Clinical features, MRI, molecular alternations, and prognosis of astrocytoma based on WHO 2021 classification of central nervous system tumors: A single-center retrospective study.

BACKGROUND: The diagnosis of glioma has advanced since the release of the WHO 2021 classification with more molecular alterations involved in the integrated diagnostic pathways. Our study aimed to present our experience with the clinical features and management of astrocytoma, IDH mutant based on the latest WHO classification. METHODS: Patients diagnosed with astrocytoma, IDH-mutant based on the WHO 5th edition classification of CNS tumors at our center from January 2009 to January 2022 were included. Patients were divided into WHO 2-3 grade group and WHO 4 grade group. Integrate diagnoses were retrospectively confirmed according to WHO 2016 and 2021 classification. Clinical and MRI characteristics were reviewed, and survival analysis was performed. RESULTS: A total of 60 patients were enrolled. 21.67% (13/60) of all patients changed tumor grade from WHO 4th edition classification to WHO 5th edition. Of these, 21.43% (6/28) of grade II astrocytoma and 58.33% (7/12) of grade III astrocytoma according to WHO 4th edition classification changed to grade 4 according to WHO 5th edition classification. Sex (p = 0.042), recurrent glioma (p = 0.006), and Ki-67 index (p < 0.001) of pathological examination were statistically different in the WHO grade 2-3 group (n = 27) and WHO grade 4 group (n = 33). CDK6 (p = 0.004), FGFR2 (p = 0.003), and MYC (p = 0.004) alterations showed an enrichment in the WHO grade 4 group. Patients with higher grade showed shorter mOS (mOS = 75.9 m, 53.6 m, 26.4 m for grade 2, 3, and 4, respectively, p = 0.01). CONCLUSIONS: Patients diagnosed as WHO grade 4 according to the 5th edition WHO classification based on molecular alterations are more likely to have poorer prognosis. Therefore, treatment should be tailored to their individual needs. Further research is needed for the management of IDH-mutant astrocytoma is needed in the future.

Mosaic distal 9p deletion or 46,XY,del(9)(p23)/46,XY at amniocentesis in a pregnancy associated with perinatal progressive decrease of the aneuploid cell line and a favorable fetal outcome.

OBJECTIVE: We present mosaic distal 9p deletion at prenatal diagnosis in a pregnancy associated with a favorable fetal outcome. CASE REPORT: A 34-year-old, primigravid woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 46,XY, del(9)(p23)[8]/46,XY[17]. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes showed 43% mosaicism for the 9p24.3p23 deletion. Prenatal ultrasound suspected hypospadias and echogenic bowel. At 23 weeks of gestation, she was referred for genetic counseling, and repeat amniocentesis revealed a karyotype of 46,XY,del(9)(p23)[10]/46,XY[10]. The parental karyotypes were normal. Molecular genetic analysis on uncultured amniocytes revealed no uniparental disomy (UPD) 9 by quantitative fluorescence polymerase chain reaction (QF-PCR) and arr 9p24.3p23 × 1.55 (40%-50% mosaicism) by aCGH. At 27 weeks of gestation, she underwent the third amniocentesis which revealed a karyotype of 46,XY,del(9)(p23)[6]/46,XY[14]. Simultaneous aCGH analysis on the DNA extracted from uncultured amniocytes revealed the result of arr 9p24.3p23 (35% mosaicism). Prenatal ultrasound was normal. She was advised to continue the pregnancy, and a 3020-g phenotypically normal male baby was delivered at 41 weeks of gestation. At birth, the karyotypes of cord blood, umbilical cord and placenta were 46,XY,del(9)(p23)[7]/46,XY[37], 46,XY,del(9)(p23)[17]/46,XY[23] and 46,XY in 40/40 cells, respectively. When follow-up at age three months, the neonate was normal in phenotype and development. The peripheral blood had a karyotype of 46,XY,del(9)(p23)[3]/46,XY[37], and interphase fluorescence in situ hybridization (FISH) analysis on buccal mucosal cells showed 13% (13/102 cells) mosaicism for the distal 9p deletion. CONCLUSION: Mosaic distal 9p deletion with a normal cell line at prenatal diagnosis can be associated with a favorable fetal outcome and perinatal progressive decrease of the aneuploid cell line.

Immune checkpoint inhibitors-induced diabetes mellitus (review).

