Distinct Prognostic Value Research Articles

Distinct expression and prognostic value of OTU domain-containing proteins in non-small-cell lung cancer.

The ubiquitin-proteasome pathway is an important protein degradation regulatory system in cells. This pathway is also a reversible process that is strictly regulated, and the regulation of deubiquitinating enzymes (DUBs) represents an important facet of the process. Ovarian tumor-associated proteases domain-containing proteins (OTUDs), as a subfamily within the DUB family, serve an important role in regulatory mechanisms of several biological processes, through the regulation of gene transcription, cell cycle, immune response, inflammation and tumor growth processes, and may be important in the diagnosis of various diseases and constitute novel drug targets. However, the role of OTUDs in non-small-cell lung cancer (NSCLC) has not been fully elucidated. In the present study, the Oncomine database was used to examine gene expression in NSCLC, and the prognostic value of each gene was analyzed by Kaplan-Meier analysis. The results indicated that high mRNA expression levels of OTUD1, OTUD3, OTUD4 and putative bifunctional UDP-N-acetylglucosamine transferase and deubiquitinase ALG13 were associated with improved prognosis in all NSCLC and adenocarcinoma, but not in squamous cell carcinoma. By contrast, high expression levels of OTUD2 mRNA were associated with poorer overall survival in patients with NSCLC. These data suggested that these OTUD isozymes may be a potential drug target for NSCLC.

AKR1C1-3, notably AKR1C3, are distinct biomarkers for liver cancer diagnosis and prognosis: Database mining in malignancies.

Aldo-keto reductases, known as AKR1C1-AKR1C4 enzymes, are pivotal to NADPH-dependent reduction, and their expression is highly associated with the progression of malignant cancers. However, the expression and distinct prognostic value of the AKR1C family members in liver cancer are not well established. In the current study, the expression of AKR1C isoforms was studied using the Oncomine online databases. In addition, their expression profiles were analyzed in cancer cell lines using data from the Cancer Cell lines Encyclopedia (CCLE) database. Furthermore, the mRNA expression levels of AKR1C family members between liver cancer and normal liver samples were assessed by the Gene Expression Profiling Interactive Analysis (GEPIA) database. The AKR1C1-3 prognostic value was further investigated by the Kaplan-Meier plotter database in liver cancer patients. It was found that the expression levels of AKR1C3 were elevated significantly in liver cancer tissues and cells as demonstrated by the Oncomine, CCLE and GEPIA databases. The expression levels of AKR1C1 and AKR1C2 in liver cancer tissues did not increase significantly in the Oncomine database while expression was significantly high in CCLE and GEPIA databases. However, the expression levels of the AKR1C4 gene as determined by the CCLE, GEPIA and Oncomine databases were not consistent. Therefore, the Kaplan-Meier survival curves of liver cancer patients with the expression of AKR1C1-3 genes were next analyzed. The data indicated that high expression levels of AKR1C1-3 were correlated with lower overall survival in liver cancer patients. Using the co-expression and PPI network, AKR1C1-3 genes were identified that were involved in the same pathway displaying 44 total unique interactors. These results suggested that the increased AKR1C1-3, notably AKR1C3 expression levels served as possible diagnostic biomarkers and essential prognostic factors for liver cancer patients. The roles of AKR1C4 in liver cancer require further examination.

Distinct prognostic value of circulating anti-telomerase CD4+ Th1 immunity and exhausted PD-1+/TIM-3+ T cells in lung cancer

BackgroundDespite the critical roles of Th1-polarised CD4+ T cells in cancer immunosurveillance, the translation of their potential to clinical use remains challenging. Here, we investigate the clinical relevance of circulating antitumor Th1 immunity in non-small cell lung cancer (NSCLC).MethodsThe circulating antitumor Th1 response was assessed by the ELISpot assay in 170 NSCLC patients using a mixture of HLA class II-restricted peptides from telomerase (TERT). Phenotyping of blood immune cells was performed by flow cytometry.ResultsTERT-reactive CD4 T-cell response was detected in 35% of NSCLC patients before any treatment. Functional analysis showed that these cells were effector memory and Th1 polarised capable to produce effector cytokines, such as IFN-γ, TNF-α and IL-2. The presence of anti-TERT Th1 response was inversely correlated with the level of exhausted PD-1+/TIM-3+CD4 T cells. The level of these two immune parameters differentially affected the survival, so that increased level of anti-TERT Th1 response and low rate of exhausted PD-1+TIM-3+CD4+ T cells were associated with a better prognosis.ConclusionsSystemic anti-TERT Th1 response plays a strong antitumor protective role in NSCLC. This study underlines the potential interest of monitoring circulating antitumor Th1 response for patients’ stratification and therapy decision.

