Long Non-coding RNA HOTAIR for Tumor Diagnosis and Pathological Staging

LncRNA HOTAIR has different expression levels in different stages of tumorigenesis and development.Therefore,it has potential application in clinical diagnosing tumor stage as a tumor marker.Fifty patients with lung cancer and fifty healthy volunteers were selected as lung cancer group and control group respectively.According to T and N stage of cancer,the patients were divided into T1,T2,T3 and N0,N1,N2 groups.Fluorescence in situ hybridization(FISH)was used to detect the expression of HOTAIR in lung cancer tissues and paraneoplastic tissues.The expression levels of NSE,CEA and CYFRA21-1 in serum were detected by immunofluorescence.The results showed that the expression level of HOTAIR in paraneoplastic tissues(0.98±0.04)were significantly lower than that in lung cancer tissues(3.56±0.15).The serum levels of NSE,CEA and CYFRA21-1 of the lung cancer group were higher than those in the control group.The concentrations of HOTAIR,NSE,CEA and CYFRA21-1 increased with the progress of clinical stages,which indicated that the expression of HOTAIR was positively correlated with the expression of SE,CEA and CYFRA21-1.These results indicate that HOTAIR,NSE,CEA and CYFRA21-1 are associated with the initiation and development of tumors.Therefore,HOTAIR combined with tumor marker can improve the accuracy of detection of pathological stage of lung cancer.

Identification of Prognostic Genes for Colon Cancer through Gene Coexpression Network Analysis

Objective:The present study was aimed to identify novel key genes,prognostic biomarkers and molecular pathways implicated in tumorigenesis of colon cancer.Methods:The microarray data GSE41328 containing 10 colon cancer samples and 10 adjacent normal tissues was analyzed to identify 4763 differentially expressed genes.Meanwhile,another microarray data GSE17536 was performed for weighted gene co-expression network analysis(WGCNA).Results:In present study,12 co-expressed gene modules associated with tumor progression were identified for further studies.The red module showed the highest association with pathological stage by Pearson's correlation analysis.Functional enrichment analysis revealed that genes in red module focused on cell division,cell proliferation,cell cycle and metabolic related pathway.Then,a total of 26 key hub genes were identified,and GEPIA database was subsequently selected for validation.Holliday junction-recognizing protein(HJURP)and cell division cycle 25 homolog C(CDC25C)were identified as effective prognosis biomarkers,which were all detrimental to prognosis.Gene set enrichment analyses(GSEA)found the two hub genes were enriched in“oocyte meiosis”,“oocyte maturation that are progesterone-mediated”,“p53 signaling pathway”,and“cell cycle”.Furthermore,the immunohistochemistry and western blotting showed that HJURP was highly expressed in colon cancer tissue.Conclusion:HJURP was identified as a key gene associated with colon cancer progression and prognosis by WGCNA,which might influence the prognosis by regulating cell cycle pathways.

Proposal and validation of a modified staging system to improve the prognosis predictive performance of the 8th AJCC/ UICC pTNM staging system for gastric adenocarcinoma: a multicenter study with external validation

Background:The 8th edition of the American Joint Committee on Cancer/Union for International Cancer Control(AJCC/UICC)pathological tumor-node-metastasis(pTNM)staging system may have increased accuracy in predicting prognosis of gastric cancer due to its important modifications from previous editions.However,the homogeneity in prognosis within each subgroup classified according to the 8th edition may still exist.This study aimed to compare and analyze the prognosis prediction abilities of the 8th and 7th editions of AJCC/UICC pTNM staging system for gastric cancer and propose a modified pTNM staging system with external validation.Methods:In total,clinical data of 7911 patients from three high-capacity institutions in China and 10,208 cases from the Surveillance,Epidemiology,and End Results(SEER)Program Registry were analyzed.The homogeneity,discrimina-tory ability,and monotonicity of the gradient assessments of the 8th and 7th editions of AJCC/UICC pTNM staging system were compared using log-rank χ^(2),linear-trend χ^(2),likelihood-ratioχ2 statistics and Akaike information criterion(AIC)calculations,on which a modified pTNM classification with external validation using the SEER database was proposed.Results:Considerable stage migration,mainly for stage III,between the 8th and 7th editions was observed in both cohorts.The survival rates of subgroups of patients within stage IIIA,IIIB,or IIIC classified according to both editions were significantly different,demonstrating poor homogeneity for patient stratification.A modified pTNM staging system using data from the Chinese cohort was then formulated and demonstrated an improved homogeneity in these abovementioned subgroups.This staging system was further validated using data from the SEER cohort,and similar promising results were obtained.Compared with the 8th and 7th editions,the modified pTNM staging system displayed the highest log-rank χ^(2),linear-trend χ^(2),likelihood-ratio χ^(2),and lowest AIC values,indicating its superior discriminatory ability,monotonicity,homogeneity and prognosis prediction ability in both populations.Conclusions:The 8th edition of AJCC/UICC pTNM staging system is superior to the 7th edition,but still results in homogeneity in prognosis prediction.Our modified pTNM staging system demonstrated the optimal stratification and prognosis prediction ability in two large cohorts of different gastric cancer populations.

Considerations on the role of environmental toxins in idiopathic Parkinson’s disease pathophysiology

Neurodegenerative diseases are characterized by a progressive dysfunction of the nervous system.Often associated with atrophy of the affected central or peripheral nervous structures,they include diseases such as Parkinson’s Disease(PD),Alzheimer’s Disease and other dementias,Genetic Brain Disorders,Amyotrophic Lateral Sclerosis(ALS or Lou Gehrig’s Disease),Huntington’s Disease,Prion Diseases,and others.The prevalence of neurodegenerative diseases has increased over the last years.This has had a major impact both on patients and their families and has exponentially increased the medical bill by hundreds of billions of Euros.Therefore,understanding the role of environmental and genetic factors in the pathogenesis of PD is crucial to develop preventive strategies.While some authors believe that PD is mainly genetic and that the aging of the society is the principal cause for this increase,different studies suggest that PD may be due to an increased exposure to environmental toxins.In this article we review epidemiological,sociological and experimental studies to determine which hypothesis is more plausible.Our conclusion is that,at least in idiopathic PD(iPD),the exposure to toxic environmental substances could play an important role in its aetiology.