Immune checkpoint inhibitors (ICIs) have become extensively utilized in the early-stage treatment of various cancers, offering additional therapeutic possibilities for patients with advanced cancer. However, certain patient populations are susceptible to experiencing toxic adverse effects from ICIs, such as thyrotoxicosis, rashes, among others. Specifically, ICIDM, induced by immune checkpoint inhibitors, exhibits characteristics similar to insulin-dependent diabetes mellitus (Type 1 Diabetes Mellitus, T1DM). ICIDM is characterized by a rapid onset and may coincide with severe ketoacidosis. Despite a favorable response to insulin therapy, patients typically require lifelong insulin dependence. After discussing the autoimmune adverse effects and the specifics of ICIs-induced diabetes mellitus (ICIDM), it is important to note that certain patient populations are particularly susceptible to experiencing toxic adverse effects from ICIs. Specifically, ICIDM, which is triggered by immune checkpoint inhibitors, mirrors the characteristics of insulin-dependent diabetes mellitus (Type 1 Diabetes Mellitus, T1DM). This article conducts an in-depth analysis of the literature to explore the pathogenesis, disease progression, and treatment strategies applicable to diabetes induced by immune checkpoint inhibitors (ICIDM).

The molecular signature and prognosis of glioma with preoperative intratumoral hemorrhage: a retrospective cohort analysis.

BACKGROUND: Intratumoral hemorrhage, though less common, could be the first clinical manifestation of glioma and is detectable via MRI; however, its exact impacts on patient outcomes remain unclear and controversial. The 2021 WHO CNS 5 classification emphasised genetic and molecular features, initiating the necessity to establish the correlation between hemorrhage and molecular alterations. This study aims to determine the prevalence of intratumoral hemorrhage in glioma subtypes and identify associated molecular and clinical characteristics to improve patient management. METHODS: Integrated clinical data and imaging studies of patients who underwent surgery at the Department of Neurosurgery at Peking Union Medical College Hospital from January 2011 to January 2022 with pathological confirmation of glioma were retrospectively reviewed. Patients were divided into hemorrhage and non-hemorrhage groups based on preoperative magnetic resonance imaging. A comparison and survival analysis were conducted with the two groups. In terms of subgroup analysis, we classified patients into astrocytoma, IDH-mutant; oligodendroglioma, IDH-mutant, 1p/19q-codeleted; glioblastoma, IDH-wildtype; pediatric-type gliomas; or circumscribed glioma using integrated histological and molecular characteristics, according to WHO CNS 5 classifications. RESULTS: 457 patients were enrolled in the analysis, including 67 (14.7%) patients with intratumoral hemorrhage. The hemorrhage group was significantly older and had worse preoperative Karnofsky performance scores. The hemorrhage group had a higher occurrence of neurological impairment and a higher Ki-67 index. Molecular analysis indicated that CDKN2B, KMT5B, and PIK3CA alteration occurred more in the hemorrhage group (CDKN2B, 84.4% vs. 62.2%, p = 0.029; KMT5B, 25.0% vs. 8.9%, p = 0.029; and PIK3CA, 81.3% vs. 58.5%, p = 0.029). Survival analysis showed significantly worse prognoses for the hemorrhage group (hemorrhage 18.4 months vs. non-hemorrhage 39.1 months, p = 0.01). In subgroup analysis, the multivariate analysis showed that intra-tumoral hemorrhage is an independent risk factor only in glioblastoma, IDH-wildtype (162 cases of 457 overall, HR = 1.72, p = 0.026), but not in other types of gliomas. The molecular alteration of CDK6 (hemorrhage group p = 0.004, non-hemorrhage group p < 0.001), EGFR (hemorrhage group p = 0.003, non-hemorrhage group p = 0.001), and FGFR2 (hemorrhage group p = 0.007, non-hemorrhage group p = 0.001) was associated with shorter overall survival time in both hemorrhage and non-hemorrhage groups. CONCLUSIONS: Glioma patients with preoperative intratumoral hemorrhage had unfavorable prognoses compared to their nonhemorrhage counterparts. CDKN2B, KMT5B, and PIK3CA alterations were associated with an increased occurrence of intratumoral hemorrhage, which might be future targets for further investigation of intratumoral hemorrhage.

Enhancing immunotherapy outcomes by targeted remodeling of the tumor microenvironment via combined cGAS-STING pathway strategies.