MiR-362-3p is downregulated by promoter methylation and independently predicts shorter OS of cervical squamous cell carcinoma

The current study was undertaken to investigate the potential influence of methylation on miR-362-5p/3p expression and further analyzed their independent prognostic value in cervical adenocarcinoma (ADC) and squamous cell carcinoma (SCC) respectively. SiHa and CaSki cells were used as the in vitro cell model. In silico bioinformatic analysis was conducted via the combined use of the Cancer Genome Atlas-Cervical Cancer (TCGA-CESC), Starbase 3.0 and String 10.5. Results revealed that the downregulation of miR-362-5p/3p was accompanied by the infection of high-risk human papillomavirus (HR-HPV) and their expression was further decreased in HR-HPV cancer tissues. Demethylation could restore their expression. By performing Methylation-specific PCR (MSP) based on methylated or unmethylated specific primers, we confirmed that the proximal promoter region was methylated in both cell lines. Higher miR-362-3p expression might independently predict favorable overall survival (OS) in SCC patients (HR: 0.561, 95%CI: 0.354−0.889, p = 0.014), after adjustment of clinical stages, lymphovascular invasion and miR-362-5p expression. However, no prognostic value of miR-362-5p or miR-362-3p expression was observed in terms of OS in patients with ADC. Via bioinformatic analysis, we found that miR-362-3p might have an entirely different regulatory network in cervical ADC and SCC, which might help to explain the distinct prognostic value of miR-362-3p in these two histological subtypes. In summary, we infer that the methylation level of the proximal promoter region of pre-miR-362 would influence the expression of miR-362-5p/3p in cervical cancer. MiR-362-3p expression might be a specific prognostic biomarker in cervical SCC, but not in ADC.

E2F2/5/8 Serve as Potential Prognostic Biomarkers and Targets for Human Ovarian Cancer.

E2Fs are a family of pivotal transcription factors. Accumulative evidence indicates that aberrant expression or activation of E2Fs is a common phenomenon in malignances, and significant associations have been noted between E2Fs and tumorigenesis or progression in a wide range of cancers. However, the expression patterns and exact roles of each E2F contributing to tumorigenesis and progression of ovarian cancer (OC) have not yet been elucidated. In this study, we investigated the distinct expression and prognostic value of E2Fs in patients with OC by analyzing a series of databases, including ONCOMINE, GEPIA, cBioPortal, Metascape, and Kaplan–Meier plotter. The mRNA expression levels of E2F1/3/5/8 were found to be significantly upregulated in patients with OC and were obviously associated with tumor stage for OC. Aberrant expression of E2F2/5/7/8 was found to be associated with the clinical outcomes of patients with OC. These results suggest that E2F2/5/8 might serve as potential prognostic biomarkers and targets for OC. However, future studies are required to validate our findings and promote the clinical utility of E2Fs in OC.

Correlation of Ki-67 Index with Volumetric Segmentation and its Value as a Prognostic Marker in Glioblastoma

Previous research has shown a strong correlation between the Ki-67 proliferation index and grade of malignancy in astrocytoma. Ki-67 has also shown encouraging results as a prognostic marker for patients' overall survival (OS). We focus on whether the index is linked to the appearance of glioblastoma on pretreatment magnetic resonance imaging (MRI) or to OS. In our retrospective study, only isocitrate dehydrogenase IDH wild-type glioblastoma was included (n= 152). Ki-67 index was quantified via immunohistochemistry. On all pretreatment MRI, tumor compartments (tumor, necrosis, and edema) were volumetrically assessed. An OS subpopulation was filtered from the total cohort (residual tumor volume ≤2 cm3). In addition, a propensity score matching was executed. All volumetric assessed tumor volumes correlated with each other (P ≤ 0.011), although the Ki-67 index showed no correlation with any of the measured volumes. Concerning the OS, a cutoff value of 20% for the Ki-67 index showed a significant influence on patients' OS in multivariate analysis (P= 0.043). The unique appearance of every glioblastoma on MRI seems to be independent of the Ki-67 index. Furthermore, the Ki-67 index did show a distinct prognostic value for OS within our cohort at a cutoff value of 20% for Ki-67.

