Overall Survival In Lung Cancer Research Articles

Radiomics-Based Prediction of Overall Survival in Lung Cancer Using Different Volumes-Of-Interest

Lung cancer accounts for the largest amount of deaths worldwide with respect to the other oncological pathologies. To guarantee the most effective cure to patients for such aggressive tumours, radiomics is increasing as a novel and promising research field that aims at extracting knowledge from data in terms of quantitative measures that are computed from diagnostic images, with prognostic and predictive ends. This knowledge could be used to optimize current treatments and to maximize their efficacy. To this end, we hereby study the use of such quantitative biomarkers computed from CT images of patients affected by Non-Small Cell Lung Cancer to predict Overall Survival. The main contributions of this work are two: first, we consider different volumes of interest for the same patient to find out whether the volume surrounding the visible lesions can provide useful information; second, we introduce 3D Local Binary Patterns, which are texture measures scarcely explored in radiomics. As further validation, we show that the proposed signature outperforms not only the features automatically computed by a deep learning-based approach, but also another signature at the state-of-the-art using other handcrafted features.

Identification of Hub Genes as Biomarkers Correlated with the Proliferation and Prognosis in Lung Cancer: A Weighted Gene Co-Expression Network Analysis.

Lung cancer is one of the most malignant tumors in the world. Early diagnosis and treatment of lung cancer are vitally important to reduce the mortality of lung cancer patients. In the present study, we attempt to identify the candidate biomarkers for lung cancer by weighted gene co-expression network analysis (WGCNA). Gene expression profile of GSE30219 was downloaded from the gene expression omnibus (GEO) database. The differentially expressed genes (DEGs) were analyzed by the limma package, and the co-expression modules of genes were built by WGCNA. UALCAN was used to analyze the relative expression of normal group and tumor subgroups based on tumor individual cancer stages. Survival analysis for the hub genes was performed by Kaplan–Meier plotter analysis with the TCGA database. A total of 2176 genes (745 upregulated and 1431 downregulated genes) were obtained from the GSE30219 database. Seven gene co-expression modules were conducted by WGCNA and the blue module might be inferred as the most crucial module in the pathogenesis of lung cancer. In the pathway enrichment analysis of KEGG, the candidate genes were enriched in the “DNA replication,” “Cell cycle,” and “P53 signaling pathway” pathways. Among these, the cell cycle pathway was the most significant pathway in the blue module with four hub genes CCNB1, CCNE2, MCM7, and PCNA which were selected in our study. Kaplan–Meier plotter analysis indicated that the high expressions of four hub genes were correlated with a worse overall survival (OS) and advanced tumors. qRT-PCR showed that mRNA expression levels of MCM7 (p = 0.038) and CCNE2 (0.003) were significantly higher in patients with the TNM stage. In summary, the high expression of the MCM7 and CCNE2 were significantly related with advanced tumors and worse OS in lung cancer. Thus, the MCM7 and CCNE2 genes can be good indicators for cellular proliferation and prognosis in lung cancer.

Comprehensive analysis of the expression and prognosis for TFAP2 in human lung carcinoma.

The TFAP2 family of transcription factors, regulating gene expression related to vertebrate evolution, have been studied extensively in human cancer. However, the distinct roles of each TFAP2 in the expression and prognostic significance of lung carcinoma have not been elucidated yet. This study is aimed to identify the mRNA expression and prognostic value of TFAP2 family in human lung cancer. The transcriptional and survival data of TFAP2s in patients with lung cancer were obtained via ONCOMINE, LinkedOmics, GEPIA, cBioPortal, Kaplan-Meier Plotter and Human Protein Atlas databases. The results showed that expression levels of TFAP2A and TFAP2C were higher in lung adenocarcinoma and squamous cell carcinoma tissues than in normal lung tissues, whereas no difference was found in the TFAP2B expression level. TFAP2A was related to an unfavorable overall survival in lung cancer and its upregulation was significantly related to the overall survival in patients with smoking, non-chemotherapy and non-radiotherapy. This study implied that TFAP2A was a reliable prognostic factor, which could be a potential marker for improving survival and prognostic accuracy of lung cancer patients.

