| ObjectiveOur study analyzed the ADH/ALDH gene family by using the TCGA database and the KM plotter database to explore the diagnostic and prognostic value of the ADH/ALDH gene family in gastric cancer.Materials and MethodsThe clinical data of gastric cancer TCGA was downloaded from the UCSC Xena database,and RNA sequencing data was downloaded from the TCGA database.Unpaired t-test was used to compare the m RNA expression of gastric cancer and adjacent tissues in TCGA database.The scatter plot and ROC curve of cancer and adjacent cancer were drawn.The univariate survival analysis and multivariate Cox regression model survival analysis were used to analyze ADH/ALDH gene expression and clinical survival time in gastric cancer of TCGA cohort,clinical pathological parameters were analyzed by subgroup analysis;finally,the prognostic relationship between ADH/ALDH gene family and gastric cancer was verified in the Kaplan–Meier plotter(KM plotter) database.ResultsAfter the expression of ADH/ALDH m RNA in 375 cases of gastric cancer and 32 cases of adjacent tissues by function Log2,the results of independent sample t test showed that ADH1 B,ADH1C,ADH4,ADH5,ADH7,ALDH1A1,ALDH1A2,ALDH1L1,ALDH2,ALDH3A1,ADH3B2,ALDH4A1,ALDH6A1,ALDH7A1,ALDH8A1 and ALDH9A1 m RNA expression levels were lower than those in adjacent tissues.The unilateral analysis of 351 cases of gastric cancer with ADH/ALDH m RNA expression in TCGA database showed that the survival time of patients with high expression of ALDH4A1 and ALDH5A1 m RNA was significantly higher than that of low expression,P=0.027,P=0.031.Age,TNM stage,body tumor burden,radiotherapy,radical degree of surgery and molecular targeted therapy were corrected as P<0.05,multivariate Cox regression analysis showed that high ALDH4A1 and ALDH5A1 m RNA expression longer survival time compared with low expression,HR,0.65;95% CI,0.43-0.96;P=0.032 and HR,0.53;95% CI,0.35-0.80;P=0.003,respectively.The survival analysis of KM plotter database ADH/ALDH gene m RNA showed that ALDH4A1(Affymetrix ID: 211552_s_at)and ALDH5A(Affymetrix ID: 1203609_s_at)high expression with gastric cancer patients,had a longer survival time than low expression;HR : 0.78;95% CI,0.65-0.95;P = 0.012 and HR: 0.78,95% CI,0.63-0.96;P = 0.018 respectively.Conclusions1.The m RNA expression levels of ADH1 B,ADH1C,ADH4,ADH5,ADH7,ALDH1A1,ALDH1A2,ALDH1L1,ALDH2,ALDH3A1,ADH3B2,ALDH4A1,ALDH6A1,ALDH7A1,ALDH8A1 and ALDH9A1 were lower than those in adjacent tissues,which may inhibit in the development of gastric cancer2.The survival time of patients with high expression of ALDH4A1/ALDH5A1 m RNA in TCGA database and KM plotter database is longer than that of low expression,and confirmed at the genetic level that it has inhibitory effect on the occurrence and development of gastric cancer.ObjectiveThe ALDH4A1/ALDH5A1 who was screened out with related to the prognosis of gastric cancer,was analyze by the immunohistochemical with gastric cancer cases in the affiliated tumor hospital of Guangxi Medical University,was carried out to determine the correlation of clinical diagnosis and prognosis of gastric cancer.Materials and MethodsThe gastric cancer cases with complete clinical pathological prognosis data were collected from the Affiliated Tumor Hospital of Guangxi Medical University.Immunohistochemistry was used to detect the expression of ALDH4A1/ALDH5A1 and prognosis in gastric cancer and adjacent tissues,the independent sample t test was used to compare the differences.The scatter plot and or ROC plot were plotted to compare the tissue staining intensity score,staining positive cell rate score and semi-quantitative score.Finally,the survival analysis of these genes in gastric cancer tissues was performed.Results161 cases of gastric cancer tissue and 36 cases of normal tissue adjacent were stained with ALDH4A1/ALDH5A1 staining intensity,staining positive cell rate score and semi-quantitative score were analyzed to independent sample t test and draw scatter plot,P>0.05.In the unilateral analysis,the positive expression of ALDH4A1 in patients with gastric cancer was longer than that of the negative ones,P=0.031;corrected tumor location,tissue differentiation,TNM staging,chemotherapy(P<0.05),multivariate Cox model survival analysis showed,the survival time of patients with positive ALDH4A1 immunohistochemical expression in gastric cancer cases was not statistically significant(P=0.598),but it tended to be positive that the survival time of the expression was longer(HR,0.82;95% CI,0.39-1.72);the positive survival time of ALDH5A1 immunohistochemical expression in gastric cancer showed no difference in statistical significance.ConclusionsThe positive expression of ALDH4A1 in gastric cancer patients was longer than that of the negative ones.At the protein level,it was further confirmed that it inhibited the development of gastric cancer.ObjectiveIn order to further understanding the function of ADH and ALDH genes in gastric cancer,the third part of this study screened out ALDH4A1 gene related to the prognosis of gastric cancer according to the first and second parts,made a target and prospective exploration of their functions in gastric cancer by using bioinformatics tools.Materials and MethodsCo-expressed genes in gastric cancer tissues were screened using TCGA genome-wide expression profiling data and Pearson correlation analysis with ALDH4A1 gene.These co-expressed genes were then used for functional enrichment analysis of Gene ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)on DAVID,and STRING and Gene MANIA were used to verify the interaction of these genes.Finally,in the TCGA genome-wide data of gastric cancer,the high/low expression of the selected genes was grouped and analyzed by single gene of Gene Set Enrichment Analysis(GSEA).ResultsCorrelation analysis between TCGA genome-wide expression profiles and ALDH4A1 Pearson showed that 782 genes were co-expressed with ALDH4A1 in gastric cancer tissues.GO Term analysis of ALDH4A1 and its co-expressed gene in TCGA genome of gastric cancer showed that it participates in protecting cells from oxidative stimulation,protein binding,regulation of cell migration,extracellular secretion,GTPase-mediated signal transduction,etc.The results of KEGG functional enrichment analysis showed that they were involved in signal pathways such as Hippo,Rap1 and Wnt.The co-expression network of ALDH4A1 and its co-expressed genes in the TCGA genome of gastric cancer showed that the ALDH4A1 has complex direct or indirect interactions with its co-expressed genes on the STRING website and Gene MANIA analysis.The single-gene GSEA analysis of ALDH4A1 in TCGA genome-wide data of gastric cancer showed that,compared with low expression,the high expression of ALDH4A1 in the c5 data set and its tumor tissue was enriched to play NAD(P)+ dependent enzymes to protect biological organs from oxidative stimulation,damage and mismatch repair,maintaining DNA replication stability,silencing genes and other functions,indicating that ALDH4A1 high expression has anti-tumor function.Compared with low expression,high expression of ALDH4A1 in the c2 dataset and its tumor tissues were enriched with mismatch repair,negative regulation of tumor metastasis,down-regulation of EGFR signal,down-regulation of MYC and TFRC signaling,indicating that high expression of ALDH4A1 inhibited tumor growth and metastasis.ConclusionsALDH4A1 gene in gastric cancer TCGA genome-wide expression profile data correlation analysis,co-expression analysis,enrichment function showed that a large number of genes with the same or opposite expression levels play a complex gene function of repair,regulation,transduction,protection,etc.The development of gastric cancer may be co-regulated by multiple gene or signal pathways.The ALDH4A1 gene plays an inhibitory role in the development of gastric cancer. |
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