Progress and recognition of idiopathic intracranial hypertension: A narrative review.

BACKGROUND: Idiopathic intracranial hypertension (IIH) mainly affects obese young women, causing elevated intracranial pressure, headaches, and papilledema, risking vision loss and severe headaches. Despite weight loss as the primary treatment, the underlying mechanisms remain unclear. Recent research explores novel therapeutic targets. AIMS: This review aimed to provide a comprehensive understanding of IIH's pathophysiology and clinical features to inform pathogenesis and improve treatment strategies. METHODS: Recent publications on IIH were searched and summarized using PubMed, Web of Science, and MEDLINE. RESULTS: The review highlights potential pathomechanisms and therapeutic advances in IIH. CONCLUSION: IIH incidence is rising, with growing evidence linking it to metabolic and hormonal disturbances. Early diagnosis and treatment remain challenging.

Lnc NBAT1 Inhibits the Proliferation and Migration of Liver Cancer Cells Through the miR-21/PDCD4/AP-1 Signaling Axis.

Long non-coding RNAs (Lnc RNAs) are proven to participate in liver cancer (LC) regulation. The regulation of miR-21 by lnc NBAT1 has been studied in other cancers. However, the effect of this regulation on LC and its specific mechanism remains unclear. Lnc NBAT1 and miR-21 expressions in clinical tissues were measured by RT-qPCR. PDCD4, AP-1, p-c-Fos, p-c-Jun, and cyclin D1 expressions were analyzed by Western blot. Overexpression of lnc NBAT1 was studied to explore its influence on malignant behaviors of Bel7402 cells and the development of LC in the xenograft mouse model (XMM). The regulation mechanism of lnc NBAT1 in LC was explored by lnc NBAT1 overexpression, miR-21 mimic treatment, or PDCD4 silencing in Bel7402 cells. Lnc NBAT1 expression was downregulated while miR-21 expression was upregulated in LC tissues and cell lines. In comparison with LX-2 cells, the expressions of PDCD4 and AP-1 were downregulated in Bel7402 cells, while those of p-c-Fos, p-c-Jun, and cyclin D1 were upregulated. Further, lnc NBAT1 was found to localize primarily in the cytoplasm of Bel7402 cells. Overexpression of lnc NBAT1 enhanced cell apoptosis, blocked the cell cycle, suppressed malignant behaviors of Bel7402 cells, and inhibited tumor progression in the XMM. Mechanistically, lnc NBAT1 functioned as a competing endogenous RNA (ceRNA) by binding to the downstream target miR-21 to stabilize the expressions of PDCD4 and AP-1, thereby inhibiting malignant behaviors of Bel7402 cells. Lnc NBAT1 suppressed malignant behaviors of LC cells through the miR-21/PDCD4/AP-1 axis. Lnc NBAT1 might be a promising biomarker for LC treatment.

Is fluorometric sentinel lymph node biopsy in endometrial cancer necessary?

Objective: In this study, we collected perioperative and postoperative follow-up data from patients with endometrial cancer (EC) at different stages to evaluate the role of sentinel lymph node biopsy (SLNB) in endometrial cancer surgery. Methods: A total of 186 endometrial cancer patients undergoing radical hysterectomy from January 2018 to April 2022 were retrospectively analyzed. Patients were classified into four groups. Group A comprised patients diagnosed with stage IA grade 1 and 2 endometrioid EC who underwent SLNB. Group B comprised patients with stage IA grade 1 and 2 endometrioid EC who did not undergo SLNB. Group C comprised patients with higher-grade endometrioid EC, wherein systematic lymph node dissection was performed based on SLNB results. Group D comprised patients with higher-grade endometrioid EC who did not undergo SLNB and instead underwent direct systematic lymph node dissection. Clinical, pathological data, and follow-up information for all patients were collected. Results: In Group A and B, SLNB was performed on 36 out of 67 patients with IA stage 1 and 2 endometrial cancer, yielding a SLN positivity rate of 5.6%. There were no significant differences observed between the two groups regarding perioperative outcomes and postoperative follow-up. Conversely, among 119 patients with higher-grade endometrial cancer, 52 underwent SLNB, with 20 patients exhibiting SLN positivity, resulting in a SLN positivity rate of 38.4%. However, the decision to undergo SLNB did not yield significant differences in perioperative outcomes and postoperative follow-up among these patients. Conclusion: For stage IA grade 1 and 2 endometrioid EC, the incidence of lymph node positivity is low, omitting SLNB in this subpopulation is a feasible option. In other stages of endometrioid EC, there is no significant difference in perioperative and postoperative follow-up data between patients undergoing routine systematic lymphadenectomy and those undergoing systematic lymphadenectomy based on SLNB results. Therefore, if SLNB is not available, the standard procedure of PLND remains an option to obtain information about lymph node status, despite the surgical complications associated with this procedure.