RNA Sequencing Analyses Reveal the Potential Mechanism of Pulmonary Injury Induced by Gallium Arsenide Particles in Human Bronchial Epithelioid Cells

Extensive use of gallium arsenide (GaAs) has led to increased exposure to humans working in the semiconductor industry. This study employed physicochemical characterization of GaAs obtained from a workplace, cytotoxicity analysis of damage induced by GaAs in 16HBE cells, RNA-seq and related bioinformatic analysis, qRT-PCR verification and survival analysis to comprehensively understand the potential mechanism leading to lung toxicity induced by GaAs. We found that GaAs-induced abnormal gene expression was mainly related to the cellular response to chemical stimuli, the regulation of signalling, cell differentiation and the cell cycle, which are involved in transcriptional misregulation in cancer, the MAPK signalling pathway, the TGF-β signalling pathway and pulmonary disease-related pathways. Ten upregulated genes (FOS, JUN, HSP90AA1, CDKN1A, ESR1, MYC, RAC1, CTNNB1, MAPK8 and FOXO1) and 7 downregulated genes (TP53, AKT1, NFKB1, SMAD3, CDK1, E2F1 and PLK1) related to GaAs-induced pulmonary toxicity were identified. High expression of HSP90AA1, RAC1 and CDKN1A was significantly associated with a lower rate of overall survival in lung cancers. The results of this study indicate that GaAs-associated toxicities affected the misregulation of oncogenes and tumour suppressing genes, activation of the TGF-β/MAPK pathway, and regulation of cell differentiation and the cell cycle. These results help to elucidate the molecular mechanism underlying GaAs-induced pulmonary injury.

Safety and outcomes of immunotherapy re-challenge in lung cancer.

e19355 Background: Immune checkpoint inhibitors (CIs) have been shown to improve overall survival in lung cancer and are FDA approved in multiple settings, both as single agents and in combination with chemotherapy. Immune related adverse events (irAEs) are common and frequently manifest as dermatitis, pneumonitis, colitis, and hepatitis, among others. Managing grade 2 or higher irAEs often requires multiple outpatient visits and sometimes inpatient admissions, which can significantly increase patient morbidity and healthcare cost. There is limited evidence on the safety of restarting CIs after moderate to severe irAE. Identifying high-risk factors for developing severe irAEs again after re-challenge can improve patient care and cost efficiency. Methods: We searched our electronic medical records to identify patients with NSCLC and SCLC treated with one or more PD-1, PD-L1, or CTLA-4 CIs at our institution between 2013 and 2019. We reviewed 452 patients and identified 44 patients who developed irAE requiring treatment discontinuation. Of these 44 patients, 19 were re-challenged with same or different CIs. The primary end point of this study is to assess the rate of grade 2 or higher irAE after CI re-challenge. Secondary endpoints are mortality rate, overall survival, and disease status. Results: Median follow up for the 19 patients who were re-challenged with CI was 15 months. Median duration of CI treatment after re-challenge was 6 months (range 0.5 to 25 months). 7 patients (37%) developed irAEs (grade 2 or above) again (5 pts with same irAE as prior). Multivariate logistic regression analysis revealed that age≥70 and requirement of steroid for initial irAEs were associated with a higher risk of recurrent irAEs. Median overall survival has not yet been reached; 32% of patients have died. No deaths were related to irAE. After re-challenge with CIs, 42% of the patients had partial response or stable disease, and 58% had progression of disease. Conclusions: Our study demonstrated that re-challenge with immunotherapy is feasible in some patients who had treatment held due to irAEs, though recurrent irAEs were common. Caution should be taken when restarting CIs after moderate to severe toxicities, especially in older adults.

Identification of Potential Diagnostic and Prognostic Values of P4HA1 Expression in Lung Cancer, Breast Cancer, and Head and Neck Cancer.