Expression of Demethylase Genes, FTO and ALKBH1, Is Associated with Prognosis of Gastric Cancer

BackgroundReversible N6-methyladenosine (m6A) modifications in messenger RNAs can be categorized under the field of “RNA epigenetics.” However, the potential role of m6A-related genes in gastric cancer (GC) prognosis has not been systematically researched.AimsThis study was aimed at providing insights into the prognostic role of m6A-related gene expression, at both mRNA and protein levels.MethodsKaplan–Meier (KM) plotter database and The Cancer Genome Atlas (TCGA) database were used to explore the prognostic significance of individual m6A-related genes in overall survival (OS) and progression-free survival at the mRNA level. For independent validation, the protein level of genes significantly associated with prognosis in both databases was further detected in 450 paired GC and corresponding adjacent non-tumor tissues using tissue microarray (TMA)-based immunohistochemistry (IHC). The relationship between the FTO and ALKBH1 expression and the clinicopathological characteristics was explored.ResultsAmong nine m6A-related genes, aberrantly high mRNA expression of FTO and ALKBH1 was associated with poor OS in the KM and TCGA cohorts. However, the TMA-IHC indicated that protein expression of FTO and ALKBH1 was markedly downregulated in GC tissues. A lower protein level of ALKBH1 was closely correlated with larger tumor sizes (≥ 5 cm) and more advanced TNM stages, while lower FTO protein expression was associated with shorter OS in GC patients.ConclusionsAberrant expression of demethylase genes, FTO and ALKBH1, has a distinct prognostic value in GC patients, indicating that FTO and ALKBH1 may play vital roles in GC progression and metastasis.

Distinct expression and prognostic value of members of the epidermal growth factor receptor family in ovarian cancer.

BackgroundIncreased aberrant expression or activation of the epidermal growth factor receptor (EGFR) family members has been reported in a wide range of cancers, and the EGFR family of tyrosine kinases has emerged as an important therapeutic target in malignancies. However, the expression patterns and exact roles of each distinct EGFR family member, which contribute to tumorigenesis and progression of ovarian cancer (OC), are yet to be elucidated.Materials and methodsIn the current study, we report the distinct expression and prognostic value of EGFR family members in patients with OC by analyzing a series of databases including ONCOMINE, Gene Expression Profiling Interactive Analysis, Kaplan–Meier plotter, cBioPortal, and Database for Annotation, Visualization and Integrated Discovery .ResultsIt was found that in patients with OC, mRNA expression levels of ERBB2/3/4 were significantly upregulated, whereas the transcription levels of EGFR were downregulated. Aberrant EGFR expression and ERBB2/3/4 mRNA levels were associated with OC prognosis.ConclusionThese results suggest that EGFR and ERBB3/4 are distinct prognostic biomarkers and may be potential targets for OC. These results may be beneficial to better understand the molecular underpinning of OC and may be useful to develop tools for more accurate OC prognosis and for promoting the development of EGFR-targeted inhibitors for OC treatment.

Distinct prognostic value of dynactin subunit 4 (DCTN4) and diagnostic value of DCTN1, DCTN2, and DCTN4 in colon adenocarcinoma.

BackgroundColon adenocarcinoma (COAD) is ranked as the third most commonly diagnosed cancer in both women and men, and it is the most frequently occurring malignant tumor. Dynactin is a protein compound based on multiple subunits, including dynactin 1–6 (DCTN1–6), in most categories of cytoplasmic dynein performance in eukaryotes. Nevertheless, correlations between the DCTN family and the prognosis and diagnosis of COAD remain unidentified.MethodsStatistics for DCTN mRNA expression in patients with COAD were acquired from The Cancer Genome Atlas. Kaplan–Meier analyses and a Cox regression model were applied to determine overall survival, with computation of HRs and 95% CIs. Several online data portals were used to assess the biological process, and pathway examination was performed using the Kyoto Encyclopedia of Genes and Genomes to predict the biological functionality of DCTN genes.ResultsWe found that high expression of DCTN4 was linked with satisfactory results for overall survival (P=0.042, HR=0.650, 95% CI 0.429–0.985). The expression of DCTN1, DATN2, and DCTN4 was closely correlated with the frequency of colon tumors (P<0.001, area under the curve [AUC]=0.8811, 95% CI 0.8311–0.9312; P<0.001, AUC=0.870, 96% CI 0.833–0.9071; and P=0.0051, AUC=0.6317, 95% CI 0.5725–0.6908, respectively). In the enrichment examination, the level of gene expression was related to the cell cycle, cell apoptosis, and the cell metastasis pathway.ConclusionThe expression levels of DCTN1, DCTN2, and DCTN4 could allow differentiation between cancer-bearing tissues and paracancerous tissue. These genes can be applied as biomarkers to predict the prognosis and diagnosis of COAD.

