moreover, CREPT overexpression promoted tumor growth in a nude mice model. These results suggest that CREPT is closely relevant to the proliferation of NSCLC cells and it might be a potential prognostic marker in NSCLC patients.

Ubiquitin conjugating enzyme E2 L3 promoted tumor growth of NSCLC through accelerating p27kip1 ubiquitination and degradation.

The molecular pathogenesis of human lung cancer has not been completely clarified. Here, we reported that UBE2L3, a member of the ubiquitin-conjugating enzymes (E2s), were overexpressed in non-small-cell lung cancer (NSCLC) tissues compared with the non-tumor tissues. High expression of UBE2L3 was correlated with advanced tumor stage and adverse outcomes. Knockdown of UBE2L3 inhibited NSCLC cell growth while ectopic expression of UBE2L3 promoted NSCLC cell growth in a cell cycle dependent manner. The results of subcutaneous tumor xenograft studies revealed that knockdown of UBE2L3 attenuated the in vivo tumor growth. Mechanistically, we observed that UBE2L3 could interact with F-box protein Skp2, a member of the SCF (Skp2) ubiquitin ligase complex, and thus promoted the ubiquitination and proteasomal degradation of p27kip1. Furthermore, NSCLC cases with high level of UBE2L3 and low level of p27kip1 had worst prognosis, suggesting that combination of UBE2L3 and p27kip1 is a more powerful prognostic marker for NSCLC patients. Taken together, the current study presented a novel marker for predicting prognosis and a potential therapeutic target for NSCLC patients.

Hyperphosphorylation of RPS6KB1, rather than overexpression, predicts worse prognosis in non-small cell lung cancer patients.

RPS6KB1 is the kinase of ribosomal protein S6 which is 70 kDa and is required for protein translation. Although the abnormal activation of RPS6KB1 has been found in types of diseases, its role and clinical significance in non-small cell lung cancer (NSCLC) has not been fully investigated. In this study, we identified that RPS6KB1 was over-phosphorylated (p-RPS6KB1) in NSCLC and it was an independent unfavorable prognostic marker for NSCLC patients. In spite of the frequent expression of total RPS6KB1 and p-RPS6KB1 in NSCLC specimens by immunohistochemical staining (IHC), only p-RPS6KB1 was associated with the clinicopathologic characteristics of NSCLC subjects. Kaplan-Meier survival analysis revealed that the increased expression of p-RPS6KB1 indicated a poorer 5-year overall survival (OS) for NSCLC patients, while the difference between the positive or negative RPS6KB1 group was not significant. Univariate and multivariate Cox regression analysis was then used to confirm the independent prognostic value of p-RPS6KB1. To illustrate the underlying mechanism of RPS6KB1 phosphorylation in NSCLC, LY2584702 was employed to inhibit the RPS6KB1 phosphorylation specifically both in lung adenocarcinoma cell line A549 and squamous cell carcinoma cell line SK-MES-1. As expected, RPS6KB1 dephosphorylation remarkably suppressed cells proliferation in CCK-8 test, and promoted more cells arresting in G0-G1 phase by cell cycle analysis. Moreover, apoptotic A549 cells with RPS6KB1 dephosphorylation increased dramatically, with an elevating trend in SK-MES-1, indicating a potential involvement of RPS6KB1 phosphorylation in inducing apoptosis. In conclusion, our data suggest that RPS6KB1 is over-activated as p-RPS6KB1 in NSCLC, rather than just the total protein overexpressing. The phosphorylation level of RPS6KB1 might be used as a novel prognostic marker for NSCLC patients.

Diagnostic and prognostic values of endothelial-cell-specific molecule-1 with malignant pleural effusions in patients with non-small cell lung cancer.