The aims of this study were to investigate the expression of prolyl 4-hydroxylase subunit alpha-1 (P4HA1) and its relationship with clinicopathological features in lung cancer (LC), breast cancer (BC), and head and neck cancer (HNSC) and to discuss the possibility of P4HA1 being a potential diagnostic and prognostic biomarker. Data on the RNA expression profile, protein expression profile, and relevant clinical information were downloaded from The Cancer Genome Atlas (TCGA) and The Human Protein Atlas databases. The relationship between P4HA1 mRNA expression and clinicopathological features was evaluated. Survival analysis was performed to assess overall survival (OS) and relapse-free survival (RFS). The multivariate Cox regression model was employed to analyze the independent prognostic factors. Finally, protein-protein interaction networks were constructed and enrichment analysis was performed to identify the latent P4HA1-related terms and pathways. This study showed that P4HA1 was upregulated in three types of tumor tissues (p < 0.05) and high P4HA1 was significantly relevant to the clinical features of patients with LC, BC, or HNSC. Survival analysis indicated that patients with high P4HA1 had unfavorable clinical outcomes. Multivariate analysis showed that the high P4HA1 expression was an independent prognostic factor for poor OS and RFS in LC and HNSC patients. Bioinformatic analysis was performed to predict P4HA1-interacted proteins and further evaluate possible signal pathways. In the current study, the rising P4HA1 was identified in LC, BC, and HNSC and significantly correlated with the clinicopathological features of patients. High P4HA1, suggesting poor clinical outcomes, could be used as an early diagnostic and prognostic biomarker for patients with aforementioned tumors.

1758PD - Complementary medicine (CM) use in phase III clinical trials (P3T) conducted by the Canadian Cancer Trials Group (CCTG)

BackgroundCMs are products used concurrently with conventional medicine, including natural products and homeopathy. CM use is prevalent amongst cancer patients, but the use in patients enrolled on P3T had yet to be studied. This study examined patient characteristics and outcomes of CM users enrolled in P3T conducted by the CCTG. MethodsData were acquired from six international P3T and included patients with metastatic breast (BR), colorectal (CRC), and non-small-cell lung cancers (LC) (MA.31, CO.17, 20 &23, BR.21 &26). Medications were independently reviewed by two authors to identify CM; discrepancies reviewed by a third author, and the final list was approved by consensus. Patient characteristics associated with CM use were identified with Chi-square and logistic regression. Propensity score stratification was conducted to compare between CM users and non-users for overall survival (OS), grade 3+ adverse events (AE) and quality of life (QOL) scales (EORTC-QLQ-C30). Results3446 patients were included (17.7% BR, 44.4% CRC, 37.8% LC). Of 24908 medications, 651 (2.6%) were considered CM and 20.4% of patients were CM users. CM use in LC was associated (p<0.05) with ECOG performance status (PS) 0-1 (vs 2+), weight loss <5%, non-smoker, and Eastern Asian ethnicity. CM use in CRC was associated with age ≤65, PS 0-1 (vs 2+), fewer sites of metastases, and normal hemoglobin. CM use in BR was only associated with age <50. CM use did not affect time to global deterioration of QoL (hazard ratio (HR) 1.07 (p=0.22, 95%CI 0.94-1.21)). CM use HRs for OS in LC, CRC, and BC P3T were 0.80 [p=0.005; 95% CI (0.68-0.94)], 0.87 (p=0.08; 95% CI (0.75-1.02)), and 0.85 (p=0.35; 95%CI (0.61-1.19)), respectively. ConclusionsThe use of CM amongst patients enrolled in P3T is high. Patient’s using CM tend to be younger and have better PS. Worse QOL indices were associated with CM use, although time to deterioration and incidence of AE were not. HR for OS in the lung cancer trials favoured CM users, however, this should be interpreted with caution given the retrospective/post-hoc nature of this study and the more favourable baseline characteristics. Clinical trial identificationMA.31- NCT00667251 CO.17- NCT00079066 CO.20- NCT00640471 CO.23- NCT01830621 BR.21- NCT00036647 BR.26- NCT01000025. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureP.A. Bradbury: Honoraria (self), Advisory / Consultancy: AbbVie; Advisory / Consultancy: BI; Advisory / Consultancy: Merck; Honoraria (self): Lilly. C. Karapetis: Advisory / Consultancy: Merck Serono. L.K. Seymour: Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): OSI Pharmaceuticals. All other authors have declared no conflicts of interest.

Race/ethnicity and lung cancer survival in the United States: a meta-analysis.

