Increased expression of Fibrinogen-Like Protein 2 is associated with poor prognosis in patients with clear cell renal cell carcinoma

Abstract

Fibrinogen-like protein 2 (FGL2) is highly expressed in various tumour tissues and plays a vital role in tumour initiation and progression. This study evaluated the clinical significance of FGL2 in patients with clear cell renal cell carcinoma (ccRCC). FGL2 expression in fresh and 170 archived paraffin-embedded ccRCC tissues was measured by quantitative RT-PCR, western blotting, and immunohistochemitry. FGL2 expression was significantly upregulated in ccRCC. Statistical analyses by using Kaplan–Meier method showed that high FGL2 expression was associated with poor overall survival (OS) and recurrence-free survival (RFS) of patients with ccRCC. Multivariate analyses indicated that FGL2 was as an independent prognostic factor of survivaland that tumoural FGL2 levels could significantly predict the prognosis of patients with early-stage ccRCC. Nomogram systems, which integrated FGL2 expression and other clinical parameters, were established and were found to be better than TNM staging in predicting the OS and RFS of patients with ccRCC. FGL2 silencing led to a significant reduction in cells viability and increase in cells apoptosis, accompanied with a reduced ERK1/2 and p38 MAPK activation, in ccRCC cells. Thus, our results suggest that high FGL2 expression is a novel, independent, and an adverse prognostic factor of clinical outcomes in patients with ccRCC.

HVEM has a broader expression than PD-L1 and constitutes a negative prognostic marker and potential treatment target for melanoma

“…11 High levels of HVEM expression in human esophageal squamous cell carcinoma are associated with significantly lower survival rates. 12 Similar results have been obtained in colorectal cancer, 13 hepatocellular carcinoma, 14 breast cancer, 15 ovarian serous adenocarcinoma, 16 clear renal cell carcinoma 17 and glioblastoma 18 . However, the problem is more complex, since high levels of HVEM expression were associated with improved cancer-specific survival in other tumor like pancreatic, ampullary, 19 and bladder cancer.…”

Soluble fibrinogen-like protein 2 levels in patients with hepatitis B virus-related liver diseases

“…Quantification of cDNA was performed by quantitative real-time PCR with GAPDH (glyceraldehyde-3-phosphate dehydrogenase) as a reference gene. Primer sequences were FGL2_F: 5′-AGG CAG AAA CGG ACT GTT GT-3′ and FGL2_R: 5’-CCA GGC GAC CAT GAA GTA CA-3′, GAPDH_F: 5’-TGC ACC ACC AAC TGC TTA GC-3′ and GAPDH_R: 5’-GGC ATG GAC TGT GGT CAT GAG-3′ [ 25 ]. In brief: real-time PCR amplification was carried out in a reaction volume of 25 μl containing 12.5 μl 2X SYBR Green PCR master mix (Bioline, Luckenwalde, Germany), 0.5 μM specific primer pairs for target gene or reference gene, 5 ng cDNA and RNase-free water up to 25 μl of reaction volume.…”

Profiles of overall survival-related gene expression-based risk signature and their prognostic implications in clear cell renal cell carcinoma

“…The predictive performance of our nomogram was compared with several reported prognostic tools, which were retrieved from PubMed database using ‘ (overall survival) AND (((c-index) AND signature) AND ((((clear cell renal cell carcinoma) OR renal clear cell carcinoma) OR clear cell carcinoma) OR KIRC)) ’ as search terms. As presented in Table 4 , clinical features such as TNM stage [ 12 ], Fuhrman grade [ 12 ], and the UISS risk model [ 24 ] alone seemed to be less competitive in terms of discrimination (c-indices were 0.65, 0.61, and 0.72, respectively). Similarly, using only gene signature such as the ClearCode34, a 34-gene signature model, was hardly satisfying when predicting OS in stage IV ccRCC patients [ 25 ].…”