Clinical Characteristic and Tear Film Biomarkers After Myopic FS-LASIK: 1-Year Prospective Follow-up.

PURPOSE: To assess the long-term (1-year) effect of myopic femtosecond laser-assisted in situ keratomileusis (FSLASIK) on clinical characteristics and tear film biomarkers. METHODS: Eighty eyes from 80 patients who underwent FSLASIK were evaluated. Ocular surface symptoms and signs were evaluated using specific questionnaires and tests. The corneal nerves and dendritic cells were examined using in vivo confocal microscopy. Corneal sensitivity was evaluated using a Cochet-Bonnet esthesiometer. Tear inflammatory cytokines and neuropeptides were evaluated using Luminex immunoassay. These examinations were performed preoperatively and at 1, 3, 6, and 12 months postoperatively. RESULTS: Seventy-three participants completed all follow-up visits. Following FS-LASIK, ocular symptoms and signs (except Schirmer I test) worsened at 1 month but corneal and conjunctival stainings improved by 3 months. The numbers of dendritic cells and activated dendritic cells increased at the 3-month postoperative visit and recovered to preoperative levels by the 6-month visit. Ocular symptoms and corneal sensitivity recovered to preoperative levels at the 12-month visit. Tear break-up time and corneal nerve morphology were not recovered to preoperative status at the 12-month visit. Interleukin (IL)-1ß, IL-17A, tumor necrosis factor-α, and substance P tear levels significantly increased at all postoperative visits compared to preoperative levels. Corneal staining scores positively correlated with tear IL-1ß and IL-17A levels, whereas corneal nerve morphology positively correlated with corneal sensitivity and negatively correlated with substance P levels. CONCLUSIONS: Although most clinical variables improved at 12 months postoperatively, some tear inflammatory cytokines and substance P remain altered beyond 12 months, indicating that ocular homeostasis is not completely recovered. [J Refract Surg. 2024;40(8):e508-e519.].

KHSRP Stabilizes m6A-Modified Transcripts to Activate FAK Signaling and Promote Pancreatic Ductal Adenocarcinoma Progression.

N6-methyladenosine (m6A) is the most prevalent RNA modification and is associated with various biological processes. Proteins that function as readers and writers of m6A modifications have been shown to play critical roles in human malignancies. Here, we identified KH-type splicing regulatory protein (KHSRP) as an m6A binding protein that contributes to the progression of pancreatic ductal adenocarcinoma (PDAC). High KHSRP levels were detected in PDAC and predicted poor patient survival. KHSRP deficiency suppressed PDAC growth and metastasis in vivo. Mechanistically, KHSRP recognized and stabilized FAK pathway mRNAs, including MET, ITGAV and ITGB1, in an m6A-dependent manner, which led to activation of downstream FAK signaling that promoted PDAC progression. Targeting KHSRP with a PROTAC showed promising tumor suppressive effects in mouse models, leading to prolonged survival. Together, these findings indicate that KHSRP mediates FAK pathway activation in an m6A-dependent manner to support PDAC growth and metastasis, highlighting the potential of KHSRP as a therapeutic target in pancreatic cancer.

Dry eye disease adverse reaction of pharmacological treatment for early-stage breast cancer.

Breast cancer is the most prevalent cancer worldwide. With advancements in breast cancer diagnosis and treatment, the prognosis of patients with early-stage cancer has significantly improved. Enhancing the long-term quality of life of patients after antineoplastic therapy, including visual quality, has become a crucial research focus. This review aims to comprehensively summarize dry eye disease adverse reaction resulting from pharmacotherapy for early-stage breast cancer. Through a review of the relevant literature, this study explored the etiology, clinical features, and potential therapeutic strategies for drug-induced dry eye disease in breast cancer treatment. A thorough understanding of the medication-induced dry eye disease adverse reaction aid clinicians in monitoring and managing patients' ocular health more effectively, facilitating early diagnosis and intervention, preventing complications, and ensuring optimal visual protection for patients undergoing breast cancer treatment.