Lung cancer mortality has been shown to vary by race and ethnicity in cancer registries; however, studies often do not account for smoking status. We sought to summarize the independent contribution of race and ethnicity to survival in US lung cancer patients, accounting for important variables including smoking status. PubMed was used to identify 1,877 potentially eligible studies of which 27 were included. Studies were excluded if they did not account for age, race and/or ethnicity, and smoking status. Fixed- and random-effects meta-analyses were conducted using the reported adjusted hazard ratios (HR) of Hispanic ethnicity and Asian and African-American race compared to Non-Hispanic whites (NHWs) on overall survival in lung cancer. Hispanic ethnicity and Asian race were associated with decreased adjusted risk of death (Hispanic: Nstudies = 5, Nsubjects = 108,810, HR = 0.95, 95% CI 0.90-1.00; Asian: Nstudies = 6, Nsubjects = 128,950, HR = 0.86, 95% CI 0.81-0.90). The results were similar when excluding studies of solely never-smokers. There was no significant difference in survival between African-American and white race after adjustment (Nstudies = 10, Nsubjects = 131,378, HR = 0.98, 95% CI 0.96-1.01). Other prognostic factors were female gender (HR = 0.88, 95% CI 0.87-0.89), unmarried status (HR = 1.08, 95% CI 1.04-1.11), ever-smoking status (HR = 1.11, 95% CI 1.08-1.15), having comorbidities (HR = 1.39, 95% CI 1.24-1.56), and treatment receipt (surgery: HR = 0.33, 95% CI 0.32-0.34; radiation: HR = 0.87, 95% CI 0.85-0.88; chemotherapy: HR = 0.64, 95% CI 0.63-0.65). Even after adjustment for clinical factors and smoking status, Hispanics and Asians experienced improved survival compared to NHWs. Future studies are needed to elucidate the drivers of these survival disparities.

High Aldehyde Dehydrogenase Levels Are Detectable in the Serum of Patients with Lung Cancer and May Be Exploited as Screening Biomarkers.

Objectives Since early detection improves overall survival in lung cancer, identification of screening biomarkers for patients at risk represents an area of intense investigation. Tumor liberated protein (TLP) has been previously described as a tumor-associated antigen (complex) present in the sera from lung cancer patients. Here, we set out to identify the nature of TLP to develop this as a potential biomarker for lung cancer screening. Materials and Methods Beginning from the peptide epitope RTNKEASI previously identified from the TLP complex, we produced a rabbit anti-RTNKEASI serum and evaluated it in the lung cancer cell line A549 by means of immunoblot and peptide completion assay (PCA). The TLP sequence identification was conducted by mass spectrometry. The detected protein was, then, analyzed in patients with non-small cell lung cancer (NSCLC) and benign lung pathologies and healthy donors, by ELISA. Results The anti-RTNKEASI antiserum detected and immunoprecipitated a 55 kDa protein band in the lysate of A549 cells identified as aldehyde dehydrogenase isoform 1A1, revealing the molecular nature of at least one component of the previously described TLP complex. Next, we screened blood samples from a non-tumor cohort of 26 patients and 45 NSCLC patients with different disease stages for the presence of ALDH1A1 and global ALDH. This analysis indicated that serum positivity was highly restricted to patients with NSCLC (ALDH p < 0.001; ALDH1A1 p=0.028). Interestingly, the global ALDH test resulted positive in more NSCLC samples compared to the ALDH1A1 test, suggesting that other ALDH isoforms might add to the sensitivity of the assay. Conclusion Our data indicate that ALDH levels are elevated in the sera of NSCLC patients, even with early stage disease, and may thus be evaluated as part of a marker panel for non-invasive detection of NSCLC.

Influence of the selenium level on overall survival in lung cancer

BackgroundAlthough the results of studies in populations with low selenium status indicate an inverse correlation between body selenium levels and the risk of the lung cancer, the effect of this microelement on survival has not been studied. Materials and MethodsWe performed a prospective study of 302 patients diagnosed with lung cancer in Szczecin, Poland. Selenium concentration in serum was measured at the time of diagnosis and before treatment. All patients were followed for a maximum of 80 months or until death. Vital status was obtained from the Polish National Death Registry. ResultsUsing Cox proportional hazard analysis, performed for all individuals with lung cancer, the hazard ratio (HR) for death from all causes was 1.25 (95% CI: 0.86–1.83, P = 0.99) for patients in the lowest tertile compared to those in the highest tertile of serum selenium levels. Among the patients with stage I disease this relationship was significant (HR-2.73; P = 0.01) for selenium level in tertile 1 (<57 μg/L) compared to tertile 3 (>69 μg/L, reference). The 80 months crude survival after diagnosis was 79.5% (95% CI: 68.5–92.4%) for individuals in the highest tertile and 58.1% (95% CI: 45.1–74.9%) for individuals in the lowest tertile with stage I lung cancer. ConclusionThese results suggest that in patients undergoing treatment for stage I lung cancer, serum selenium levels at the time of diagnosis (>69 μg/L) may be associated with improved overall survival.

