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This study aimed to identify the key cell types and their interactions in gynecological oncology of breast cancer, cervical cancer, and ovarian cancer. Single-cell RNA sequencing was performed on tumor samples of gynecological oncology from the GEO database. Cell types were identified using SingleR and cell composition was analyzed to understand the tumor microenvironment (TME). CellChat was used to analyze cell interactions, and pseudotemporal analysis was conducted on cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs) to understand their differentiation status. Four CAF subtypes were identified: iCAF, myCAF, proCAF, and matCAF. The iCAF subpopulation secreted COL1A1 and promoted tumor cell migration, while myCAF was involved in angiogenesis. The matCAF subpopulation was present throughout tumor development. TAMs were found to promote angiogenesis through the VEGFA_VEGFR2 signaling pathway. CAFs and TAMs play pivotal roles in tumor progression through their interactions and signaling pathways.

Cervical cancer (CC) is a prevalent gynecological cancer worldwide that significantly impacts the quality of life and the physical and mental well-being of women. However, there have been limited studies utilizing Mendelian randomization (MR) analysis to investigate the connection between immune cells and CC. This study is to investigate the causal effects of immune traits on CC and non-neoplastic conditions of the cervix. The GWAS data for 731 immunophenotypes and six GWAS data for CC from the FinnGen database were downloaded. Subsequently, a two-sample MR analysis was conducted using the MR Egger, Weighted median, Inverse variance weighted (IVW), Simple mode, and Weighted mode methods. Our study has identified the potential causal effects of immune traits on inflammatory diseases of the cervix, other noninflammatory disorders of the cervix uteri, carcinoma in situ of cervix uteri, adenocarcinomas of cervix, squamous cell neoplasms and carcinoma of cervix, as well as malignant neoplasm of the cervix uteri, with the respective numbers being 8, 6, 11, 8, 23, and 12, respectively. A strong correlation between classic monocytes and various cervical diseases was revealed. Furthermore, we discovered that B cells expressing BAFF-R have the ability to impede the advancement of malignant CC, specifically squamous cell neoplasms and carcinoma of cervix. Our study has demonstrated a significant association between immune traits and both CC and non-neoplastic conditions of the cervix through two-sample Mendelian randomization, providing valuable insights for future clinical research.

Objective This study aims to elucidate the primary signaling communication among papillary craniopharyngioma (PCP) tumor cells. Methods Five samples of PCP were utilized for single-cell RNA sequencing. The most relevant ligand and receptor interactions among different cells were calculated using the CellChat package in R software. Bulk RNA sequencing of 11 tumor samples and five normal controls was used to investigate the pair interactions detected by single-cell RNA sequencing. Results Fibroblasts were not found in ACP, whereas they were detected in PCP. InferCNV revealed high CNV scores for the clusters of epithelial cells and fibroblasts using immune cells as a reference. Epithelial Mesenchymal Transition, Interferon Gamma Response, p53 Pathway, and Estrogen Response Early are pathways commonly shared by fibroblasts and epithelial cells, ranking high in priority. The Wnt signaling pathway and PI3K-Akt signaling pathway play a crucial role in facilitating communication between epithelial cells and fibroblasts. Neutrophils were recognized as the main receivers of incoming signals, with ANXA1-FPR1 and MIF-(CD74 + CXCR2) being identified as the primary signals transmitted from fibroblasts to neutrophils. Conclusion Through analyzing the communication of essential signaling pathways, ligands, and receptors among epithelial cells, fibroblasts, and neutrophils in PCP tumor tissues, we have identified certain molecules with promising prognostic and therapeutic potential.