Distinct Expression and Prognostic Value of MS4A in Gastric Cancer.

Gastric cancer has high malignancy and early metastasis, which lead to poor survival rate. In this study, we assessed the expressions and prognostic values of MS4A family, a newly recently discovered family, by two online dataset, GEPIA and Kaplan Meier-plotter. From these results eight members, MS4A2, MS4A6, MS4A7, MS4A8, MS4A14, MS4A15, TMEM176A and TMEM176B showed positive expression in gastric cancer or normal tissues, and these genes were screened for further analysis of prognostic values. We observed that low mRNA expressions of MS4A2, MS4A7, MS4A14, MS4A15, TMEM176A and TMEM176B were correlated with better overall survival (OS) in all gastric cancer patients, while high mRNA expression of MS4A6 was observed to be associated with good prognosis. MS4A8’s high mRNA level was correlated to better OS in diffuse gastric cancer patients. Further, we estimated prognostic values of MS4A family in gastric cancer patients with different clinic-pathological features, including clinical stages, differentiation level, lymph node status and HER2 status. Our results indicate that these eight MS4A members can estimate prognosis in patients with different pathological groups. In conclusion, MS4A family members are potential biomarkers, and may contribute to tumor progression in gastric cancer.

Total metabolic tumor volume, circulating tumor cells, cell-free DNA: distinct prognostic value in follicular lymphoma

AbstractOutcomes for follicular lymphoma (FL) have greatly improved, but most patients will ultimately relapse. High total metabolic tumor volume (TMTV), computed from baseline 18F-fluorodeoxyglucose–positron emission tomography (PET), is associated with shorter progression-free survival (PFS), but circulating tumor cells (CTCs) and cell-free DNA (cfDNA) may also reflect tumor burden and be of prognostic value. The aim of our study was to correlate CTCs and cfDNA with TMTV in FL at diagnosis and to determine their prognostic values. We retrospectively analyzed 133 patients (with previously untreated FL and a baseline PET) from 2 cohorts with either a baseline plasma sample (n = 61) or a bcl2-JH-informative peripheral blood (PB) sample (n = 68). Quantification of circulating bcl2-JH+ cells and cfDNA was performed by droplet digital polymerase chain reaction. A significant correlation was found between TMTV and both CTCs (P < .0001) and cfDNA (P < .0001). With a median 48-month follow-up, 4-year PFS was lower in patients with TMTV > 510 cm3 (P = .0004), CTCs >0.0018 PB cells (P = .03), or cfDNA >2550 equivalent-genome/mL (P = .04). In comparison with TMTV alone, no additional prognostic information was obtained by measuring CTCs. In contrast, Cox multivariate analysis, including cfDNA and TMTV, showed that both cfDNA and TMTV remained predictive of outcome. In conclusion, CTCs and cfDNA correlate with TMTV in FL, and all 3 influence patient outcome. PFS was shorter for patients with high cfDNA and TMTV, suggesting that these parameters provide relevant information for tumor-tailored therapy.

Distinct prognostic value of mRNA expression of guanylate-binding protein genes in skin cutaneous melanoma.

The purpose of the present study was to assess if guanylate-binding protein (GBP) mRNAs could be prognostic biomarkers for patients with skin cutaneous melanoma (SKCM). The prognostic value of GBP mRNA expression in patients with SKCM was investigated by analyzing gene expression data in 459 SKCM patients. The data were extracted from the OncoLnc database of The Cancer Genome Atlas. A high expression of GBP1, GBP2, GBP3, GBP4 and GBP5 were correlated with favorable overall survival (OS) in the SKCM patients followed for over 30 years. In addition, a high expression of GBP6 mRNA was not correlated with OS in the SKCM patients. A joint effects analysis showed that the co-incidence of the high expression of GBP1-5 was correlated with favorable overall survival in SKCM patients. Our findings suggest that GBP1-5 mRNAs in SKCM are associated with favorable prognosis and may be potential prognostic biomarkers. The combination of GBP1-5 could improve the sensitivity for predicting OS in SKCM patients.

