A number of studies have revealed that there is an increasing incidence of early-onset colorectal cancer (CRC) in young adults (before the age of 50 years) and a progressive decline in CRC among older patients, after the age of 50 years (late-onset CRC). However, the etiology of early-onset CRC is not fully understood. The aim of the present study was to identify key genes associated with the development of early-onset CRC through weighted gene co-expression network analysis (WGCNA). The GSE39582 dataset was downloaded from the Gene Expression Omnibus database, and the data profiles of tissues from patients diagnosed before the age of 50 years were selected. The top 10,000 genes with the highest variability were used to construct the WGCNA. Hub genes were identified from the modules associated with clinical traits using gene significance >0.2 and module membership >0.8 as the cutoff criteria. Gene Ontology and pathway analyses were subsequently performed on the hub genes and a protein-protein interaction network (PPI) was constructed. The diagnostic value of module hub genes with a degree score >5 in the PPI network was verified in samples from patients with CRC diagnosed before the age of 50 years obtained from The Cancer Genome Atlas. Eight co-expressed gene modules were identified in the WGCNA and two modules (blue and turquoise) were associated with the tumor-node-metastasis stage. A total of 140 module hub genes were identified and found to be enriched in 'mitochondrial large ribosomal subunit', 'structural constituent of ribosome', 'poly (A) RNA binding', 'collagen binding', 'protein ubiquitination' and 'ribosome pathway'. Twenty-six module hub genes were found to have a degree score >5 in the PPI network, seven of which [secreted protein acidic and cysteine rich (SPARC), decorin (DCN), fibrillin 1 (FBN1), WW domain containing transcription regulator 1 (WWTR1), transgelin (TAGLN), DEAD-box helicase 28 (DDX28) and cold shock domain containing C2 (CSDC2)], had good prognostic values for patients with early-onset CRC, but not late-onset CRC. Therefore, SPARC, DCN, FBN1, WWTR1, TAGLN, DDX28 and CSDC2 may contribute to the development of early-onset CRC and may serve as potential diagnostic biomarkers.

No abstract

Neutral endopeptidase (NEP/CD10) and dipeptidyl peptidase IV (DPP IV/CD26) are both ubiquitous glycopeptidases which play important roles in tumor pathogenesis and development. The aim of this study was to investigate the expression patterns and the prognostic significance of CD10 and CD26 in osteosarcoma patients. CD10 and CD26 expression in 116 pairs of primary osteosarcoma and corresponding noncancerous bone tissue samples from the same specimens were detected by immunohistochemistry. The Spearman's correlation was calculated between the expression levels of CD10 and CD26 in osteosarcoma tissues. The associations of CD10 and CD26 expression with the clinicopathologic features and with the prognosis of osteosarcoma were subsequently assessed. Both CD10 expression and CD26 expression in osteosarcoma tissues were significantly higher than those in corresponding noncancerous bone tissue samples (both P < 0.001). Overexpression of CD10 and CD26 were respectively observed in 68.10 % (79/116) and 70.69 % (82/116) of osteosarcoma tissues. A significant correlation was found between CD10 expression and CD26 expression in osteosarcoma tissues (r = 0.83, P < 0.001). In addition, combined overexpression of CD10 and CD26 was observed in 52.59 % (61/116) of osteosarcoma tissues. CD10-high/CD26-high expression was significantly correlated with advanced clinical stage (P = 0.001), positive metastatic status (P = 0.001), shorter overall (P < 0.001) and disease-free (P < 0.001) survival in patients with osteosarcomas. Furthermore, multivariate survival analysis showed that clinical stage, metastatic status, CD10 expression, CD26 expression and combined expression of CD10/CD26 were all independent prognostic factors for predicting both overall and disease-free survival of osteosarcoma patients. Interestingly, combined expression of CD10/CD26 had a better prognostic value than other features. This retrospective study offer the convincing evidence for the first time that the overexpression of CD10 or CD26 may be an important feature of human osteosarcomas, and the combined expression of CD10/CD26 may be an efficient prognostic indicator for this disease.