Primary adult choroid plexus carcinomas: a single-center experience with a systematic review

ObjectivePrimary adult choroid plexus carcinomas (PACPCs) are extremely rare brain tumors. The existing literature primarily comprises case reports, which limits our understanding of this uncommon disease. This study aims to describe the clinical characteristics and prognosis of PACPCs, as well as to identify optimal treatment strategies.MethodsWe conducted a comprehensive analysis of clinical data from 7 patients with PACPCs who underwent surgical treatment at the Department of Neurosurgery, Beijing Tiantan Hospital, between March 2011 and March 2023. Additionally, a thorough search of the PubMed database was performed using the keywords “choroid plexus carcinoma” or “choroid plexus carcinomas” within the time frame of August 1975 to April 2023, which yielded a total of 28 identified cases. Subsequently, we evaluated risk factors for progression-free survival (PFS) and overall survival (OS) based on the pooled cases.ResultsThe pooled cohort, consisting of 7 cases from our institution and 28 cases from the literature, included 20 males and 15 females with a mean age of 44.3 ± 14.7 years (range: 21-73 years). Gross-total resection (GTR) and non-GTR were achieved in 22 (62.9%) and 13 (37.1%) patients, respectively. Radiotherapy and chemotherapy were administered to 29 (90.6%) and 13 (40.6%) patients, respectively. After a mean follow-up of 21.0 ± 26.7 months (range: 2-132 months), 18 patients were alive, and 11 patients had died. The multivariate Cox regression model demonstrated that non-GTR (HR 5.262, 95% CI 1.350-20.516, p=0.017) was a negative prognostic factor for OS. However, we did not find any risk factors for PFS.ConclusionComplete surgical resection should be considered as the primary treatment approach for this rare disease. Chemotherapy and radiotherapy appear to have limited effectiveness in treating this condition. Further research with large cohorts is needed to validate our conclusions

Clinical features and surgical outcomes of high grade pleomorphic xanthoastrocytomas: a single-center experience with a systematic review

PurposeHigh grade pleomorphic xanthoastrocytomas (HGPXAs) are very rare and their management and prognostic outcomes remain unclear. To better understand the disease, we aimed to evaluate the risk factors for progression-free survival (PFS) and overall survival (OS), and propose a treatment protocol based on cases from our institute and cases from the literature.MethodsThe authors reviewed the clinical data of 26 patients with HGPXAs who underwent surgical treatment in Department of Neurosurgery of Beijing Tiantan Hospital between August 2014 and September 2021. We also searched the PubMed database using the keywords “anaplastic” combined with “pleomorphic xanthoastrocytoma(s)” between January 1997 and October 2022. Risk factors for PFS and OS were evaluated in the pooled cases.ResultsThe authors’ cohort included 11 males and 15 females with a mean age of 36.7 ± 20.3 years (range: 5.5-71 years). Gross-total resection (GTR) and non-GTR were achieved in 17 (65.4%) and 9 (34.6%) patients, respectively. Radiotherapy and chemotherapy were administered to 22 and 20 patients, respectively. After a mean follow-up of 20.5 ± 21.2 months (range: 0.5-78.1 months), 7 patients suffered tumor recurrence and 6 patients died with a mean OS time of 19.4 ± 10.8 months (range: 8-36 months). In the literature between January 1997 and October 2022, 56 cases of HGPXAs were identified in 29 males and 27 females with a mean age of 29.6 ± 19.6 years (range; 4-74 years). Among them, 24 (44.4%) patients achieved GTR. Radiotherapy and chemotherapy was administered to 31 (62%) patients and 23 (46%) patients, respectively. After a median follow-up of 31.4 ± 35.3 months (range: 0.75-144 months), the mortality and recurrence rates were 32.5% (13/40) and 70% (28/40), respectively. Multivariate Cox regression model demonstrated that non-GTR (HR 0.380, 95% CI 0.174-0.831, p=0.015), age≥30 (HR 2.620, 95% CI 1.183-5.804, p=0.018), no RT (HR 0.334,95% CI 0.150-0.744, p=0.007) and no CT (HR 0.422, 95% CI 0.184-0.967, p=0.042) were negative prognostic factors for PFS. Non-GTR (HR 0.126, 95% CI 0.037-0.422, p=0.001), secondary HGPXAs (HR 7.567, 95% CI 2.221-25.781, p=0.001), age≥30 (HR 3.568, 95% CI 1.190-10.694, p=0.023) and no RT (HR 0.223,95% CI 0.073-0.681, p=0.008) were risk factors for OS.Conclusion:High grade pleomorphic xanthoastrocytomas are very rare brain tumors. Children and younger adults have better clinical outcome than elderly patients. Secondary HGPXAs had worse OS than primary HGPXAs. Complete surgical excision plus RT and CT is recommended for this entity. The frequency of BRAF mutations in HGPXAs is 47.5% (19/40) in this study, however, we do not find the connections between BRAF mutations and clinical outcomes. Future studies with larger cohorts are necessary to verify our findings