Prognosis Analysis of Histone Deacetylases mRNA Expression in Ovarian Cancer Patients.

Histone deacetylases modulate the dynamic balance of histone acetylation and deacetylation in cells, which participate in epigenetic regulations. Accumulated evidence has demonstrated that histone deacetylases are associated with angiogenesis, cell proliferation and survival in a variety of human cancers. However, the expression and distinct prognostic value of histone deacetylases in ovarian cancer have not been well elucidated. In the present study, we collected the overall survival (OS), progress free survival (PFS), and histone deacetylases (HDAC1-11) mRNA expression in ovarian cancer from the Kaplan-Meier plotter online database. We investigated the relationship between histone deacetylases mRNA level and the clinicopathological parameters of the ovarian cancer patients, such as histology subtypes, clinical stages, grades and TP53 mutation. Our analysis data showed that over-expression of HDAC1, HDAC2, HDAC4, HDAC5 and HDAC11 were correlated to poor overall survival and unfavorable progress free survival in all ovarian cancer patients. Notably, the higher level of HDAC11 was associated with the worse OS and PFS for serous/ stage III+IV/ grade III/ TP53 mutation ovarian cancer patients. In conclusion, HDACs may play a crucial role in the prognosis of ovarian cancer, but it is worth noting that HDAC11 may be a biomarker for poor prognosis in ovarian cancer patients.

Expression and potential mechanism of metabolism-related genes and CRLS1 in non-small cell lung cancer.

Cardiolipin (CL) is a phospholipid localized in the mitochondria, which is essential for mitochondrial structure and function. Human cardiolipin synthase 1 (CRLS1) is important in regulating phosphatidylglycerol (PG) remodeling and CL biosynthesis. However, the expression and distinct prognostic value of CRLS1 in neoplasms, including non-small cell lung cancer (NSCLC), is not well established. In the present study, the mRNA expression of CRLS1 was investigated using Oncomine analysis and the prognostic value was assessed using the Kaplan-Meier plotter database for patients with NSCLC. The results of the analyses indicated that the expression of CRLS1 in lung cancer was lower, compared with that in normal lung tissues. Notably, a high expression of CRLS1 was found to be associated with improved overall survival (OS) in all patients with NSCLC and lung adenocarcinoma (Ade). However, this was not observed in patients with squamous cell carcinoma (SCC). The results also demonstrated an association between the mRNA expression of CRLS1 and the clinicopathological parameters of patients with NSCLC, including sex, smoking status, tumor grade, clinical stage, lymph node status and chemotherapy. These results indicated that CRLS1 was associated with improved prognosis in patients with NSCLC, particularly at an early stage (T1N1M0). In addition, it was revealed that CRLS1 was co-expressed with well-known genes associated with metabolism using Gene Ontology term enrichment analysis. Kyoto Encyclopedia of Genes and Genomes pathway analysis also showed that tumor-related metabolism and the mitogen-activated protein kinase (MAPK) signaling pathways were enriched with CRLS1-co-expression genes. The results of the present study suggested that CRLS1 may be a novel tumor suppressor involved in regulating lipid and seleno-amino acid metabolism in the tumor microenvironment, and suppressing the MAPK signaling pathway during tumorigenesis and development. Comprehensive evaluation of the expression, prognosis and potential mechanism of CRLS1 is likely to promote an improved understanding of the complexity of the molecular biology of NSCLC.

Systems analysis identifies melanoma-enriched pro-oncogenic networks controlled by the RNA binding protein CELF1

Melanomas are well-known for their altered mRNA expression profiles. Yet, the specific contribution of mRNA binding proteins (mRBPs) to melanoma development remains unclear. Here we identify a cluster of melanoma-enriched genes under the control of CUGBP Elav-like family member 1 (CELF1). CELF1 was discovered with a distinct prognostic value in melanoma after mining the genomic landscape of the 692 known mRBPs across different cancer types. Genome-wide transcriptomic, proteomic, and RNA-immunoprecipitation studies, together with loss-of-function analyses in cell lines, and histopathological evaluation in clinical biopsies, revealed an intricate repertoire of CELF1-RNA interactors with minimal overlap with other malignancies. This systems approach uncovered the oncogene DEK as an unexpected target and downstream effector of CELF1. Importantly, CELF1 and DEK were found to represent early-induced melanoma genes and adverse indicators of overall patient survival. These results underscore novel roles of CELF1 in melanoma, illustrating tumor type-restricted functions of RBPs in cancer.