Immune checkpoint inhibitors (ICIs) represent a groundbreaking advance in the treatment of malignancies such as melanoma and non-small cell lung cancer, showcasing substantial therapeutic benefits. Nonetheless, the efficacy of ICIs is limited to a small subset of patients, primarily benefiting those with "hot" tumors characterized by significant immune infiltration. The challenge of converting "cold" tumors, which exhibit minimal immune activity, into "hot" tumors to enhance their responsiveness to ICIs is a critical and complex area of current research. Central to this endeavor is the activation of the cGAS-STING pathway, a pivotal nexus between innate and adaptive immunity. This pathway's activation promotes the production of type I interferon (IFN) and the recruitment of CD8+ T cells, thereby transforming the tumor microenvironment (TME) from "cold" to "hot". This review comprehensively explores the cGAS-STING pathway's role in reconditioning the TME, detailing the underlying mechanisms of innate and adaptive immunity and highlighting the contributions of various immune cells to tumor immunity. Furthermore, we delve into the latest clinical research on STING agonists and their potential in combination therapies, targeting this pathway. The discussion concludes with an examination of the challenges facing the advancement of promising STING agonists in clinical trials and the pressing issues within the cGAS-STING signaling pathway research.

Mosaic distal 10q deletion or 46,XY,del(10) (q26.13)/46,XY at amniocentesis and cordocentesis in a pregnancy associated with cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes, perinatal progressive decrease of the aneuploid cell line and a favorable fetal outcome.

OBJECTIVE: We present mosaic distal 10q deletion at prenatal diagnosis in a pregnancy associated with a favorable fetal outcome. CASE REPORT: A 40-year-old, gravida 2, para 0, woman underwent amniocentesis at 16 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 46,XY, del(10) (q26.13)[6]/46,XY[17]. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes showed 35% mosaicism for the 10q26.13q26.3 deletion. At 22 weeks of gestation, she underwent cordocentesis which revealed a karyotype of 46,XY,del(10) (q26.13)[16]/46,XY[24]. Prenatal ultrasound findings were normal. At 24 weeks of gestation, she was referred for genetic counseling, and repeat amniocentesis revealed a karyotype of 46,XY,del(10) (q26.13)[4]/46,XY[22]. The parental karyotypes were normal. Molecular genetic analysis on uncultured amniocytes revealed no uniparental disomy (UPD) 10 by quantitative fluorescence polymerase chain reaction (QF-PCR), arr 10q26.13q26.3 × 1.6 (40% mosaicism) by aCGH, and 29.8% (31/104 cells) mosaicism for the distal 10q deletion by interphase fluorescence in situ hybridization (FISH). The woman was advised to continue the pregnancy, and a phenotypically normal 2,900-g male baby was delivered at 39 weeks of gestation. The cord blood had a karyotype of 46,XY,del(10) (q26.13)[6]/46,XY[34], and both the umbilical cord and the placenta had the karyotype of 46,XY. When follow-up at age four months, the neonate was normal in phenotype and development. The peripheral blood had a karyotype of 46,XY,del(10) (q26.13)[5]/46,XY[35], and interphase FISH analysis on buccal mucosal cells showed 8% (8/102 cells) mosaicism for distal 10q deletion. CONCLUSION: Mosaic distal 10q deletion with a normal cell line at prenatal diagnosis can be associated with a favorable fetal outcome and perinatal progressive decrease of the aneuploid cell line.

Scalp Metastasis After Breast Cancer Surgery: A Case Report.

Breast cancer is one of the most common malignant tumors affecting women worldwide. Breast cancer is a complex disease characterized by abnormal growth of cells in the breast tissue. Metastasis, the spread of cancer cells from the primary tumor site to distant organs, is a major challenge in the management of breast cancer. Although metastasis to distant sites is a well-known feature of breast cancer, scalp involvement is relatively rare. The occurrence of scalp metastasis signifies an advanced stage of the disease. The 51-year-old female discovered a firm, painless mass in her right breast that had been there for two years. It had been pricking for a month, and the biopsy revealed that the mass was invasive carcinoma of the right breast. Imaging tests suggested that the tumor was malignant. Adjuvant endocrine therapy and postoperative adjuvant chemotherapy were administered following a modified radical resection for breast cancer. Eleven months later, radiation treatment and replace endocrine therapy was used. 32 months following surgery, a scalp tumor was discovered; a pathology biopsy verified the origin of the breast cancer; three months later, bone, brain, and visceral metastases were discovered. After that, she received oral capecitabine treatment and was admitted into the hospital for advanced rescue treatment. She is currently in the disease stability state, her disease is effectively managed, and no new metastatic lesions have been discovered.

Clinical roles of EGFR amplification in diffuse gliomas: a real-world study using the 2021 WHO classification of CNS tumors.

