All 4 patients with MAGE-A1-positive GC showed progressive disease, whereas MAGE-A1 expression was not detected in any of the 23 patients showing partial response (P=0.0302).
Two of 7 (29%) mut+ developed progressive disease and died with a median follow-up time of 22 months; while 13/18 (72%) mut- developed progressive disease and 10/18 (56%) died with median TTP of 12 months and median survival of 14 months.
Our results indicate that the hypermethylation of ZAR1 regions is extremely frequent in neuroblastomas and correlates with established markers of progressive disease and outcome.
A high expression of CD49d (>30%) was found in 142/415 (34%) patients and was associated with progressive disease (advanced clinical stage, high serum lactate dehydrogenase or β2 -microglobulin levels; all p < 0·05) and aggressive disease biology (increased ZAP70 or CD38, unmutated IGHV, trisomy 12, mutations of NOTCH1 and SF3B1; all P < 0·05).
Furthermore, c-Cbl was significantly hypophosphorylated in progressive disease, so that hypophosphorylated form of c-Cbl (c-Cbl.P) along with ZAP-70, set a cutoff ratio distributing patients with stable situation below 1, and those with progressive disease equal or above 1.
Among these ZAP-70 "outliers," those with Ig-mutated CLL had clinical features that are uncharacteristic of this CLL subtype: 2 required early treatment and 2 used a mutated VH3-21 gene, an IgVH gene that has been associated with progressive disease.
The results showed that XIAP positivity increased with progressive disease stage, although there was no significant correlation between XIAP positivity and combined N-RAS/B-RAF mutational status or clinical outcome.
For a number of genes, such as CXCL14, DKK1, DKK4, PEG10 and WIF1, quantitive RT-PCR was performed to verify up- or downregulation in progressive disease.
In contrast, VWF:Ag and the VWF:Ag/ADAMTS13:AC ratio were significantly lower in patients with SD, PR, and CR than in those with PD (<i>P <</i> 0.05 for both).
Plasma CD73, IL6, and VEGFD were identified as prognostic markers for progressive disease, and IL6 was associated with worse PFS confirming similar observations made in patients treated with other anti-angiogenic agents.
Clinically active MGN is associated with diminished expression of VEGF protein and mRNA, mainly in podocytes, and expression remains depressed in persistently active and/or progressive disease.
IHC and irGEP revealed that pretreatment immune activity-including expression of immune checkpoint molecules-for CUP was similar to that for ICI-responsive malignancies (antitumor immune cell signatures: CUP versus PD, P = 0.002-0.067; CUP versus non-PD, P = 0.591-0.999), although VEGFA expression was associated with suppression of antitumor immunity in CUP (P = 0.008, false discovery rate = 0.010).
Thus, in human DN, a decrease of VEGF-A, rather than the reported increase as described in some rodent models, may contribute to the progressive disease.
Patients with partial remission or stable disease had significantly lower levels of plasma VEGF than did patients with progressive disease, both at baseline (p=0.0341) and after 2 cycles of chemotherapy (p=0.0265).
When treated with VEGF-targeted therapy, 3 patients achieved a partial response, 7 patients had stable disease, and 5 patients developed progressive disease.
i) Serum VEGF levels were higher in patients with progressive disease than those in patients with a partial response or stable disease. ii) VEGF levels were higher in patients with alcoholic LC than those in patients with hepatitis C-related or hepatitis B-related LC. iii) VEGF levels were higher in stage IVB patients than those in patients with stage III or IVA disease. iv) VEGF levels were significantly higher in patients with giant or confluent multinodular tumors than those in patients with multiple discrete nodules. v) Serum VEGF levels were higher in patients with vascular invasion than in patients without vascular invasion.
Vascular endothelial growth factor (VEGF) blockade has been validated clinically as a treatment for human cancers, yet virtually all patients eventually develop progressive disease during therapy.