Altered capicua transcriptional repressor gene expression exhibits distinct prognostic value for isocitrate dehydrogenase-mutant oligodendroglial tumors.

To evaluate the prognostic significance of the altered expression of capicua transcriptional repressor (CIC) in isocitrate dehydrogenase (IDH)-mutant oligodendroglial tumors, a cohort of 54 IDH-mutant oligodendroglial tumors (designated as the Xijing cohort) were examined by immunohistochemistry (IHC), and two public expression data sets from The Cancer Genome Atlas (TCGA; n=265) and the Gene Expression Omnibus (GEO; n=45) were analyzed in the present study. The prognostic value was evaluated by survival analysis and Cox hazards models. Overall survival (OS) was investigated with Kaplan-Meier curves and log-rank tests. Gene set enrichment analysis (GSEA) was also performed to characterize the functional profiles of each subgroup. It was revealed that in IDH-mutant, 1p/19q co-deleted oligodendroglial tumors, higher CIC expression (at mRNA and protein levels) was associated with a more favorable OS time (log-rank P-values: TCGA, P=0.034; GEO, P=0.012; Xijing cohort, P=0.029). By contrast, among IDH-mutant, 1p/19q intact tumors, higher CIC expression was associated with poorer OS time (log-rank P-values: TCGA, P=0.007; GEO, P=0.017; Xijing cohort, P=0.012). To the best of our knowledge, this is the first study demonstrating the distinct prognostic value of altered CIC expression with regard to the 1p/19q status among IDH-mutant oligodendroglial tumors. The dual roles of CIC may be influenced by its transcriptional regulatory activity and the consequent functional profiles. Additionally, a simple risk classification scheme based on CIC expression alone is proposed for the optimal prediction of prognosis in patients with oligodendroglial tumors.

Mining expression and prognosis of topoisomerase isoforms in non-small-cell lung cancer by using Oncomine and Kaplan-Meier plotter.

DNA topoisomerases are essential to modulate DNA topology during various cellular genetic processes. The expression and distinct prognostic value of topoisomerase isoforms in non-small-cell lung cancer (NSCLC) is not well established. In the current study, we have examined the mRNA expression of topoisomerase isoforms by using Oncomine analysis and investigated their prognostic value via the Kaplan–Meier plotter database in NSCLC patients. Our analysis indicated that the expression level of topoisomerases in lung cancer was higher compared with normal tissues. Especially, high expression of two topoisomerase isoforms, TOP2A and TOP3A, was found to be correlated to worse overall survival (OS) in all NSCLC and lung adenocarcinoma (Ade) patients, but not in lung squamous cell carcinoma (SCC) patients. In a contrast, high expression of isoforms TOP1 and TOP2B indicated better OS in all NSCLC and Ade, but not in SCC patients. Meanwhile, high expression of TOP1MT and TOP3B was not correlated with OS in NSCLC patients. Furthermore, we also demonstrated a relationship between topoisomerase isoforms and the clinicopathological features for the NSCLC patients, such as grades, clinical stages, lymph node status, smoking status, gender, chemotherapy and radiotherapy. These results support that TOP2A and TOP3A are associated with worse prognosis in NSCLC patients. In addition, our study also shows that TOP1 and TOP2B contribute to favorable prognosis in NSCLC patients. The exact prognostic significance of TOP1MT and TOP3B need to be further elucidated. Comprehensive evaluation of expression and prognosis of topoisomerase isoforms will be a benefit for the better understanding of heterogeneity and complexity in the molecular biology of NSCLC, paving a way for more accurate prediction of prognosis and discovery of potential drug targets for NSCLC patients.