Background: The 2021 World Health Organization Classification of Central Nervous System Tumors updates glioma subtyping and grading system, and incorporates EGFR amplification (Amp) as one of diagnostic markers for glioblastoma (GBM). Purpose: This study aimed to describe the frequency, clinical value and molecular correlation of EGFR Amp in diffuse gliomas based on the latest classification. Methods: We reviewed glioma patients between 2011 and 2022 at our hospital, and included 187 adult glioma patients with available tumor tissue for detection of EGFR Amp and other 59 molecular markers of interest. Clinical, radiological and pathological data was analyzed based on the status of EGFR Amp in different glioma subtypes. Results: 163 gliomas were classified as adult-type diffuse gliomas, and the number of astrocytoma, oligodendroglioma and GBM was 41, 46, and 76. EGFR Amp was more common in IDH-wildtype diffuse gliomas (66.0%) and GBM (85.5%) than IDH-mutant diffuse gliomas (32.2%) and its subtypes (astrocytoma, 29.3%; oligodendroglioma, 34.8%). EGFR Amp did not stratify overall survival (OS) in IDH-mutant diffuse gliomas and astrocytoma, while was significantly associated with poorer OS in IDH-wildtype diffuse gliomas, histologic grade 2 and 3 IDH-wildtype diffuse astrocytic gliomas and GBM. Conclusion: Our study validated EGFR Amp as a diagnostic marker for GBM and still a useful predictor for shortened OS in this group.

Integrative proteomics and metabolomics data analysis exploring the mechanism of brain injury after cardiac surgery in chronic stress rats.

OBJECTIVE: Preoperative chronic stress (CS) is associated with postoperative brain injury in patients undergoing open heart cardiac surgery. This research is to explore the potential molecular biological mechanisms of brain damage following cardiac surgery in preoperative CS rats by the analyses combining proteomics and metabolomics. METHODS: We constructed the chronic unpredictable stress (CUS) and cardiac surgery models in adult rats. We proved the brain injury in CUS cardiac surgery rats by Hematoxylin-Eosin (H&E) staining, followed by separating the hippocampal tissue and investigating the potential mechanisms of brain injury by the methods of data-independent acquisition proteomics and untargeted metabolomics. RESULTS: The signaling pathways of glycoproteins and metabolism of amino acids were the main possible mechanisms of brain injury in CUS rats following cardiac surgery according to the proteomics and metabolomics. In addition, the pathways of animo acids metabolism such as the pathways of lysine degradation and ß-alanine metabolism may be the main mechanism of cardiac surgery related brain injury in preoperative CUS rats. CONCLUSIONS: The pathways of animo acids metabolism such as lysine degradation and ß-alanine metabolism may be the potential mechanisms of brain injury in CUS rats following cardiac surgery. We should focus on the varieties of bioproteins and metabolites in these pathways, and related changes in other signaling pathways induced by the two pathways.

A prognostic model for overall survival in recurrent glioma patients treated with bevacizumab-containing therapy.

Predictive markers and prognostic models are useful for the individualization of cancer treatment. In this study, we sought to identify clinical and molecular factors to predict overall survival in recurrent glioma patients receiving bevacizumab-containing regimens. A cohort of 102 patients was retrospectively collected from June 2011 to January 2022 at our institution. A nomogram was generated by Cox regression and feature selection algorithms based on 19 clinicopathological and 60 molecular variables. The model's performance was internally evaluated by bootstrapping in terms of discrimination and calibration. The median overall survival from the initiation of bevacizumab administration to death or last follow-up was 11.6 months (95% CI: 9.2-13.8 months) for all 102 patients, 10.2 months (95% CI: 6.4-13.3 months) for 66 patients with grade 4 tumors, and 13.8 months (lower limit of 95% CI: 11.5 months) for 36 patients with tumors of grade lower or not available. In the final model, a lower WHO 2021 grade (Grade lower or not available vs. Grade 4, HR: 0.398, 95% CI: 0.223-0.708, p = 0.00172), having received adjuvant radiochemotherapy (Yes vs. No, HR: 0.488, 95% CI: 0.268-0.888, p = 0.0189), and wildtype EGFR (Wildtype vs. Altered, HR: 0.193, 95% CI: 0.0506-0.733, p = 0.0157; Not available vs. Altered, HR: 0.386, 95% CI: 0.184-0.810, p = 0.0118) were significantly associated with longer overall survival in multivariate Cox regression. The overall concordance index was 0.652 (95% CI: 0.566-0.714), and the areas under the time-dependent curves for 6-, 12-, and 18-month overall survival were 0.677 (95% CI: 0.516-0.816), 0.654 (95% CI: 0.470-0.823), and 0.675 (95% CI: 0.491-0.860), respectively. A prognostic model for overall survival in recurrent glioma patients treated with bevacizumab-based therapy was established and internally validated. It could serve as a reference tool for clinicians to assess the extent the patients may benefit from bevacizumab and stratify their treatment response.