Genetic polymorphisms and phylogenetic characteristics of Tibeto-Burman-speaking Lahu population from southwest China based on 41 Y-STR loci

Background Male sex-linked Y-chromosome short tandem repeats (Y-STRs) have been widely used in forensic cases and population genetics research. At present, the forensic-related Y-STR data in the Chinese Lahu population are still poorly understood. Aim To enrich the available Y-STR data of this Chinese minority population and investigate its phylogenetic relationships with other reported populations. Subjects and methods The genetic polymorphisms of 41 Y-STR loci were analysed in 299 unrelated healthy Lahu male individuals from Southwest China. Phylogenetic analyses were performed by multidimensional scaling analysis and neighbor-joining phylogenetic tree construction. Results A total of 379 alleles were observed at the 41 Y-STR loci. The allele frequencies ranged from 0.0033 to 0.9666. The genetic diversity values ranged from 0.0653 to 0.9072. A total of 254 different haplotypes of the 41 Y-STR loci were observed in 299 individuals. The values of haplotype diversity, haplotype match probability, and discrimination capacity were 0.9987, 0.0047, and 0.8495, respectively. The phylogenetic analysis indicated that the Tibeto-Burman-speaking Lahu population showed a close genetic relationship with the Yunnan Yi population. Conclusions The haplotype data of the present study can enrich the forensic databases of this Chinese minority population and will be useful for population genetics and forensic DNA application

Classifying Breast Cancer Subtypes Using Multiple Kernel Learning Based on Omics Data

It is very significant to explore the intrinsic differences in breast cancer subtypes. These intrinsic differences are closely related to clinical diagnosis and designation of treatment plans. With the accumulation of biological and medicine datasets, there are many different omics data that can be viewed in different aspects. Combining these multiple omics data can improve the accuracy of prediction. Meanwhile; there are also many different databases available for us to download different types of omics data. In this article, we use estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) to define breast cancer subtypes and classify any two breast cancer subtypes using SMO-MKL algorithm. We collected mRNA data, methylation data and copy number variation (CNV) data from TCGA to classify breast cancer subtypes. Multiple Kernel Learning (MKL) is employed to use these omics data distinctly. The result of using three omics data with multiple kernels is better than that of using single omics data with multiple kernels. Furthermore; these significant genes and pathways discovered in the feature selection process are also analyzed. In experiments; the proposed method outperforms other state-of-the-art methods and has abundant biological interpretations

Large Scale Profiling of Protein Isoforms Using Label-Free Quantitative Proteomics Revealed the Regulation of Nonsense-Mediated Decay in Moso Bamboo (Phyllostachys edulis).

