High expression levels of DEF6 predicts a poor prognosis for patients with clear cell renal cell carcinoma

Abstract

Clear cell renal cell carcinoma (ccRCC) is one of the most common types of malignant tumors and early detection contributes to a better prognosis. Finding new biomarkers for the diagnosis or treatment remains meaningful. DEF6 guanine nucleotide exchange factor (DEF6) is upregulated in ccRCC compared to normal controls, but the relationship between DEF6 expression and prognosis in ccRCC is unclear. Moreover, the potential biological functions of DEF6 in ccRCC remains unclear. In the present study, the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), TISIDB and the clinical database of the Peking University First Hospital were used to analyze DEF6 expression in ccRCC. Immunohistochemistry (IHC), western blotting and reverse transcription-quantitative PCR were used to examine the DEF6 protein and mRNA expression levels in cell lines and clinical samples. Subsequently, the Kaplan-Meier method and Cox regression analyses were used to determine the impact of DEF6 expression on the overall survival of patients alongside other clinical variables in both the TCGA database and the present clinical database. The results showed that both DEF6 mRNA and protein expression levels were upregulated in ccRCC compared to normal controls. The Kaplan-Meier survival analysis showed that patients with high DEF6 expression had poor prognoses from both the TCGA database and the present clinical database. Univariate survival analysis and multivariate survival analysis revealed that DEF6 could be an independent prognostic factor for ccRCC. Additionally, bioinformatics analysis indicated that differentially expressed genes related to DEF6 expression influenced ccRCC by regulating the tumor immune microenvironment. In conclusion, overexpression of DEF6 is significantly correlated with a poor prognosis for patients with ccRCC and DEF6 may influence the biological processes involved with ccRCC by regulating the immune microenvironment.

Identification of IL20RB as a Novel Prognostic and Therapeutic Biomarker in Clear Cell Renal Cell Carcinoma

“…FGL1, fibrinogen-like protein 1, which is known as a novel potential immune checkpoint target [ 58 ], was recognized to be upregulated in tumor tissues and plasma specimens of ccRCC patients, and high FGL1 expression predicted a poor prognosis. In fact, there are many genes that have been identified as potential biomarkers in ccRCC, such as ZNF433 [ 59 ], AQP9 [ 60 ], SPINK13 [ 61 ], and DEF6 [ 62 ]. These works are different from each other for their interested and focused genes vary, but all genes identified are treasures for they have enhanced our understanding of ccRCC.…”

Expression of PSTPIP1 in kidney renal clear cell carcinoma and its prognostic value

“…CORO1A, a member of the type coronin subfamily, participates in the regulation of actin cytoskeleton disassembly by targeting Co lin and Arp2/3. DEF6 is highly expressed in T and B cells and regulates various immune-related processes, such as the activation of CD4+ T cells and the differentiation of T helper cells (Zhu ZP et al 2020). More importantly, DEF6 has been identi ed as an independent factor involved in KIRC progression (Zhu ZP et al 2020).…”

“…DEF6 is highly expressed in T and B cells and regulates various immune-related processes, such as the activation of CD4+ T cells and the differentiation of T helper cells (Zhu ZP et al 2020). More importantly, DEF6 has been identi ed as an independent factor involved in KIRC progression (Zhu ZP et al 2020). All three genes are involved in cell movement, adhesion, and activation.…”

DEF6 has potential to be a biomarker for cancer prognosis: A pan-cancer analysis

“…In malignant tumors, DEF6 appears to be associated with a worse prognosis. In clear cell renal cell carcinoma, a high level of expression of DEF6 predicts poor prognosis ( 7 ); in human osteosarcoma, a high level of expression of DEF6 is associated with metastasis and poor prognosis ( 8 ); in ovarian carcinoma, a high level of expression of DEF6 is associated with poor prognosis ( 9 ). Overall, a high level of expression of DEF6 seems to be strongly associated with poor prognosis in patients, and studies in cancer are very limited.…”