Baseline and On-Treatment Markers Determining Prognosis of First-Line Chemotherapy in Combination with Bevacizumab in Patients with Metastatic Colorectal Cancer

Background: In metastatic colorectal cancer, no upfront or on-treatment markers are available to determine the prognosis or efficacy for chemotherapy in combination with bevacizumab. Patients and Methods: The current analysis was performed to evaluate the prognostic value of disease and patient characteristics (age, number of metastatic sites, stage of primary tumor, performance status, carcinoembryonic antigen (CEA)) and on-treatment changes of CEA (response after 8-12 weeks of treatment and specific patterns of CEA kinetics) in patients from an observational cohort study of chemotherapy with bevacizumab. Results: Baseline factors were available from 1,438 patients. Patients with baseline CEA levels > 20 ng/ml, more than 1 metastatic site, and age > 75 years showed significantly lower progression-free (PFS) and overall survival in multivariate analysis. A CEA response of > 30% during treatment was associated with increased PFS. In addition, the pattern of CEA kinetics predicts survival and response to treatment. Conclusion: In summary, baseline CEA, number of metastatic sites, and age are strong independent prognostic factors for survival. By monitoring CEA, clear patterns with distinct prognostic value can be determined. CEA kinetics and/or response after 8-12 weeks might be a useful and simple tool to stratify the post-induction treatment approach based on individual prognosis in the future.

Prognostic value of the full-scale Periapical Index.

To evaluate whether the full-scale Periapical Index (PAI) can predict the periapical status over time in nonroot filled and root filled teeth. Full-mouth radiographic surveys of a random sample from a general population were performed in 1997, 2003 and 2008. The present investigation included 330 persons who participated in all three examinations and 143 persons who participated in the first and second examination. At each examination, the presence or absence of a tooth and of a root filling was recorded, and a PAI score (1-5) was assigned to all teeth. Retreatment of a root filling was recorded for root filled teeth. Statistical analysis was carried out using ordinal logistic regression and logistic regression and computed as Wald's tests. At baseline, nonroot filled teeth had lower PAI scores than root filled teeth (P < 0.0001). A high baseline PAI increased the risk of extraction for both root filled (P < 0.001) and nonroot filled teeth (P < 0.001). At 5-year follow-up, PAI scores were higher when baseline PAI scores had been higher. The overall pattern for root filled and nonroot filled teeth was similar, however, the differences were statistically significant (P < 0.001). In particular, the follow-up PAI score for nonroot filled teeth with baseline PAI score 1 or 2 was significantly lower than that of root filled teeth (P < 0.001). For root filled teeth with baseline PAI score 3, 4 or 5, the trend was reversed as they overall had slightly lower PAI scores at follow-up (P = 0.023). Repeated radiographic assessments of teeth using the full-scale PAI reveal that each of the five scores had distinct prognostic value for the course of periapical disease over a 5-year period for both nonroot filled and root filled teeth.

Prognostic Value of CD166 Expression in Cancers of the Digestive System: A Systematic Review and Meta-Analysis

ObjectiveMany studies have reported the prognostic predictive value of CD166 as a cancer stem cell marker in cancers of the digestive system; however, its predictive value remains controversial. Here, we investigate the correlation between CD166 positivity in digestive system cancers and clinicopathological features using meta-analysis.MethodsA comprehensive search in PubMed and ISI Web of Science through March of 2013 was performed. Only articles containing CD166 antigen immunohistochemical staining in cancers of the digestive system were included,including pancreatic cancer, esophageal cancer, gastric cancer and colorectal cancer. Data comparing 3- and 5-year overall survival along with other clinicopathological features were collected.ResultsNine studies with 2553 patients who met the inclusion criteria were included for the analysis. The median rate of CD166 immunohistochemical staining expression was 56% (25.4%–76.3%). In colorectal cancer specifically, the results of a fixed-effects model indicated that CD166-positive expression was an independent marker associated with a smaller tumor burden (T category; RR = 0.93, 95%, CI: 0.88–0.98) but worse spread to nearby lymph nodes (N category; RR = 1.17, 95% CI: 1.05–1.30). The 5-year overall survival rate was showed relationship with cytoplasmic positive staining of CD166 (RR = 1.47 95% 1.21–1.79), but no significant association was found in the pool or any other stratified analysis with 3- or 5- year overall survival rate.ConclusionBased on the published studies, different cellular location of CD166 has distinct prognostic value and cytoplasmic positive expression is associated with worse prognosis outcome. Besides, our results also find CD166 expression indicate advanced T category and N-positive status in colorectal cancer specifically.