Objective The study is to investigate differential signaling pathways within the tumor microenvironment across molecular subtypes of breast cancer (BC). Methods Single‐cell RNA (scRNA‐seq) sequencing data of BC samples were obtained from the Gene Expression Omnibus database. Cell types were identified using the SingleR package, in conjunction with the analysis of marker genes. Subsequently, Monocle was used for pseudotime analysis of epithelial cells, fibroblasts, and macrophages to characterize their differentiation states. CellChat was employed to study the ligand‐receptor interactions among various cell types across different BC molecular subtypes. In addition, we used common bulk RNA sequencing data from The Cancer Genome Atlas to investigate the correlation between key signaling pathway factors identified by scRNA‐seq and clinical outcomes. Results Inference of copy number variation analysis using T cells revealed significantly elevated copy number variation scores in epithelial cells and fibroblasts. In the communication between epithelial cells and fibroblasts, the ANGPTL pathway is critical in estrogen receptor‐positive breast cancer (ER+BC), while the PTN pathway plays a key role in both ER+BC and human epidermal growth factor receptor 2‐positive breast cancer (HER2+BC), and the GAS pathway is associated with poor prognosis in triple‐negative breast cancer (TNBC). In the interaction between fibroblasts and macrophages, the macrophage subpopulation supporting tumor angiogenesis exhibits significant activity in ER+BC, with the associated SPP1 and GRN pathways strongly influencing tumor progression. The SEMA3 pathway mainly acts through dividing tumor‐associated fibroblast clusters across all BC subtypes. When exploring the role of lymphocytes, the PTN pathway also plays a role in HER2+BC, while in TNBC, CXCL and CD70 pathways are significantly involved in immune response modulation. Conclusion Our comprehensive analysis of cell–cell communication networks among epithelial cells, fibroblasts, macrophages, and lymphocytes across BC subtypes focuses on ligand‐receptor interactions. This study revealed that certain molecules within these networks exhibit significant prognostic value and therapeutic promise. The figure shows single‐cell datasets of breast cancer collected from the GEO database, including estrogen receptor‐positive breast cancer, HER2‐positive breast cancer, and triple‐negative breast cancer. These datasets are used to analyze differences among breast cancer subtypes by studying the interactions among epithelial cells, fibroblasts, macrophages, and lymphocytes.

Lung cancer, particularly the non-small cell lung cancer (NSCLC) subtypes lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD), exhibits high heterogeneity and high mortality. This study aimed to explore their tumor microenvironment (TME) features, cellular interactions, and potential therapeutic targets. Using scRNA-seq datasets (GSE200972, GSE117570, and GSE127465) and TCGA bulk RNA-seq data, we performed cell clustering, pseudotime trajectory, cell-cell communication, and survival analyses. Batch correction and quality control were applied first, followed by cell type annotation with SingleR, copy number variation inference with InferCNV, and intercellular signaling investigation with CellChat. Four epithelial signatures (S1-S4) with distinct gene expression profiles were identified, with S3 specific to LUSC and correlated with high malignancy. Pseudotime analysis revealed distinct differentiation trajectories: S2→S1→S3/S4 in LUSC and S4→S1→S2 in LUAD. In LUSC, S3 interacted with macrophages via the and ligand-receptor pairs, involving the PI3K-Akt pathways; in LUAD, S4 communicated with neutrophils through , linked to interferon-related pathways. Macrophages played a central role in the TME, with as a key ligand-receptor pair in LUSC and in LUAD. Additionally, and expression correlated with prognosis in LUSC and LUAD, respectively. This study highlights subtype-specific epithelial signatures, identifies key signaling pathways (e.g., ), and pinpoints candidate therapeutic targets ( , ). These discoveries shed new light on the distinct pathogenic mechanisms of LUSC and LUAD and provide actionable insights to facilitate the clinical translation of subtype-specific personalized immunotherapies.

This study presents two Chinese siblings with a rare neurodevelopmental disorder (NDD) caused by biallelic INTS1 mutations and investigates the clinical features of this disease by means of in silico analysis. Two siblings, an 11-year-old brother and a 5-year-old sister, visited our hospital due to physical retardation and profound intellectual disability. Whole-exome sequencing (WES) was performed for the girl, and Sanger sequencing was used to validate the identified variants. Phenotype correlation analysis and in silico genetic interaction network analysis were performed to investigate genes that could lead to diseases similar to the rare disease in the patients. Growth retardation, distinct intellectual disability, hypertelorism, mild cataract, uneven teeth, abnormal palmar and plantar creases, and dubious genitalia were noted in the sister. No neurological features related to neuropathy were found. The brother showed features and growth delay similar to his sister. Heterozygous novel variants of c.1645A>G,p.Met549Val and c.5881C>T,p.Gln1961* in INTS1 were considered a candidate etiology. Sanger sequencing demonstrated that the variants were inherited from the grandfather and (maternal) grandmother. Phenotype correlation analysis revealed that CTDP1 mutation–induced congenital cataracts–facial dysmorphism–neuropathy (CCFDN) mostly overlapped with the performance of our patients. In silico analysis of the genetic interaction network showed that INTS1 is highly associated with INTS8 and CTDP1. Our study further validated that biallelic INTS1 mutations could bring about the onset of a novel neurodevelopmental disorder.