Molecular Determinants of Neurocognitive Deficits in Glioma: Based on 2021 WHO Classification.

Cognitive impairment is a common feature among patients with diffuse glioma. The objective of the study is to investigate the relationship between preoperative cognitive function and clinical as well as molecular factors, firstly based on the new 2021 World Health Organization's updated classification of central nervous system tumors. A total of 110 diffuse glioma patients enrolled underwent preoperative cognitive assessments using the Mini-Mental State Examination and Montreal Cognitive Assessment. Clinical information was collected from medical records, and gene sequencing was performed to analyze the 18 most influenced genes. The differences in cognitive function between patients with and without glioblastoma were compared under both the 2016 and 2021 WHO classification of tumors of the central nervous system to assess their effect of differentiation on cognition. The study found that age, tumor location, and glioblastoma had significant differences in cognitive function. Several genetic alterations were significantly correlated with cognition. Especially, IDH, CIC, and ATRX are positively correlated with several cognitive domains, while most other genes are negatively correlated. For most focused genes, patients with a low number of genetic alterations tended to have better cognitive function. Our study suggested that, in addition to clinical characteristics such as age, histological type, and tumor location, molecular characteristics play a crucial role in cognitive function. Further research into the mechanisms by which tumors affect brain function is expected to enhance the quality of life for glioma patients. This study highlights the importance of considering both clinical and molecular factors in the management of glioma patients to improve cognitive outcomes.

Analysis of clinical factors impacting recurrence in myxofibrosarcoma.

Myxofibrosarcoma (MFS) is a malignant fibroblastic/myofibroblastic neoplasm with a prominent myxoid area. It has the clinical features of frequent local recurrence (LR) and occasional distant metastasis. Robust epidemiological data on MFS in China are lacking. The aim of this retrospective analysis was to determine the natural history of MFS, identify prognostic factors for recurrence and describe the real-life outcomes of MFS. We reviewed 52 patients with primary MFS from the First Affiliated Hospital of Nanjing Medical University diagnosed between 2016 and 2020. All tumors were subjected to retrospective univariate analysis for prognostic factors of the disease, including tumor size, grade, location and sex; patient age; planned operation; surgical margin; and laboratory results. The significant factors identified by univariate analysis were subsequently analyzed via multivariate analysis. Overall survival (OS), post-treatment LR and metastatic-free survival were assessed as outcomes. The median age was 61 years (range, 13-93). Fourteen (26.92%) patients exhibited low grade disease, and 38 (73.08%) exhibited high grade disease. Among the 29 males, and 23 females, 15 (28.85%) had tumors in the trunk, 37 (71.15%) had tumors in the extremities, 26 had undergone planned surgery, and 26 had unexpected unplanned operation. The margin was negative in 39 (75%) patients and positive in 13 patients (25%). The serum creatine kinase (CK) concentration was high level in 33 (63.46%) patients and low level in 19 (36.54%) patients. The serum lactate dehydrogenase (LDH) levels were low in 23 (44.23%) patients and high in 29 (55.77%) patients. LR was observed in 25 patients (48.08%), and 4 patients developed metastasis. A worse LR rate was found for patients with a low CK level (84.21%) than for those with a high CK level (27.27%) at 5 years (p < 0.05). The LR rate of patients who underwent planned surgery was lower than that of patients who underwent unplanned surgery (p < 0.05). There were significantly more patients with positive margins than patients with negative margins (92.30%, and 33.33%, respectively; p < 0.05). Moreover, superficial tumors were also associated with greater recurrence rate (2/20 [10%]) than deep tumors, (23/32 [71.86%]) [p < 0.05]. The probability of LR in patients with MFS was significantly greater in association with unplanned operations, positive margins, low serum CK levels or superficial tumor depth. These data could help identify high-risk patients; thus, more careful follow-up should be performed for higher-risk patients. Diagnosis and treatment at qualified regular medical centers can reduce the local recurrence rate of MFS.

Changes in the fecal microbiota of breast cancer patients based on 16S rRNA gene sequencing: a systematic review and meta-analysis.

