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Study for relationship between baseline lactic acid level and prognosis of patients with colorectal cancer

ABSTRACT: Interventions: Hyperuricemia group:No;Non-hyperlactateemia group:No Primary outcome(s): Overall survival;Progression-free survival Study Design: Factorial

DISEASE(S): Colorectal Cancer

PROVIDER: 2739575 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Project description:BackgroundGlioma is the most common type of intracranial tumor with high malignancy and poor prognosis despite the use of various aggressive treatments. Targeted therapy and immunotherapy are not effective and new biomarkers need to be explored. Some Procollagen-lysine 2-oxyglutarate 5-dioxygenase (PLOD) family members have been found to be involved in the metastasis and progression of tumors. Both PLOD2 and PLOD3 had been reported to be highly expressed in gliomas, while the prognostic value of PLOD1 remains to be further illustrated, so we want to investigate the PLOD1 expression in glioma and its clinical implication.MethodsWe collected gene expression and corresponding clinical data of glioma from the Chinese Glioma Genome Atlas (CGGA) database, The Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) database. First, we analyzed the expression and mutation of PLOD1 in gliomas and its relationship with clinicopathologic characteristics. Then, we conducted survival analysis, prognostic analysis and nomogram construction of the PLOD1 gene. Finally, we conducted gene ontology (GO) enrichment analysis and gene set enrichment analysis (GSEA) to explore possible mechanisms and gene co-expression analysis was also be performed.ResultsThe results showed that the expression level of PLOD1 was higher in gliomas than normal tissues, and high expression of PLOD1 was related to poor survival which can serve as an oncogenic factor and an independent prognostic indicator for glioma patients. Both the GO and GSEA analysis showed high expression of PLOD1 were enriched in Extracellular matrix (ECM) related pathways, the co-expression analysis revealed that PLOD1 was positively related to HSPG2, COL6A2, COL4A2, FN1, COL1A1, COL4A1, CD44, COL3A1, COL1A2 and SPP1, and high expression of these genes were also correlated to poor prognosis of glioma.ConclusionsThe results showed that high expression of PLOD1 leads to poor prognosis, and PLOD1 is an independent prognostic factor and a novel biomarker for the treatment of glioma. Furthermore, targeting PLOD1 is most likely a potential therapeutic strategy for glioma patients.

Project description:Background: Penicillins inhibit cell wall synthesis; therefore, H. pylori must be dividing for these antibiotics to be effective. Identifying growth responses to varying medium pH may allow design of more effective treatment regimens. Aim: To determine the effect of acidity on bacterial growth and the bactericidal efficacy of ampicillin. Methods: H. pylori were incubated in dialysis chambers suspended in 1.5L of media at various pHs with 5mM urea, with or without ampicillin, for 4, 8 or 16 hours, thus mimicking unbuffered gastric juice. Changes in gene expression, viability and survival were determined. The bacterial load of H. pylori infected gerbils was determined with and without profound acid inhibition. Results: At pH 3.0, but not at pH 4.5 or 7.4, there was decreased expression of ~400 genes, including many cell envelope biosynthesis, cell division genes and penicillin-binding proteins. In the presence of ampicillin, viability and survival declined at pH 4.5 and 7.4 but not at pH 3.0. Profound acid inhibition of H. pylori infected gerbils increased the antral bacterial load >3 fold, showing that elevation of intragastric pH stimulated growth. Conclusions: Ampicillin is bactericidal at pH 4.5 and 7.4, but not at pH 3.0, due to decreased expression of cell envelope and division genes at pH 3.0. Therefore, at pH 3.0, the pH at the gastric surface, the bacteria are non-dividing and persist with ampicillin treatment. A more effective inhibitor of acid secretion that maintains gastric pH near neutrality for 24 hours/day should enhance the efficacy of triple therapy and of amoxicillin, even allowing dual therapy for H. pylori eradication. There were a total of three biological replicates, each containing one control (incubated at pH 7.4) and one acidic (pH 3.0) sample, whose RNA were extracted on different dates. Microarray studies performed on these six samples were done in triplicate. One of the triplicates for two of the biological control triplicates were removed from the data set due to poor hybridization

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Study for relationship between baseline lactic acid level and prognosis of patients with colorectal cancer

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