Cancer-cell-secreted CXCL11 promoted CD8+ T cells infiltration through docetaxel-induced-release of HMGB1 in NSCLC

BackgroundChemotherapy combined with immunotherapy becomes the main trend in lung cancer intervention; however, how chemotherapy promotes the immune function remains elusive. Therefore, we sought to determine how chemotherapy promotes the immune function.MethodsWe determined in 100 NSCLC patients the expression of CD8, functional markers (IFN-γ, Granzyme B, and Perforin) and specific chemokines by quantitative real-time reverse transcriptase-PCR. Functional experiments were carried out to check whether docetaxel (DOC), a chemotherapeutic agent, modifies the expression of HMGB1 and CXCL11, and influences the infiltration properties of CD8+ T cells to the tumor microenvironment. The mechanism of the release of HMGB1 and CXCL11 was determined by flow cytometry, immunofluorescence and western blotting. In in vivo experiment, we confirmed how DOC enhanced the recruitment of HER2-CAR T cells to tumor sites.ResultsWe found that DOC upregulated the expression of chemokine receptor ligand CXCL11 in tumor microenvironment and subsequently enhanced CD8+ T cell recruitment. DOC treatment significantly increased HMGB1 release in an ROS-dependent manner. Recombinant protein HMGB1 stimulated the secretion of CXCL11 via NF-κB activation in vitro. Tumors from DOC-treated mice exhibited higher expression of HMGB1 and CXCL11, more HER2-CAR T cell infiltration, and reduced progression, relative to control. Increased HMGB1 and CXCL11 expressions were positively correlated with prolonged overall survival of lung cancer patients.ConclusionsOur results demonstrate that DOC induces CD8+ T cell recruitment to the tumor microenvironment by enhancing the secretion of HMGB1 and CXCL11, thus improving the anti-tumor efficacy, indicating that modulating the HMGB1-CXCL11 axis might be helpful for NSCLC treatment.

Stomatin plays a suppressor role in non-small cell lung cancer metastasis

ObjectiveMetastasis is one of the key causes of high mortality in lung cancer. Aberrant DNA methylation is a common event in metastatic lung cancer. We aimed to identify new epigenetic regulation of metastasis-associated genes and characterize their effects on lung cancer progression.MethodsWe screened genes associated with non-small cell lung cancer (NSCLC) metastasis by integrating datasets from the Gene Expression Omnibus (GEO) database. We obtained epigenetic-regulated candidate genes by analyzing the expression profile of demethylation genes. By overlapping analysis, epigenetically modulated metastasis-associated genes were obtained. Kaplan-Meier plotter (KM plotter) was utilized to assess the overall survival (OS) of stomatin in lung cancer. Immunohistochemistry (IHC) was conducted to determine the association between stomatin and metastasis-associated clinical indicators. Both in vitro and in vivo assays were performed to investigate the potential role of stomatin in metastasis. The regulation mechanisms of transforming growth factor β1 (TGFβ1) on stomatin were determined by Sequenom MassARRAY quantitative methylation and western blot assays. ResultsA series of bioinformatic analyses revealed stomatin as the metastasis-associated gene regulated by DNA methylation. The KM plotter analysis showed a positive association between stomatin and the OS of lung cancer. IHC analysis indicated that the decreased stomatin expression is linked with advanced TNM stage. Loss- and gain-of-function experiments displayed that stomatin could inhibit the migration and invasion of NSCLC cells. Furthermore, TGFβ1 repressed stomatin expression during epithelial-to-mesenchymal transition (EMT). The negative correlation between stomatin and TGFβ1 was also validated in advanced stage III lung tumor samples. The underlying mechanism by which TGFβ1 inhibits stomatin is due in part to DNA methylation.ConclusionsOur results suggest that stomatin may be a target for epigenetic regulation and can be used to prevent metastatic diseases.

