The Relationship Between Age And Prognosis Of Colorectal Cancer And Its Mechanism

Part1:The prognostic significance of age in operated and non-operated colorectal cancerBackground:The prognostic significance of age in colorectal cancer remains controversial.Our purpose was to determine the impact of age at diagnosis on cause-specific survival and overall survival in patients with colorectal cancer.Methods:Using Surveillance,Epidemiology,and End Results(SEER)population-based data,we identified 226,430 patients with colorectal cancer diagnosed between 1996 and 2005.Patients were separated into 10-year age groups.Five-year cancer cause-specific survival and overall survival data were obtained.Kaplan-Meier methods were adopted and multivariable Cox regression models were built for the analysis of long-term survival outcomes and risk factors.Results:In the operated group,those aged 51-60 had the best prognosis with 5-year cause-specific survival of 72.3%and 5-year overall survival of 68.3%.In the non-operated group,those of young age 15-30 had the best prognosis with 5-year cause-specific survival of 21.2%and 5-year overall survival of 18.2%,and there was continued worsening in cause-specific survival and overall survival with increasing age,except for a small increase in the 51-60 age group(P<0.001).Multivariable analysis demonstrated a statistically significant disadvantage in cause-specific survival in patients older than 60(P<0.001),but the difference between the 51-60 age group and the younger age group(15-30,31-40,41-50)wasn’t statistically significant(P>0.05)in both operated and non-operated patients.Conclusions:There was no apparent difference in survival in colorectal cancer patients 60 and younger,but in those older than 60 years,there was worsening in overall survival and cause-specific survival in both operated and nonoperated patients.Part2:Preliminary study of difference gene expression patterns between young and elder colorectal cancer patientsBackground:Our previous study indicated that young patients with colorectal cancer had better cause specific survival than those in elder ones with cutoff value of 60,but the exact mechanism is unknown.We hypothesized that this difference may be caused by inherit difference of gene expressions.In this section,we used the The Cancer Genome Atlas(TCG A)to screen the candidate genes that were differently expressed between young and elder patients,and bioinformatics analysis were used to investigate the functional role of different expressed genes.Methods:We downloaded colorectal cancer RNA sequence database in TCGA database from University of California Santa Cruz(UCSC)website(https://genome-cancer.ucsc.edu/),and divided patients into young and elder groups with cutoff value of 60.Propensity score matching was used to normalize the baseline of the two groups.t test was used to find the differently expressed genes.GO(Gene Ontology)and KEGG(Kyoto Encyclopedia of Genes and Genomes,KEGG)were used to study the gene function.Results:After propensity score matching,133 patients were included in each group in TCGA database,and one hundred ten differently expressed genes were identified using t test.Molecular function of GO analysis indicated that these differently expressed genes were correlated with Vitamin binding,sequence-specific DNA binding,sodium ion binding,transcriptional factor activities,and so on.Biological process analyses found the differently expressed genes were associated with anatomical structure formation involved in morphogenesis,response to drug,sodium ion transport,neuropeptide signaling pathway,wnt signaling pathway,nervous system development,cAMP-mediated signaling,and so on.Cellular component analyses demonstrated that the differently expressed genes were correlated with cell fraction,secretory granules,membrane fraction,insoluble fraction,cell junction,extracellular region,and so on.KEGG analyses further indicated that the differently expressed genes were correlated with glycine,serine and threonine metabolism,Type I diabetes mellitus,alanine,aspartate and glutamate metabolism,Vitamin digestion and absorption,biosynthesis of unsaturated fatty acids,cysteine and methionine metabolism.Conclusion:There were series of differently expressed genes between young and elder patients with colorectal cancer,and these differently expressed genes were involved in series of vital pathological process,such as sensitivity to drug,transcriptional factor activities,ion transports,wnt signal pathway,amino acid and unsaturated fatty acids metabolism.A further study was needed to investigate the functional of these differently expressed genes.