Neurodevelopmental delay accompanied unexplained dyspnea is a highly lethal disease in clinic. This study is to investigate the performance characteristics of trio whole exome sequencing (Trio-WES) in a pediatric setting by presenting our patient cohort and displaying the diagnostic yield. A total of 31 pediatric patients showing neurodevelopmental delay accompanied unexplained dyspnea were admitted to our hospital and referred for molecular genetic testing using Trio-WES. Eight genes namely MMACHC, G6PC, G6PT, ETFDH, OTC, NDUFAF5, SLC22A5 , and MAGEL2 were suspected to be responsible for the onset of the clinical symptoms and 6 variants were novel. Standard interpretation according to ACMG guideline showed that the variants were pathogenic. Finally, diagnosis of methylmalonic aciduria and homocystinuria, glycogen storage disease, ornithine transcarbamylase deficiency, glutaric acidemia II, mitochondrial complex 1 deficiency, carnitine deficiency, and Schaaf-Yang syndrome was made in 12 out of the 31 patients. Trio-WES is an effective means for molecular diagnosis of infantile neurodevelopmental delay accompanied unexplained dyspnea. As for molecular etiology identification, when routine potential monogenetic inheritance patterns including de novo , autosomal recessive, autosomal dominant, and X-linked recessive inheritance analysis is negative, physicians should take into account imprinted genes.

This study investigated the clinical and genetic characteristics of developmental disorders (DDs) in children attending a rehabilitation department. A total of 94 children with suspected rare and undiagnosed DDs were included in this study. All patients were subjected to next-generation sequencing by means of proband single whole-exome sequencing (Pro-WES) or trio whole-exome sequencing (Trio-WES). To investigate the copy number variations (CNVs), 63 patients were subjected to the trio strategy, and 17 cases were subjected to the proband single strategy. The patients developed early and suffered from severe symptoms. WES reached a high diagnostic rate (48.7%, 46/94), and de novo (48.3%, 28/58) was the main pathogenic form. Most identified single-nucleotide variations (SNVs)/small insertions and deletions (indels) were found only in one patient. The number of uncertain significant locus in the patients taking Trio-WES was significantly lower than that in patients taking Pro-WES (2.1% vs 2.8%). Compared with hereditary mutations passed from parents, pathogenicity was more obvious in de novo mutations. The diagnostic rate of WES accompanied by CNVseq (57.5%, 46/80) was significantly higher (p = 0.016) than WES alone. Next-generation sequencing exhibited a satisfactory diagnostic rate for DDs patients in the rehabilitation department. Compared with the proband-only model, the family trio strategy should be employed more frequently because it can reduce the number of uncertain significant sites and help to identify de novo pathogenic mutations.

Herein, we present a Chinese infant with an early-onset intellectual developmental disorder with cardiac arrhythmia syndrome. A 6-month-old boy visited our hospital because of convulsions and paroxysmal cyanosis for 1 day. Mental development analysis showed that the patient had a neurodevelopmental delay. Frequent seizures occurred, and ECG monitoring demonstrated severe cardiac arrhythmia. Whole-exome sequencing showed that the infant had two compound heterozygous variants, NM_016194:c.458G>A/p.Cys153Tyr and NM_016194:c.1032C>A/p.Tyr344*, in GNB5. The first variant was inherited from his mother, while the other one was a de novo variant. Haplotype analysis indicated that the de novo variant was located in the paternal chromosome. Structural modeling indicated that both mutations could influence the interaction of GNB5 with its binding protein. Our study expanded the known genetic and phenotypic spectrum of GNB5-associated diseases, by presenting a Chinese male infant with IDDCA.

This study is to present two Chinese siblings who were diagnosed with congenital disorders of glycosylation (CDG) IIb because of mannosyl-oligosaccharide glucosidase (MOGS) deficiency. The siblings visited our hospital due to \"pulmonary infection\". Facial dysmorphism including long eyelashes, blepharophimosis, depressed nasal bridge, and high palate was noted. Head MRI of the elder sister showed increased signals on T1W1, bilateral frontal gyrus stenosis, and thin corpus callosum. Both cases presented progressive hepatomegaly and elevated hepatic enzymes. Low immunoglobulin was discovered in the siblings. Compound heterozygous variants of NM_006302:c.1239_1267dup,p.Asp414Leufs*17, c.544 G > A,p.Gly182Arg, and c.1698C > A,p.Asp566Glu in MOGS were identified. Structural modeling demonstrated that the mutations were pathogenic to MOGS. Our study enriched the genetic and phenotypic spectrum of MOGS-CDG, and for children with facial dysmorphism, postnatal dyspnea, seizures, motor developmental delay, hypotonia, and immunological or gastrointestinal dysfunction, this disease should be highly suspected.