PURPOSE: Breast cancer (BC) is a devastating disease for women. Microbial influences may be involved in the development and progression of breast cancer. This study aimed to investigate the difference in intestinal flora abundance between breast cancer patients and healthy controls (HC) based on previous 16S ribosomal RNA (rRNA) gene sequencing results, which have been scattered and inconsistent in previous studies. MATERIALS AND METHODS: In agreement with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), we searched for pertinent literature in Pubmed, Embase, Cochrane Library, and Web of Science databases from build until February 1, 2023. Relative abundance, diversity of intestinal microflora by level, microbial composition, community structure, diversity index, and other related data were extracted. We used a fixed or random effects model for data analysis. We also conducted funnel plot analysis, sensitivity analysis, Egger's, and Begg's tests to assess the bias risk. RESULTS: A total of ten studies involving 734 BC patients were enrolled. It was pointed out that there were significant differences in the Chao index between BC and HC in these studies [SMD = - 175.44 (95% CI - 246.50 to - 104.39)]. The relative abundance of Prevotellaceae [SMD = - 0.27 (95% CI - 0.39 to - 0.15)] and Bacteroides [SMD = 0.36 (95% CI 0.23-0.49)] was significantly different. In the included articles, the relative abundance of Prevotellaceae, Ruminococcus, Roseburia inulinivorans, and Faecalibacterium prausnitzii decreased in BC. Accordingly, the relative richness of Erysipelotrichaceae was high in BC. CONCLUSIONS: This observational meta-analysis revealed that the changes in gut microbiota were correlated with BC, and the changes in some primary fecal microbiota might affect the beginning of breast cancer.

Dynamic modelling and inverse compensation for coupled hysteresis in pneumatic artificial muscle-actuated soft manipulator with variable stiffness.

The soft manipulator actuated parallel with contractile and extensor pneumatic artificial muscles (PAMs) can perform continuous operations and vary stiffness. Due to the hysteresis nonlinearity of PAMs and parallel driving, the manipulator shows coupled hysteresis with stiffness-dependent and rate-dependent characteristics, causing inaccurate positioning performance. This paper firstly proposes a comprehensive dynamic model consisting of two parts in series to predict the manipulator dynamical behaviors with coupled hysteresis. Furthermore, a decoupled inverse compensation and decoupling control on the basis of the proposed model is conducted on the soft manipulator. Experimental results and comparisons illustrate the high precision and strong generalization ability of the proposed model and the validity of the compensator in mitigating the coupled dynamic hysteresis of the system.

THEM6 is a prognostic biomarker for breast cancer and is associated with immune infiltration.

To characterize the implications of lipid metabolism-related gene thioesterase superfamily member 6 (THEM6) in breast cancer. Several databases including The Cancer Genome Atlas (TCGA) were utilized for our meticulous bioinformatics analysis. We further performed qRT-PCR, immunoblotting and IHC assays to validate the expression of THEM6 in various breast cancer cells and tissues. In addition, we have carried out relevant functional experiments to explore the regulatory role of THEM6 in vitro. Lipid metabolism-related genes are independent factors for overall survival. According to several databases, THEM6 was significantly more expressed in cancerous tissues of breast invasive carcinoma (BRCA) compared to its paracancerous tissues. Furthermore, THEM6 overexpression was correlated with poorer overall survival of BRCA patients, serving as a separate prognostic factor for BRCA. Biological functional analyses revealed that THEM6 was associated with tumor progression and pathogenesis. Finally, we discovered that in BRCA, THEM6 expression was linked to multiple immune cell types. qRT-PCR and Western blotting experiments demonstrated a general upregulation of THEM6 expression in breast carcinoma cells. IHC showed that THEM6 was expressed in both breast cancer tissues and para-cancer tissues, but its expression level was significantly higher in carcinoma tissues. In vitro studies indicated that THEM6 increased proliferation, invasion, and inhibited apoptosis of breast carcinoma cells, while also affecting the cell cycle and promoting cancer progression. Furthermore, THEM6 may influence macrophage recruitment and polarization in the tumor microenvironment by regulating CCL2 secretion, which in turn affects macrophage recruitment in the tumor microenvironment. Our findings indicate that the overexpression of THEM6, which is linked to the development of breast cancer, is a predictor of a poor prognosis and has an impact on the degree of immune cell infiltration. Therefore, THEM6 has the potential to be a valuable target for BRCA.

Low-level mosaic trisomy 21 at amniocentesis in a pregnancy associated with cytogenetic discrepancy in various tissues, perinatal progressive decrease of the trisomy 21 cell line and a favorable fetal outcome.