Clinical Features and Histopathological Analysis of Oral Lichen Planus: An Analysis of 105 Chinese Patients.

PURPOSE: To study the clinical and pathological characteristics of oral lichen planus (OLP) in a large sample. MATERIALS AND METHODS: A comprehensive analysis was conducted on 105 patients with oral lichen planus (OLP), considering various factors including sex, age, disease site, lesion type, lesion area, morphological characteristics, self-reported symptoms, and history of systemic diseases. Histopathological examination was performed for each patient, and the pathology results were analysed according to sex and age group. RESULTS: 70.5% of the OLP patients were female, and OLP was most likely to occur in the cheek, followed by the tongue, lips, gums and palate. The patients with moderate pain according to the VAS score accounted for 60%. Thirty-nine percent of the OLP patients had a systemic disease, and the most common clinical type of OLP was nonerosive. Most of the pathological results showed liquefaction degeneration of basal cells and infiltration of lamina propria lymphocytes. There was no statistically significant difference in pathological manifestations between male and female patients, and there were statistically significant differences in pathological manifestations among different ages patients. CONCLUSION: This study analysed the sociodemographic data and clinical manifestations of 105 OLP patients to guide follow-up treatment planning and disease monitoring. Moreover, pathological manifestations should be analysed to avoid delayed treatment and to monitor for carcinogenesis. Furthermore, the correlation of pathological manifestations among OLP patients with different sexes and ages is conducive to further research on the specific differential manifestations and possible underlying mechanisms involved.

Destructive Cryptococcal Osteomyelitis Mimicking Tuberculous Spondylitis.

BACKGROUND Cryptococcosis is an opportunistic fungal infection that typically occurs in patients with compromised immune systems, primarily affecting the respiratory and central nervous systems. However, cryptococcal osteomyelitis is a rare manifestation of cryptococcal infection, characterized by nonspecific clinical features. Here, we present a case of vertebral cryptococcal osteomyelitis in a middle-aged woman and discuss diagnostic approaches. CASE REPORT A 56-year-old woman presented with lower back pain and limited mobility, without fever, and with a history of pulmonary tuberculosis. Physical examination revealed enlarged lymph nodes and tenderness in the thoracic vertebrae. A computed tomography-guided biopsy confirmed granulomatous inflammation caused by Cryptococcus, with abundant 10 µm spherical microbial spores. After 4 weeks of treatment with amphotericin B and fluconazole, symptoms and lesions improved. Upon discharge, the patient was prescribed oral fluconazole. Follow-up examinations showed a stable condition and a negative serum cryptococcal capsular polysaccharide antigen test. CONCLUSIONS Given the rarity and lack of specificity of clinical features of cryptococcal spondylitis, clinicians encountering similar presentations should consider tuberculous spondylitis and spinal tumors as differential diagnoses. Additionally, tissue biopsy of the affected vertebral bodies should be performed early to establish the type of vertebral infection, aiding in diagnosis, treatment, and prognosis.

ZBTB20 suppresses tumor growth in glioblastoma through activating the TET1/FAS/caspase­3 pathway.

Zinc finger and BTB domain containing 20 (ZBTB20) is a key transcription repressor that regulates multiple physiological and pathophysiological processes. Thus far, the role of ZBTB20 in glioblastoma (GBM), a World Health Organization grade IV glioma, remains unclear. In the present study, the expression profile data of ZBTB20 in GBM tissues from public databases was analyzed. It was found that ZBTB20 expression in GBM tissues was significantly lower than that measured in lower grade glioma tissues. Furthermore, patients with GBM with lower ZBTB20 expression were associated with a shorter overall survival time. Gain- and loss-of-function experiments in GBM cells were also performed. The results demonstrated that ZBTB20 overexpression decreased GBM cell proliferation, while ZBTB20 knockdown significantly enhanced it. Cell cycle analysis showed the ZBTB20 overexpression may have inhibited proliferation through cell cycle arrest at the G2/M phase, while ZBTB20 knockdown increased the percentages of cells in both the S phase and G2/M phase. Ten-eleven translocation 1 (TET1) is an important tumor suppressor involved in the formation of various types of tumor, and it was upregulated in ZBTB20-overexpressing GBM cells. It was further demonstrated that ZBTB20 activated the TET1/FAS/caspase-3 pathway. The results of the present study therefore indicated the potential role of ZBTB20 as a tumor suppressor and therapeutic target for GBM.