Moso bamboo is an important forest species with a variety of ecological, economic, and cultural values. However, the gene annotation information of moso bamboo is only based on the transcriptome sequencing, lacking the evidence of proteome. The lignification and fiber in moso bamboo leads to a difficulty in the extraction of protein using conventional methods, which seriously hinders research on the proteomics of moso bamboo. The purpose of this study is to establish efficient methods for extracting the total proteins from moso bamboo for following mass spectrometry-based quantitative proteome identification. Here, we have successfully established a set of efficient methods for extracting total proteins of moso bamboo followed by mass spectrometry-based label-free quantitative proteome identification, which further improved the protein annotation of moso bamboo genes. In this study, 10,376 predicted coding genes were confirmed by quantitative proteomics, accounting for 35.8% of all annotated protein-coding genes. Proteome analysis also revealed the protein-coding potential of 1015 predicted long noncoding RNA (lncRNA), accounting for 51.03% of annotated lncRNAs. Thus, mass spectrometry-based proteomics provides a reliable method for gene annotation. Especially, quantitative proteomics revealed the translation patterns of proteins in moso bamboo. In addition, the 3284 transcript isoforms from 2663 genes identified by Pacific BioSciences (PacBio) single-molecule real-time long-read isoform sequencing (Iso-Seq) was confirmed on the protein level by mass spectrometry. Furthermore, domain analysis of mass spectrometry-identified proteins encoded in the same genomic locus revealed variations in domain composition pointing towards a functional diversification of protein isoform. Finally, we found that part transcripts targeted by nonsense-mediated mRNA decay (NMD) could also be translated into proteins. In summary, proteomic analysis in this study improves the proteomics-assisted genome annotation of moso bamboo and is valuable to the large-scale research of functional genomics in moso bamboo. In summary, this study provided a theoretical basis and technical support for directional gene function analysis at the proteomics level in moso bamboo

LGR4 and LGR5 form distinct homodimers that only LGR4 complexes with RNF43/ZNRF3 to provide high affinity binding of R-spondin ligands

Abstract LGR4 and LGR5 are two homologous receptors that potentiate Wnt/β-catenin signaling in response to R-spondin (RSPO) ligands. The RSPO and LGR4 complex binds to and inhibits activities of two related E3 ubiquitin ligases, RNF43 and ZNRF3, and thus protects Wnt receptors from the E3 ligase-mediated degradation. The RSPO and LGR5 complex, however, does not interact with the E3 ligases, and the structural basis of this difference remained unknown. Here we examined the affinities of monovalent and bivalent RSPO ligands in binding to LGR4, RNF43/ZNRF3, and LGR5 in whole cells and found unique features among the receptors and E3 ligases. Monovalent RSPO2 furin domain had much lower affinity in binding to LGR4 or RNF43/ZNRF3 than the bivalent form. In contrast, monovalent and bivalent forms had nearly identical affinity in binding to LGR5. Co-expression of ZNRF3 with LGR4 led to much higher binding affinity of the monovalent form whereas co-expression of ZNRF3 with LGR5 had no effect on the affinity. These results suggest that LGR4 and RNF43/ZNRF3 form a 2:2 dimer that accommodates bivalent binding of RSPO whereas LGR5 forms a homodimer that does not. Structural models are proposed to illustrate how RSPOs bind to LGR4, RNF43/ZNRF3, and LGR5 in whole cells

Comparative Proteomics Combined with Morphophysiological Analysis Revealed Chilling Response Patterns in Two Contrasting Maize Genotypes

Maize yield is significantly influenced by low temperature, particularly chilling stress at the maize seedling stage. Various physiological approaches have been established to resist chilling stress; however, the detailed proteins change patterns underlying the maize chilling stress response at the seedling stage remain unknown, preventing the development of breeding-based methods to resist chilling stress in maize. Thus, we performed comprehensive physiological, comparative proteomics and specific phytohormone abscisic acid (ABA) assay on different maize inbred lines (tolerant-line KR701 and sensitive-line hei8834) at different seedling stages (the first leaf stage and third leaf stage) under chilling stress. The results revealed several signalling proteins and pathways in response to chilling stress at the maize seedling stage. Meanwhile, we found ABA pathway was important for chilling resistance of tolerant-line KR701 at the first leaf stage. Related chilling-responsive proteins were further catalogued and analysed, providing a resource for further investigation and maize breeding