OBJECTIVE: We present low-level mosaic trisomy 21 at amniocentesis in a pregnancy associated with cytogenetic discrepancy in various tissues, perinatal progressive decrease of the trisomy 21 cell line and a favorable fetal outcome. CASE REPORT: A 36-year-old, gravida 2, para 1, woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age, and the result was 47,XY,+21 [8]/46,XY [26]. Prenatal ultrasound findings were unremarkable. She was referred for genetic counseling, and repeat amniocentesis performed at 23 weeks of gestation revealed the result of 47,XY,+21 [3]/46,XY [21]. The parental karyotypes were normal. At repeat amniocentesis, quantitative fluorescent polymerase chain reaction (QF-PCR) analysis using the DNA extracted from uncultured amniocytes and parental bloods excluded uniparental disomy (UPD) 21, array comparative genomic hybridization (aCGH) analysis on uncultured amniocytes revealed the result of arr 21q11.2q22.3 × 2.4, consistent with 40% mosaicism for trisomy 21, and fluorescence in situ hybridization (FISH) analysis on uncultured amniocytes revealed 67% (67/100 cells) mosaicism for trisomy 21. The woman was advised to continue the pregnancy, and a 1370-g male baby was delivered prematurely at 29 weeks of gestation without phenotypic abnormalities. The karyotypes of umbilical cord and placenta were 47,XY,+21 [13]/46,XY [27] and 47,XY,+21 [40], respectively. QF-PCR determined maternal origin of the extra chromosome 21 of trisomy 21 in the placenta. When follow-up at age 8½ months, the neonate was normal in appearance and development. The peripheral blood had a karyotype of 47,XY,+21 [1]/46,XY [39], and FISH analysis on buccal mucosal cells showed 9.7% (11/113 cells) mosaicism for trisomy 21, compared with 2% (2/100 cells) in the normal control. CONCLUSION: Low-level mosaic trisomy 21 at amniocentesis can be associated with cytogenetic discrepancy in various tissues, perinatal progressive decrease of the trisomy 21 cell line and a favorable fetal outcome.

High-level mosaic trisomy 21 at amniocentesis in a pregnancy associated with positive NIPT for trisomy 21, prenatal progressive decrease of the trisomy 21 cell line, acute fatty liver of pregnancy and intrauterine fetal death in late gestation.

OBJECTIVE: We present high-level mosaic trisomy 21 at amniocentesis in a pregnancy associated with positive non-invasive prenatal testing (NIPT) for trisomy 21, prenatal progressive decrease of the trisomy 21 cell line, acute fatty liver of pregnancy and intrauterine fetal death (IUFD) in late gestation. CASE REPORT: A 32-year-old, primigravid woman underwent amniocentesis at 17 weeks of gestation because of positive NIPT for trisomy 21 at 12 weeks of gestation. This pregnancy was conceived by in vitro fertilization. She did not have obesity, diabetes mellitus, hepatic biliary disorders and preeclampsia. Amniocentesis revealed a karyotype of 47,XY,+21[10]/46,XY[11], and array comparative genomic hybridization (aCGH) analysis on uncultured amniocytes revealed the result of arr (21) × 2-3. She was referred for genetic counseling, and repeat amniocentesis performed at 21 weeks of gestation revealed the karyotype of 47,XY,+21[10]/46,XY[28]. The parental karyotypes and fetal ultrasound findings were normal. Simultaneous molecular analysis on uncultured amniocytes showed no uniparental disomy 21, but a maternal origin of trisomy 21 by quantitative fluorescent polymerase chain reaction (QF-PCR) and the result of arr 21q11.2q22.3 × 2.5 by aCGH analysis. At 27 weeks of gestation, she underwent a third amniocentesis, of which conventional cytogenetic analysis revealed the result of 47,XY,+21[5]/46,XY[17] in cultured amniocytes, and aCGH analysis revealed arr 21q11.2q22.3 × 2.48, and interphase fluorescence in situ hybridization (FISH) analysis revealed 39% (39/100 cells) mosaicism fro trisomy 21 in uncultured amniocytes. At 36 weeks of gestation, the woman suffered from a sudden onset of acute fatty liver and IUFD. A 3522-g male baby was delivered without Down syndrome phenotype. The umbilical cord had a karyotype of 47,XY,+21[10]/46,XY[30]. aCGH analysis on the skin and placenta showed arr 21q11.2q22.3 × 2.73 and arr 21q11.2q22.3 × 2.75, respectively. QF-PCR analysis of umbilical cord, placenta and skin showed a maternal origin of trisomy 21. CONCLUSION: High-level mosaic trisomy 21 at amniocentesis can be associated with prenatal progressive decrease of the trisomy 21 cell line in cultured amniocytes and perinatal fetal mortality and maternal morbidity.

45,X/46,XX at the first amniocentesis, and 45,X/47,XXX/46,XX at the repeat amniocentesis and at birth in a pregnancy associated with a favorable fetal outcome, perinatal progressive decrease of the 45,X cell line and cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes.