Over-expressed endothelial-cell-specific molecule-1 (ESM-1) in tumor vascular endothelium contributes to tumor angiogenesis, metastasis, and poor prognosis. However, the content of ESM-1 in pleural effusion is unclear. A retrospective study was carried out to investigate the diagnostic and prognostic values of ESM-1 with malignant pleural effusions in patients with non-small cell lung cancer (NSCLC). ESM-1 levels in malignant pleural effusion (MPE) from 70 patients with NSCLC and 50 cases of benign pleural effusion (BPE) were measured using enzyme-linked immunosorbent assay. Receiver operating characteristic (ROC) curve was calculated to assess the diagnostic value of ESM-1. Survival curves were performed by Kaplan-Meier method and survival characteristics were compared by log-rank test. Univariable and multivariate Cox proportional hazards model were carried out to analysis the significance of different prognostic factors for overall survival (OS). ESM-1 levels were significantly higher in MPE than those in BPE (p < 0.001). By ROC curve analysis, with a cutoff level of 19.58 ng/ml, the accuracy, sensitivity, and specificity for ESM-1 diagnosis MPE were 82.5%, 81.4%, and 84.0%, respectively. Moreover, NSCLC patients with pleural fluid ESM-1 levels below 19.58 ng/ml had significant longer OS than those patients with higher levels (22.09 months vs. 11.49 months, p = 0.003). Multivariate survival analysis showed that high MPE ESM-1 level was an independent prognostic factor (HR, 1.007; p = 0.039) for the OS of NSCLC patients. This study showed that ESM-1 level in pleural effusion could be a potential diagnostic and prognostic marker in NSCLC patients with MPE.

RETRACTED: The Pseudogene DUXAP8 Promotes Non-small-cell Lung Cancer Cell Proliferation and Invasion by Epigenetically Silencing EGR1 and RHOB

Recently, the non-protein-coding functional elements in the human genome have been identified as key regulators in postgenomic biology, and a large number of pseudogenes as well aslong non-coding RNAs (lncRNAs) have been found to be transcribed in multiple human cancers. However, only a small proportion of these pseudogenes has been functionally characterized. In this study, we screened for pseudogenes associated with human non-small-cell lung cancer (NSCLC) by comparative analysis of several independent datasets from the GEO. We identified a transcribed pseudogene named DUXAP8 that is upregulated in tumor tissues. Patients with higher DUXAP8 expression exhibited shorter survival, suggesting DUXAP8 as a new candidate prognostic marker for NSCLC patients. Knockdown of DUXAP8 impairs cell growth, migration, and invasion, and induces apoptosis both invitro and invivo. Mechanistically, DUXAP8 represses the tumor suppressors EGR1 and RHOB by recruiting histone demethylase LSD1 and histone methyltransferase EZH2, thereby promoting cell proliferation, migration, and invasion. These findings indicate that the pseudogene DUXAP8 may act as an oncogene in NSCLC by silencing EGR1 and RHOB transcription by binding with EZH2 and LSD1, which may offer a novel therapeutic target for this disease.

Overexpression of KIAA1199: An independent prognostic marker in nonsmall cell lung cancer.

KIAA1199 has been identified as an oncogene in many cancers. Here, we collected 153 cases of nonsmall cell lung cancer (NSCLC) tissues to investigate the relationships between KIAA1199 protein and clinical factors. Immunohistochemistry (IHC) staining was used to detect the expression of KIAA1199. Follow-up included blood analysis, chest X-ray, ultrasound examination, and computed tomography was carried out every 3 months for the first 2 years and at 6-month intervals thereafter during the follow-up period (3 years). Kaplan-Meier survival analysis and Cox analysis were applied to identify the relationship between KIAA1199 and NSCLC. IHC results showed that 76 (49.67%) specimens had strong expression of KIAA1199 protein, with poor differentiation (P = 0.003), higher positive lymph node metastasis (P = 0.037), and higher tumor node metastasis stage (P = 0.016). Using Kaplan-Meier survival analysis, it is found that patients with high KIAA1199 protein expression have poor overall survival (P = 0.004). Cox analysis suggested that the KIAA1199 protein was an independent prognostic marker for NSCLC patients (P = 0.040). Our findings revealed that KIAA1199 protein could be applied in predicting NSCLC patient's outcome.

Diagnostic and prognostic value of serum periostin in patients with non-small cell lung cancer.

