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An age stratified analysis of the biomarkers in patients with colorectal cancer

ABSTRACT: Colorectal cancer (CRC), a common malignant tumor of the digestive tract, has a high incidence and mortality rate. Several recent studies have found that aging is associated with the increasing risk of cancer. Nevertheless, the expression status and function of age-related genes in CRC is still not well understood. In the study, we comprehensively analyzed the gene expression data of CRC patients from The Cancer Genome Atlas (TCGA) database. Age-related differential expression genes (age-related DEGs) in tumor tissues compared with normal tissues of CRC were further identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of age-related DEGs were performed by clusterProfiler of R. Afterwards, we used the STRING database to map the protein–protein interaction network of DEGs. We constructed prognostic model through univariate and multivariate COX regression analyses, and further evaluated their predictive power. The prognostic gene signature-related functional pathways were explored by gene set enrichment analysis (GSEA). The weighted gene co-expression network analysis (WGCNA) was used to identify key module associated with two prognostic gene signatures. Finally, we used the Metascape to perform functional enrichment analysis of genes in the key module. A total of 279 age-related DEGs were identified from the TCGA database. GO and KEGG enrichment analysis showed that the age-related DEGs were enriched in the Modulation of chemical synaptic transmission and Neuroactive ligand–receptor interaction. Moreover, we established a novel age-related gene signature (DLX2 and PCOLCE2) for overall survival in CRC, which was further predicted in both the training and validation sets. The results of GSEA demonstrated that numerous disease-related pathways were enriched in the high-risk group. We identified 43 genes related to the DLX2 and PCOLCE2 by the WGCNA co-expression network. We also found that these 43 genes were enriched in the cancer-related pathways. To sum up, the study identified an age-related gene signature for predicting the prognosis of CRC patients, which is conducive to the identification of novel prognostic molecular markers.

SUBMITTER: Yao H

PROVIDER: S-EPMC8599678 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundOlder adults comprise 40% of surgical inpatients and are at increased risk of postoperative rehospitalization. A decade ago, 30-day rehospitalizations for Medicare patients were reported as 15%, and more than 70% was attributed to medical causes. In the interim, there have been several large-scale efforts to establish best practice for older patients through surgical quality programs and national initiatives by Medicare and the National Health Service. To understand the current state of rehospitalization in the USA, we sought to report the incidence and cause of 30-day rehospitalization across surgical types by age.Study designWe performed a retrospective study utilizing the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) dataset from 2015 to 2019. Our primary exposure of interest was age. Patients were categorized into four groups: 18-49, 50-64, 65-74, and 75 + years old. Reasons for rehospitalization were evaluated using NSQIP defined causes and reported International Classification of Disease (ICD)-9 and ICD-10 codes. Our primary outcome was the incidence of unplanned 30-day rehospitalization and secondary outcome the cause for rehospitalization. Variables were summarized by age group through relative (%) and absolute (n) frequencies; chi-square tests were used to compare proportions. Since rehospitalization is a time-to-event outcome in which death is a competing event, the cumulative incidence of rehospitalization at 30 days was estimated using the procedure proposed by Gray. The same strategy was used for estimating the cumulative incidence for unplanned rehospitalizations.ResultsA total of 2,798,486 patients met inclusion criteria; 198,542 had unplanned rehospitalization (overall 7.09%). Rehospitalization by age category was 6.12, 6.99, 7.50, and 9.50% for ages 18-49, 50-64, 65-74, and 75 + , respectively. Complications related to the digestive system were the single most common cause of rehospitalization across age groups. Surgical site infection was the second most common cause, with the relative frequency decreasing with age as follows: 21.74%, 19.08%, 15.09%, and 9.44% (p < .0001). Medical causes such as circulatory or respiratory complications were more common with increasing age (2.10%, 4.43%, 6.27%, 8.86% and 3.27, 4.51, 6.07, 8.11%, respectively).ConclusionWe observed a decrease in overall rehospitalization for older surgical patients compared to studies a decade ago. The oldest (≥ 75) surgical patients had the highest 30-day rehospitalization rates (9.50%). The single most common reason for rehospitalization was the same across age groups and likely attributed to surgery (ileus). However, the aggregate of medical causes of rehospitalization was more common in older patients; surgical and respiratory reasons were twice as common in this group. Rehospitalization increased by age for some surgery types, e.g., lower extremity bypass, more than others, e.g., ventral hernia repair. Future investigations should focus on interventions to reduce medical complications and further decrease postoperative rehospitalization for older surgical patients undergoing high-risk procedures.

Project description:PurposeTo provide resource-stratified, evidence-based recommendations on the treatment and follow-up of patients with early-stage colorectal cancer.MethodsASCO convened a multidisciplinary, multinational Expert Panel that reviewed existing guidelines and conducted a modified ADAPTE process and a formal consensus process with additional experts for one round of formal ratings.ResultsExisting sets of guidelines from 12 guideline developers were identified and reviewed; adapted recommendations from six guidelines form the evidence base and provide evidence to inform the formal consensus process, which resulted in agreement of 75% or more on all recommendations.RecommendationsFor nonmaximal settings, the recommended treatments for colon cancer stages nonobstructing, I-IIA: in basic and limited, open resection; in enhanced, adequately trained surgeons and laparoscopic or minimally invasive surgery, unless contraindicated. Treatments for IIB-IIC: in basic and limited, open en bloc resection following standard oncologic principles, if not possible, transfer to higher-level facility; in emergency, limit to life-saving procedures; in enhanced, laparoscopic en bloc resection, if not possible, then open. Treatments for obstructing, IIB-IIC: in basic, resection and/or diversion; in limited or enhanced, emergency surgical resection. Treatment for IIB-IIC with left-sided: in enhanced, may place colonic stent. Treatment for T4N0/T3N0 high-risk features or stage II high-risk obstructing: in enhanced, may offer adjuvant chemotherapy. Treatment for rectal cancer cT1N0 and cT2n0: in basic, limited, or enhanced, total mesorectal excision principles. Treatment for cT3n0: in basic and limited, total mesorectal excision, if not, diversion. Treatment for high-risk patients who did not receive neoadjuvant chemotherapy: in basic, limited, or enhanced, may offer adjuvant therapy. Treatment for resectable cT3N0 rectal cancer: in enhanced, base neoadjuvant chemotherapy on preoperative factors. For post-treatment surveillance, a combination of medical history, physical examination, carcinoembryonic antigen testing, imaging, and endoscopy is performed. Frequency depends on setting. Maximal setting recommendations are in the guideline. Additional information can be found at www.asco.org/resource-stratified-guidelines .NoticeIt is the view of the American Society of Clinical Oncology that health care providers and health care system decision makers should be guided by the recommendations for the highest stratum of resources available. The guidelines are intended to complement but not replace local guidelines.

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An age stratified analysis of the biomarkers in patients with colorectal cancer

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