OBJECTIVE: We present 45,X/46,XX at the first amniocentesis, and 45,X/47,XXX/46,XX at the repeat amniocentesis and at birth in a pregnancy associated with a favorable fetal outcome, perinatal progressive decrease of the 45,X cell line and cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes. CASE REPORT: A 43-year-old, gravida 3, para 1, woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 45,X[4]/46,XX[20]. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed arr (X) × 3 [0.24], consistent with 24% mosaicism for triple X. Repeat amniocentesis at 20 weeks of gestation revealed the result of 45,X[17]/47,XXX[8]/46,XX[121]. She was referred for genetic counseling, and the third amniocentesis performed at 30 weeks of gestation revealed the result of 45,X[3]/47,XXX[2]/46,XX[16]. The mother had a karyotype of 46,XX. aCGH analysis on the DNA extracted from uncultured amniocytes showed arr Xp22.33q28 × 2.2 (log2 ratio = 0.15), consistent with 20% mosaicism for triple X. Interphase fluorescence in situ hybridization (FISH) analysis on 100 uncultured amniocytes showed that 11 cells (11%) were monosomy X, seven cells (7%) were triple X, and the others were disomy X. At 39 weeks of gestation, a 3,620-g phenotypically normal female baby was delivered without any phenotypic abnormality. The karyotypes of cord blood, umbilical cord and placenta were 47,XXX[7]/45,X[1]/46,XX[32], 47,XXX[13]/46,XX[27] and 47,XXX[2]/46,XX[38], respectively. When follow-up at age one month, the neonate was phenotypically normal, and FISH analysis on 106 buccal mucosal cells showed that eight cells (7.5%) were monosomy X, seven cells (6.6%) were triple X, and the others were disomy X. CONCLUSION: Mosaic 45,X/46,XX at amniocentesis may be in fact mosaic 45,X/47,XXX/46,XX and can be associated with a favorable fetal outcome and perinatal progressive decrease of the 45,X cell line.

Perinatal detection of disomy X cell line by fluorescence in situ hybridization in a pregnancy with 45,X/47,XXX at amniocentesis, cytogenetic discrepancy in various tissues and a favorable outcome.

OBJECTIVE: We present perinatal detection of disomy X cell line by fluorescence in situ hybridization (FISH) in a pregnancy with 45,X/47,XXX at amniocentesis, cytogenetic discrepancy in various tissues and a favorable outcome. CASE REPORT: A 34-year-old, gravida 3, para 1, woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 45,X[22]/47,XXX[10]. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed the result of arr (X) × 1-2, (1-22) × 2, consistent with 32% mosaicism for monosomy X. She was referred for genetic counseling at 19 weeks of gestation. Prenatal ultrasound findings and parental karyotypes were normal. Repeat amniocentesis at 29 weeks of gestation revealed a karyotype of 45,X[36]/47,XXX[4] (Fig. 1) in cultured amniocytes. Simultaneous molecular analysis on uncultured amniocytes revealed the result of arr (1-22) × 2, Y × 0 by aCGH with no genomic imbalance, and 15% (15/100 cells) mosaicism for disomy X, 61% (61/100 cells) mosaicism for monosomy X and 24% (24/100 cells) mosaicism for triple X by interphase fluorescence in situ hybridization (FISH) analysis. The pregnancy was encouraged to continue and at 37 weeks of gestation, a 2834-g phenotypically normal female baby was delivered. The karyotypes of cord blood, umbilical cord and placenta were 45,X[33]/47,XXX[7], 45,X[30]/47,XXX[10] and 47,XXX[38]/45,X[2], respectively. When follow-up at age three months, the neonate was normal in development. FISH analysis on 99 buccal mucosal cells showed 49% (48/99 cells) mosaicism for monosomy X, 8% (8/99 cells) mosaicism for triple X and 43% (42/99 cells) mosaicism for disomy X (Fig. 2). Peripheral blood had a karyotype of 45,X[38]/47,XXX[2]. When follow-up at age nine months, the neonate was normal in development. FISH analysis on 102 buccal mucosal cells showed 11% (11/102 cells) mosaicism for monosomy X, 12% (12/102 cells) mosaicism for triple X and 77% (79/102 cells) mosaicism for disomy X. Peripheral blood had a karyotype of 45,X[30]/47,XXX[10]. CONCLUSION: 45,X/47,XXX at amniocentesis may detect disomy X cell line by FISH analysis and can be associated with postnatal progressive decrease of the aneuploid cell lines, increase of the disomy X cell line and a favorable outcome.