The periostin protein is expressed in a variety of human malignancies. The aim of this study was to explore the diagnostic and prognostic value of serum periostin levels in patients with non-small cell lung cancer (NSCLC). We measured serum periostin levels by ELISA in 296 NSCLC patients, 120 benign lung diseases (BLD) patients and 160 healthy controls. The levels of serum periostin in NSCLC patients were significantly elevated compared with those in healthy controls (P < 0.001) and BLD patients (P < 0.001). Using a cutoff value of 30.87 ng/ml, the sensitivity and specificity of periostin in differentiating between NSCLC patients and BLD patients, and between NSCLC patients and healthy controls was, 48.6 and 91.7%, and 51.4 and 97.5%, respectively. Kaplan-Meier log rank analysis revealed that the higher serum periostin levels group had a poorer progression-free survival (PFS) and overall survival (OS) compared with lower periostin group (P = 0.024, P = 0.015, respectively). Further univariate and multivariate Cox regression analysis showed that serum periostin was an independent risk factor of prognosis of NSCLC patients. In conclusion, our study suggests that serum periostin could be considered as a diagnostic and prognostic marker for NSCLC patients.

Gene Expression of the EGF System—a Prognostic Model in Non–Small Cell Lung Cancer Patients Without Activating EGFR Mutations

OBJECTIVES: Contradicting results have been demonstrated for the expression of the epidermal growth factor receptor (EGFR) as a prognostic marker in non–small cell lung cancer (NSCLC). The complexity of the EGF system with four interacting receptors and more than a dozen activating ligands is a likely explanation. The aim of this study is to demonstrate that the combined network of receptors and ligands from the EGF system is a prognostic marker. MATERIAL AND METHODS: Gene expression of the receptors EGFR, HER2, HER3, HER4, and the ligands AREG, HB-EGF, EPI, TGF-α, and EGF was measured by quantitative polymerase chain reaction in tumor samples from 100 NSCLC patients without EGFR activating mutations. Results were dichotomized into high or low levels of target expression. Coexpression of the ligands and receptors was observed, and a score was developed based on the summed effect of receptors and ligands. Akaike’s information criteria selected the optimal score. Results were correlated with age, sex, stage, histology, performance status, and overall survival. RESULTS: Patients were randomly split 1:1 to create test and validation cohorts. In multivariate analyses, the only individual prognostic marker was EPI (hazard ratio [HR] 0.38 [0.20-0.72], P = .003). The optimal score in the test cohort was validated as a marker of inferior survival in the validation cohort and by bootstrapping. Multivariate analysis confirmed the combined score as a prognostic marker of inferior survival (HR 3.75 [2.17-6.47], P < .00001). CONCLUSION: Our study has developed a model that takes the complexity of the EGF system into account and shows that this model is a strong prognostic marker in NSCLC patients.

Nutritional status in the era of target therapy: poor nutrition is a prognostic factor in non-small cell lung cancer with activating epidermal growth factor receptor mutations.

Background/AimsPretreatment nutritional status is an important prognostic factor in patients treated with conventional cytotoxic chemotherapy. In the era of target therapies, its value is overlooked and has not been investigated. The aim of our study is to evaluate the value of nutritional status in targeted therapy.MethodsA total of 2012 patients with non-small cell lung cancer (NSCLC) were reviewed and 630 patients with activating epidermal growth factor receptor (EGFR) mutation treated with EGFR tyrosine kinase inhibitor (TKI) were enrolled for the final analysis. Anemia, body mass index (BMI), and prognostic nutritional index (PNI) were considered as nutritional factors. Hazard ratio (HR), progression-free survival (PFS) and overall survival (OS) for each group were calculated by Cox proportional analysis. In addition, scores were applied for each category and the sum of scores was used for survival analysis.ResultsIn univariable analysis, anemia (HR, 1.29; p = 0.015), BMI lower than 18.5 (HR, 1.98; p = 0.002), and PNI lower than 45 (HR, 1.57; p < 0.001) were poor prognostic factors for PFS. Among them, BMI and PNI were independent in multi-variable analysis. All of these were also significant prognostic values for OS. The higher the sum of scores, the poorer PFS and OS were observed.ConclusionsPretreatment nutritional status is a prognostic marker in NSCLC patients treated with EGFR TKI. Hence, baseline nutritional status should be more carefully evaluated and adequate nutrition should be supplied to these patients.