Prognostic nutritional index of early post-pembrolizumab therapy predicts long-term survival in patients with advanced urothelial carcinoma

Pembrolizumab has been widely used to treat advanced urothelial carcinoma that has progressed after first-line platinum-based chemotherapy. Because its clinical benefits are limited, biomarkers that can predict a good response to pembrolizumab are required. The prognostic nutritional index (PNI), calculated using the serum albumin level and peripheral lymphocyte count, has been evaluated as a predictive biomarker in cancer immunotherapy. The present study investigated the application of PNI as a predictive biomarker for pembrolizumab response in patients with advanced urothelial cancer. A retrospective study was conducted on 34 patients treated with pembrolizumab at Shiga University of Medical Science Hospital between January 2018 and July 2022. The posttreatment PNI (post-PNI) was calculated within 2 months of starting pembrolizumab. The present study investigated the association between post-PNI and objective response, overall survival (OS) and progression-free survival (PFS). The patient cohort was stratified into two categories, high and low post-PNI groups, with a cutoff value of post-PNI at 40. The higher post-PNI group demonstrated a better disease control rate than the lower post-PNI group (complete response + partial response + stable disease, 75 vs. 21%, P=0.004). Regarding median OS, the higher post-PNI group exhibited a significantly longer survival time than the lower post-PNI group (23.1 vs. 2.9 months, P<0.001). Similarly, the higher post-PNI group exhibited a significantly longer PFS than the lower post-PNI group (10.2 vs.1.9 months, P<0.001). Multivariate analysis showed that a higher post-PNI value was an independent predictor for OS (hazard ratio, 0.04; 95% confidence interval, 0.01-0.14; P<0.001) and PFS (hazard ratio, 0.12; 95% confidence interval, 0.04-0.35; P<0.001). The present study indicated that the post-PNI was a predictor of favorable clinical outcomes in patients treated with pembrolizumab for advanced urothelial carcinoma

Functional Divergence of G and Its Homologous Genes for Green Pigmentation in Soybean Seeds

The degradation of chlorophyll in mature soybean seeds is closely related to the development of their yellow color. In this study, we examined G, its homologue G-like (GL), and their mutant alleles and investigated the relationship between these genes and chlorophyll accumulation in the seed coats of mature seeds. Transient expression of G and GL proteins fused with green fluorescent protein revealed that both were localized in plastids. Overexpression of G resulted in the accumulation of chlorophyll in the seed coats and cotyledons of mature seeds, indicating that high expression levels of G result in chlorophyll accumulation that exceeds its metabolism in the seeds of yellow soybean. Analysis of near isogenic lines at the G locus demonstrated a significant difference in the chlorophyll content of the seed coats and cotyledons of mature seeds when G and mutant g alleles were expressed in the d(1)d(2) stay-green genetic background, indicating that the G protein might repress the SGR-independent degradation of chlorophyll. We examined the distribution of mutant alleles at the G and GL loci among cultivated and wild soybean germplasm. The g allele was widely distributed in cultivated soybean germplasm, except for green seed coat soybean lines, all of which contained the G allele. The gl alleles were much fewer in number than the g alleles and were mainly distributed in the genetic resources of cultivated soybean from Japan. None of the landraces and breeding lines investigated in this study were observed to contain both the g and gl alleles. Therefore, in conclusion, the mutation of the G locus alone is essential for establishing yellow soybeans, which are major current soybean breeding lines