Expression and prognosis analyses of forkhead box A (FOXA) family in human lung cancer

Despite advances in early diagnosis and treatment, cancer still remains the major reason of mortality worldwide. The forkhead box A (FOXA) family is reported to participate in diverse human diseases. However, little is known about their expression and prognostic values in human lung cancer. Herein, we conducted a detailed cancer vs. normal analysis. The mRNA expression levels of FOXA family in numerous kind of cancers, including lung cancer, were analyzed using the Oncomine and GEPIA database. We observed that the mRNA expression levels of FOXA1, and FOXA3 were all increased while FOXA2 were decreased in most cancers compared with normal tissues, especially in lung cancer. Moreover, the expression levels of FOXA1, and FOXA3 are also highly expressed, while FOXA2 were decreased in almost all cancer cell lines, particularly in lung cancer cell lines, analyzing by Cancer Cell Line Encyclopedia (CCLE) and EMBL-EBI databases. Furthermore, the LinkedOmics database was used to evaluate the prognostic values, indicating that higher expression of FOXA1, FOXA3 indicated a poor overall survival (OS), while increased FOXA2 revealed a better OS in lung cancer. To conclusion, FOXA family showed significant expression differences between cancer and normal tissues, especially lung cancer, and FOXA1, FOXA3 could be promising prognostic biomarkers for lung cancer.

Prognostic value of prognostic nutritional index in lung cancer: a meta-analysis.

Previous studies reported pretreatment prognostic nutritional index (PNI) was associated with clinical outcome of lung cancer. However, the result was not conclusive. We conducted a comprehensive meta-analysis to clarify the impact of PNI in lung cancer prognosis. We identified eligible studies by searching PubMed, EMBASE, and Web of Science, up to August 15, 2017. Overall survival (OS) and clinicopathological characteristics were collected from included studies. Pooled hazard ratios (HR) and corresponding 95% confidence intervals (CIs) were used to estimate clinical and prognostic value of PNI in lung cancer. Ten studies including 5,085 patients were enrolled in the meta-analysis. The result demonstrated that low PNI was correlated with unfavorable OS in lung cancer (HR =1.72; 95% CI, 1.43-2.06; P=0.000), especially among non-small cell lung cancer patients (HR =1.93; 95% CI, 1.56-2.37; P=0.000). As for clinical characteristics, low PNI status was found related to gender (female versus male, HR =0.68; 95% CI, 0.554-0.857; P=0.001) and histology (adenocarcinoma versus non-adenocarcinoma, HR =0.59; 95% CI, 0.47-0.74, P=0.000), but not smoking status (smoker versus never smoker, HR =1.49; 95% CI, 0.99-2.25, P=0.056). No significant publication bias was found (P=0.210). PNI was an independent prognostic indicator for lung cancer, and can serve as a novel biomarker to help guide clinical practice and promote clinical outcomes of lung cancer patients.

The prognostic significance of hTERT overexpression in cancers: A systematic review and meta-analysis.

Background:Human telomerase reverse transcriptase (hTERT) plays an important role in cancer progression. Recently, several clinical studies investigated how the overexpression of hTERT predicts the poor prognosis of solid tumors. However, the results were inconclusive, partly because of the small numbers of patients included.Method:We systematically searched PubMed, Web of Science, and Embase to identify relevant studies until August 2017. Hazard ratios (HRs) with 95% confidence intervals (CIs) were used to evaluate the association of hTERT expression and survival outcomes.Results:A total of 27studies enrolling 2530 solid tumor patients were included in this meta-analysis. There were strong significant associations between hTERT overexpression and all endpoints: overall survival (OS) (HR = 1.50, 95% CI: 1.31–1.73, P = .00), disease-free survival (HR = 1.84, 95% CI: 1.38–2.46; P = .00), and recurrence-free survival (HR = 1.79, 95% CI: 1.07–2.99; P = .028). In the subgroup analysis, it was found that the overexpression of hTERT induced poor OS in lung cancer (HR = 1.51, 95% CI: 1.21–1.89; P = .00).Conclusion:Our comprehensive systematic review concluded that the overexpression of hTERT was associated with poor survival in human solid tumors. hTERT may be a valuable predictive biomarker for prognosis.

