RESUMO
BACKGROUND: The expression of the L-type amino acid transporter 1 (LAT1) plays a significant role in tumor progression. However, it remains unclear whether high LAT1 expression correlates with poor prognosis of solid tumor patients. Here, we conducted a meta-analysis to assess the potential of LAT1 in predicting the prognosis of tumor patients. METHODS AND FINDINGS: A total of 4,579 cases were analyzed from 35 qualified studies. In patients with solid tumors, elevated expression of LAT1 is associated with poor prognosis (overall survival [OS]: pooled hazard ratio (HR) = 1.848, 95% confidence interval (CI) = 1.620-2.108, P < 0.001; disease free survival [DFS]: pooled HR = 1.923, 95% CI = 1.585-2.333, P < 0.001; progression free survival [PFS]: pooled HR = 1.345, 95% CI = 1.133-1.597, P = 0.001). Furthermore, in subgroup analysis, we found an association between high LAT1 expression and poor OS in non-small cell lung cancer (HR = 1.554, 95% CI = 1.345-1.794, P < 0.001), pancreatic cancer (HR = 2.052, 95% CI = 1.613-2.724, P < 0.001) and biliary tract cancer (HR = 2.253, 95% CI = 1.562-3.227, P < 0.001). CONCLUSION: The results of this meta-analysis indicate the reliability and potential of using LAT1 expression as a predictive biomarker in solid cancers prior to treatment. However, further studies with larger sample sizes would be beneficial for fully evaluating the predictive value of LAT1 expression for clinical applications.
Assuntos
Transportador 1 de Aminoácidos Neutros Grandes/análise , Neoplasias/diagnóstico , Neoplasias do Sistema Biliar/diagnóstico , Biomarcadores Tumorais/análise , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Prognóstico , Análise de SobrevidaRESUMO
Background: Albumin-to-globulin ratio (AGR) and the prognostic nutrition index (PNI) are used to assess the nutritional status and severity of disease for a cancer patient. However, the clinical significance of combining these two predictors in gastric cancer (GC) remains unclear. This study evaluated the prognostic value of pretreatment serum AGR and the PNI for GC.Methods: A total of 273 patients with GC, diagnosed between January 2010 and January 2014, were enrolled. The association of AGR, PNI with clinicopathological characters and prognosis were assessed by Cox regression and Kaplan-Meier methods.Results: Both low AGR group and low PNI group had poor overall survival (OS) and progression-free survival (PFS) (all p < 0.001), while patients with low AGR and PNI had the lowest OS rate. Multivariate analyses revealed that AGR (for OS HR = 0.657, 95%CI: 0.449-0.962, p = 0.031; for PFS HR = 0.684, 95%CI: 0.528-0.895, p = 0.035) was an independent prognostic factor for OS and PFS in patients with GC, and PNI was verified as a predictor for OS (HR = 0.782, 95%CI: 0.503 -0.997, p = 0.048).Conclusions: Low level of pretreatment AGR and PNI may be independent prognostic factors for patients with GC, and patients with both factors indicated the worst OS.
Assuntos
Globulinas/análise , Estado Nutricional , Albumina Sérica/análise , Neoplasias Gástricas/mortalidade , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação Nutricional , Prognóstico , Estudos Prospectivos , Neoplasias Gástricas/sangue , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologiaRESUMO
As the first biochemical step of olfactory reception and recognition, odorant binding proteins (OBPs) have been demonstrated to be essential. Considering functional diversities of OBPs within a single species, we here extended the characterization of two other OBPs from Spodoptera exigua, belonging to insect Classic OBPs. With a combination of transcriptome and Rapid Amplification of cDNA End (RACE) approaches, two OBP genes in S. exigua were identified, namely SexiOBP1 and OBP7. Expression pattern analysis revealed that both of them exhibited a distinct expression pattern, where OBP1 was broadly and highly expressed in several tissues including antennae of adults whereas OBP7 was abundant only in the antennae of both sexes, strongly indicative of olfactory roles. Further, binding assays showed that the two SexiOBPs shared a common odorant-response spectrum with considerable affinities to host odorants of acetophenone, farnesol and ß-ionone (Ki<20µM). Specially, OBP1 could strongly bind an insect attractant ß-caryophyllene (Ki=2.76µM) released by maize. Intriguingly, the major sex pheromone of S. exigua, Z9,E12-14:Ac, was the best ligand for OBP7 with Ki value of 7.58µM. Ligand structural analysis revealed that the two SexiOBPs were capable of accommodating different types of ligands in shape and size, possibly implying the plasticity of binding pockets. Ultimately, comparison of binding properties among 10 SexiOBPs including the two OBPs in this study implied a cross-talk in functions, i.e. different OBPs are also suitable to accept some common odorants except for unique ligands. Taken together, this study has provided evidence for their involvements in seeking and orientation of host plants, and meanwhile indicates functional conservation and differences between OBP1 and OBP7 from S. xigua.
Assuntos
Receptores Odorantes/metabolismo , Spodoptera/metabolismo , Animais , Clonagem Molecular , Eletroforese em Gel de Poliacrilamida , Feminino , Regulação da Expressão Gênica , Masculino , Reação em Cadeia da Polimerase em Tempo Real , Receptores Odorantes/genéticaRESUMO
The general pathway of biosynthesis and degradation for Type-I sex pheromones in moths is well established, but some genes involved in this pathway remain to be characterized. The purple stem borer, Sesamia inferens, employs a pheromone blend containing components with three different terminal functional groups (Z11-16:OAc, Z11-16:OH, and Z11-16:Ald) of Type-I sex pheromones. Thus, it provides a good model to study the diversity of genes involved in pheromone biosynthesis and degradation pathways. By analyzing previously obtained transcriptomic data of the sex pheromone glands and antennae, we identified 73 novel genes that are possibly related to pheromone biosynthesis (46 genes) or degradation (27 genes). Gene expression patterns and phylogenetic analysis revealed that one desaturase (SinfDes4), one fatty acid reductase (SinfFAR2), and one fatty acid xtransport protein (SinfFATP1) genes were predominantly expressed in pheromone glands, and clustered with genes involved in pheromone synthesis in other moth species. Ten genes including five carboxylesterases (SinfCXE10, 13, 14, 18, and 20), three aldehyde oxidases (SinfAOX1, 2 and 3), and two alcohol dehydrogenases (SinfAD1 and 3) were expressed specifically or predominantly in antennae, and could be candidate genes involved in pheromone degradation. SinfAD1 and 3 are the first reported alcohol dehydrogenase genes with antennae-biased expression. Based on these results we propose a pathway involving these potential enzyme-encoding gene candidates in sex pheromone biosynthesis and degradation in S. inferens. This study provides robust background information for further elucidation of the genetic basis of sex pheromone biosynthesis and degradation, and ultimately provides potential targets to disrupt sexual communication in S. inferens for control purposes.