DEFB4A is a potential prognostic biomarker for colorectal cancer

Abstract

Colorectal cancer (CRC) is the third leading cause of cancer-associated mortality. The present study aimed to investigate novel biomarkers to predict prognosis and provide a theoretical basis for studies of the pathogenesis and the development of therapies for CRC. The present study compared mRNA expression levels of patients with CRC with short- and long-term prognosis and of individuals with and without tumors in The Cancer Genome Atlas (TCGA) database. Differentially expressed genes (DEGs) were identified via volcano plot and Venn diagram analysis. Gene Ontology (GO) analysis and gene set enrichment analysis (GSEA) were performed to identify the functions of the DEGs, and the DEGs were further verified using clinical CRC samples. A total of 10 DEGs were identified as candidate genes using the TCGA database, and four DEGs [defensin β 4A ( DEFB4A ), hyaluronan binding protein 2 ( HABP2 ), oleoyl-ACP hydrolase and TBC1 domain family member 3G] were associated with poor prognosis of patients with CRC. Two DEGs ( DEFB4A and HABP2 ) were upregulated in tumor tissues of patients with CRC in the TCGA database. GO and GSEA analyses revealed that DEFB4A was highly associated with immunosuppression, participates in ‘myeloid leukocyte differentiation’, ‘leukocyte proliferation’ and ‘positive regulation of leukocyte-mediated immunity’, and was positively correlated with CD11b, CD14, CD45, CD163 and IL17A. Furthermore, DEFB4A expression was significantly upregulated in patients with large tumors, advanced cancer stage, lymph node metastasis and liver metastasis. Survival analysis revealed that DEFB4A upregulation was associated with poor prognosis. DEFB4A gene knockdown experiments demonstrated that DEF4BA promotes cell migration. These results indicated that DEFB4A potentially promotes tumor growth by regulating immunosuppressive activity and provided novel insights into the diagnosis and treatment of CRC.

Identification of Potential mRNA Biomarkers in Milk Small Extracellular Vesicles of Enzootic Bovine Leukosis Cattle

“…These mRNAs have been reported to be involved in various cancers in humans ( Table S2 ). CXCL8 and LAPTM5 proteins have been reported to promote cell activity [ 38 , 39 ], TMEM156 and LGALS1 proteins enhance cell invasion [ 40 , 41 ], VIM and LGALS1 proteins induce cell migration [ 40 , 42 ], FABP5 and SRGN proteins activate cancer metastasis [ 43 , 44 ], and the DEFB4A protein regulates immunity [ 45 ] in human cancers. Since EBL is a blood cancer and metastatic disease in cattle, these eight mRNAs may reflect the general condition during the onset of EBL, such as cell invasion and migration of tumor cells, and these eight mRNAs could be present in higher amounts in sEVs of EBL cattle than in those of uninfected cattle.…”

“…The following supporting information can be downloaded at: , Table S1: Oligonucleotide primers used for qPCR [ 55 , 56 ]; Table S2: Reports on mRNA functions in human cancer [ 41 , 45 , 57 , 58 , 59 , 60 , 61 , 62 ]; Figure S1: Correlation between BLV proviral load and amounts of mRNAs for biomarker candidates using milk small extracellular vesicles (sEVs); Figure S2: Correlation between total LDH (IU/l) and amounts of mRNAs for biomarker candidates using milk small extracellular vesicles (sEVs); Figure S3: Correlation between LDH 2+3 % and amounts of mRNAs for biomarker candidates using milk small extracellular vesicles (sEVs); Figure S4: Correlation between age and amounts of mRNAs for biomarker candidates using milk small extracellular vesicles (sEVs); Figure S5: Correlation between WBCs and amounts of mRNAs for biomarker candidates using milk small extracellular vesicles (sEVs); Figure S6: Correlation between lymphocyte and amounts of mRNAs for biomarker candidates using milk small extracellular vesicles (sEVs).…”

Orthodenticle homeobox OTX1 is a potential prognostic biomarker for bladder cancer

“…Total RNA (1 µg) extracted from cells were reversely transcribed into cDNA, and then real time qPCR was carried out according to the protocol of FastKing One Step RT-qPCR Kit (SYBR) (Tiangen, Beijing, China). Gene expression was normalized to that of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and quantified using the 2 −ΔΔCq method [ 34 ], and the primers are presented as following: OTX1 forward, 5′-CAGTGCTAATGCTTGCTC-3′ and reverse, 5′-TTGCTGTGTGCTAACGTC-3′; and GAPDH forward, 5′-GATCGTTCGAGACTCTTCC-3′ and reverse, 5′-CCTTAGCTGATGCAGCTG-3′ [ 35 ].…”

“…Gene expression was normalized to that of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and quantified using the 2 −ΔΔCq method [34], and the primers are presented as following: OTX1 forward, 5′-CAGTGCTAATGCTTGCTC-3′ and reverse, 5′-TTGCTGTGTGCTAACGTC-3′; and GAPDH forward, 5′-GATCGTTCGAGACTCTTCC-3′ and reverse, 5′-CCTTAGCTGATGCAGCTG-3′ [35].…”

Colorectal liver metastasis: molecular mechanism and interventional therapy

“… 202 The expression of defensin β 4 A ( DEFB4A ) was significantly upregulated and experimentally proved that DEFB4A gene knockdown proved that DEF4BA promoted cell migration. 203 Sialyltransferase ST6GAL1 can increase the stability of ICAM-1 through sialylation, thereby inhibiting the transfer characteristics of CRC. 204 …”