Prognostic significance of CXCL5 expression in cancer patients: a meta-analysis

BackgroundCXCL5 is a member of the CXC-type chemokine family, which has been found to play important roles in tumorigenesis and cancer progression. Recent studies have demonstrated that CXCL5 could serve as a potential prognostic biomarker for cancer patients. However, the prognostic value of CXCL5 is still controversial.MethodsWe systematically searched PubMed, Embase and Web of Science to obtain all relevant articles investigating the prognostic significance of CXCL5 expression in cancer patients. Hazards ratios (HR) with corresponding 95% confidence intervals (CI) were pooled to estimate the association between CXCL5 expression levels with survival of cancer patients.ResultsA total of 15 eligible studies including 19 cohorts and 5070 patients were enrolled in the current meta-analysis. Our results demonstrated that elevated expression level of CXCL5 was significantly associated with poor overall survival (OS) (pooled HR 1.70; 95% CI 1.36–2.12), progression-free survival (pooled HR 1.65; 95% CI 1.09–2.49) and recurrence-free survival (pooled HR 1.49; 95% CI 1.15–1.93) in cancer patients. However, high or low expression of CXCL5 made no difference in predicting the disease-free survival (pooled HR 0.63; 95% CI 0.11–3.49) of cancer patients. Furthermore, we found that high CXCL5 expression was associated with reduced OS in intrahepatic cholangiocarcinoma (HR 1.91; 95% CI 1.31–2.78) and hepatocellular carcinoma (HR 1.87; 95% CI 1.55–2.27). However, there was no significant association between expression level of CXCL5 with the OS in lung cancer (HR 1.25; 95% CI 0.79–1.99) and colorectal cancer (HR 1.16; 95% CI 0.32–4.22, p = 0.826) in current meta-analysis.ConclusionsIn conclusion, our meta-analysis suggested that elevated CXCL5 expression might be an adverse prognostic marker for cancer patients, which could help the clinical decision making process.

Bioinformatic analysis of prognostic value of ZW10 interacting protein in lung cancer.

BackgroundZWINT is a crucial component of the mitotic checkpoint. However, its possible role in lung cancer is unclear. In this study, we determined its correlation with lung cancer.MethodsReal-time PCR and immunohistochemistry (IHC) were used to determine 40 collected clinical lung cancer samples. Chi-square test was used to examine possible correlations between ZWINT expression and clinicopathological factors. The prognostic significance of mRNA expression of ZWINT in lung cancer was evaluated using the Kaplan–Meier plotter. Univariate and multivariate Cox proportional hazards regression analysis were performed to determine whether ZWINT is an independent risk factor for overall survival (OS) and disease-free survival (DFS) of lung cancer patients. Additionally, STRING database was used to analyze protein-protein interactions.ResultsIn this study, we screened 13 GSE datasets and detected that ZWINT is highly expressed in multiple carcinomas including lung, melanoma, prostate, nasopharyngeal, gastric, pancreatic, colon, esophageal, ovarian, renal, breast and liver cancer. Real-time PCR and IHC results of collected clinical lung cancer samples confirmed that ZWINT is highly expressed in tumor tissues compared with adjacent non-tumor tissues. Additionally, high expression of ZWINT might predict poor OS and DFS in lung cancer patients. Moreover, disease stage and expression level of ZWINT were correlated with recurrence-free survival and OS in lung cancer. Analysis of protein-protein interaction based on STRING database gained 8 top genes which could interact with ZWINT, including PMF1, MIS12, DSN1, ZW10, BUB1, BUB1B, CASC5, NDC80, NSL1 and NUF2.ConclusionZWINT is aberrantly highly expressed in lung tumor tissues and might be involved in the pathogenesis of lung cancer.

Prognostic value of increased integrin-beta 1 expression in solid cancers: a meta-analysis.

Integrin-beta 1 (ITGB1) is aberrantly overexpressed or downregulated in solid cancers; however, its prognostic value remains controversial. Therefore, we conducted a meta-analysis to explore whether ITGB1 expression is correlated with overall survival (OS) and the clinicopathological characteristics of patients with solid cancers. We systematically searched the PubMed, Embase, and Web of Science databases for eligible studies published up to June 1, 2017. In total, 22 studies involving 3,666 patients were included. A sensitivity analysis was performed to assess the validity and reliability of the pooled OS. Among the 22 studies, 7 focused on lung cancer, 3 focused on colorectal cancer, 6 focused on breast cancer, 3 involved melanoma, and 3 involved pancreatic cancer. The pooled results showed that high ITGB1 expression was significantly associated with worse OS in lung cancer (pooled hazard ratio [HR]=1.78, 95% CI: 1.19–2.65, p<0.05) and breast cancer (pooled HR=1.88, 95% CI: 1.46–2.42, p<0.01). In addition, a significant association was observed between high ITGB1 expression and disease-free survival in breast cancer (pooled HR=1.63, 95% CI: 1.17–2.25, p<0.001) and pancreatic cancer (pooled HR=2.49, 95% CI: 1.35–4.61, p<0.001). However, high ITGB1 expression was not related to OS in colorectal cancer, pancreatic cancer, or melanoma. The pooled HRs used to evaluate the prognostic value of increased ITGB1 expression in lung cancer, breast cancer, and pancreatic cancer were not significantly altered, which indicates that the pooled results were robust. The results of this study indicate that the prognostic value of decreased ITGB1 expression varies among solid cancers.

Prognostic Value of Plasma Fibrinogen in Lung Cancer Patients: A Meta-Analysis

Background: The prognostic role of plasma fibrinogen in lung cancer remains controversial. The aim of this meta-analysis was to assess the prognostic value of plasma fibrinogen in lung cancer.Methods: We performed a systematic literature search to identify eligible studies in PubMed, Embase and the Cochrane Library database. The hazard ratios (HR) and their 95% confidence intervals (CI) were collected from these eligible studies and were used to assess the relationship between plasma fibrinogen and lung cancer.Results: A total of 16 studies including 6,881 patients were selected in this meta-analysis. The results showed that elevated plasma fibrinogen in lung cancer patients was correlated with poor overall survival (OS) (HR = 1.38, 95% CI: 1.22-1.55, P < 0.001) and disease-free survival (DFS) / progress-free survival (PFS). (HR = 1.29, 95% CI: 1.01-1.65, P = 0.042). When stratified by cut-off value for OS and DFS/PFS, there was no significant heterogeneity. And the results of “cut-off value ≥ 400mg/dl” group showed that the high level of fibrinogen in serum was associated with worse OS and DFS/PFS of lung cancer. In further subgroup analysis by tumor histology, high plasma fibrinogen was also associated with worse OS in non-small cell lung cancer (NSCLC) (HR = 1.32, 95% CI: 1.14-1.53, P < 0.001). However, there was no significant association between high plasma fibrinogen and poor DFS in NSCLC patients (HR = 1.24, 95% CI: 0.97-1.57, P = 0.08). The Egger's regression test indicated evidence of publication bias for DFS/PFS.Conclusions: Elevated plasma fibrinogen, particularly defined as a plasma fibrinogen concentration of ≥ 400mg/dl, could be a promising indicator for worse OS in lung cancer patients, including NSCLC.

Mutant-allele fraction heterogeneity is associated with non-small cell lung cancer patient survival.

Genetic intratumor heterogeneity is associated with tumor occurrence, development and overall outcome. The present study aims to explore the association between mutant-allele fraction (MAF) heterogeneity and patient overall survival in lung cancer. Somatic mutation data of 939 non-small cell lung cancer (NSCLC) cases were obtained from The Cancer Genome Atlas. Entropy-based mutation allele fraction (EMAF) score was used to describe the uncertainty of individual somatic mutation patterns and to further analyze the association with patient overall survival. Results indicated that association between EMAF and overall survival was significant in the discovery set [hazard ratio (H)R=1.62; 95% confidence interval (CI): 1.08–2.41; P=0.018] and replication set (HR=1.63; 95% CI: 1.11–2.37; P=0.011). In addition, EMAF was also significantly different in lung adenocarcinoma and squamous cell carcinoma. Furthermore, a significant difference was indicated in early-stage patients. Results from c-index analysis indicated that EMAF improved the model predictive performance on the 3-year survival beyond that of traditional clinical staging, particularly in early-stage patients. In conclusion, EMAF successfully reflected MAF heterogeneity among patients with NSCLC. Additionally, EMAF improved the predictive performance in early-stage patient prognosis beyond that of traditional clinical staging. In clinical application, EMAF appears to identify a subset of early-stage patients with a poor prognosis and therefore may help inform clinical decisions regarding the application of chemotherapy after surgery.