Impact of Topical 0.05% Cyclosporine A Eye Drops on Post-Femtosecond-Assisted Laser In Situ Keratomileusis Ocular Surface Recovery: A Randomized Clinical Trial.

OBJECTIVES: To investigate the effect of topical 0.05% cyclosporine A (CsA) eye drops as an adjunct to conventional therapy in maintaining post-femtosecond-assisted laser in situ keratomileusis (FS-LASIK) ocular surface stability. METHODS: Sixty-six patients (eyes) undergoing FS-LASIK were randomized into 2 groups: 33 patients (eyes) in group I (conventional treatment group) and 33 patients (eyes) in group II (CsA group). Conventional treatments include topical levofloxacin, fluorometholone, and artificial tears. Group II received topical 0.05% CsA eye drops twice daily for three months in addition to conventional treatment. Ocular Surface Disease Index (OSDI), numerical rating scale (NRS), tear break-up time (TBUT), Schirmer I test (SIt), corneal fluorescein staining (CFS), conjunctival lissamine green (LG) staining, corneal sensitivity, and corneal nerve morphology were measured. In addition, tear inflammatory cytokine levels were measured using the Luminex assay. Follow-up was performed preoperatively and 1 and 3 months postoperatively. RESULTS: In the CsA group, OSDI, TBUT, LG, corneal sensitivity, and corneal nerve fiber total branch density recovered better than in the conventional treatment group. As for tear inflammatory cytokines, interferon (INF) -γ, interleukin (IL)-10, and IL-6 levels were significantly higher in the conventional treatment group as compared with the CsA group. In addition, no significant differences in NRS, SIt, and CFS scores were observed between the two groups. CONCLUSION: In conclusion, 0.05% CsA eye drops is a useful adjunct to conventional treatment for restoring the ocular surface stability after corneal refractive surgery and is more potent in sustaining anti-inflammatory effects.

A Study on the Growth and Physiological Toxicity Effects of the Combined Exposure of Microplastics and Cadmium on the Vicia faba L. Seedlings.

To investigate the toxicological effects of polystyrene microplastics (PS-MPs), cadmium (Cd), and their combined contamination on the growth and physiological responses of V. faba seedlings, this experiment employed a hydroponic method. The Hoagland nutrient solution served as the control, changes in root growth, physiological and biochemical indicators of V. faba seedlings under different concentrations of PS-MPs (10, 100 mg/L) alone and combined with 0.5 mg/L Cd. The results demonstrated that the root biomass, root vitality, generation rate of superoxide radicals (O2·-), malondialdehyde (MDA) content, and superoxide dismutase (SOD) activity increased with increasing concentration under the influence of PS-MPs alone, while the soluble sugar content and peroxidase (POD) activity decreased. In the combined treatment with Cd, the trends of these indicators are generally similar to the PS-MPs alone treatment group. However, root vitality and SOD activity showed an inverse relationship with the concentration of PS-MPs. Furthermore, laser confocal and electron microscopy scanning revealed that the green fluorescent polystyrene microspheres entered the root tips of the V. faba and underwent agglomeration in the treatment group with a low concentration of PS-MPs alone and a high concentration of composite PS-MPs with Cd.

Prevotella intermedia boosts OSCC progression through ISG15 upregulation: a new target for intervention.

PURPOSE: Periodontitis-associated bacteria, such as Porphyromonas gingivalis and Fusobacterium nucleatum, are closely linked to the risk of oral squamous cell carcinoma (OSCC). Emerging studies have indicated that another common periodontal pathogen, Prevotella intermedia (P. intermedia), is enriched in OSCC and could affect the occurrence and progression of OSCC. Our aim is to determine the effects of P. intermedia on the progression of OSCC and the role of antibiotics in reversing these effects. METHODS: In this study, a murine xenograft model of OSCC was established, and the mice were injected intratumorally with PBS (control group), P. intermedia (P.i group), or P. intermedia combined with an antibiotic cocktail administration (P.i + ABX group), respectively. The effects of P. intermedia and ABX administration on xenograft tumor growth, invasion, angiogenesis, and metastasis were investigated by tumor volume measurement and histopathological examination. Enzyme-linked immunosorbent assay (ELISA) was used to investigate the changes in serum cytokine levels. Immunohistochemistry (IHC) was adopted to analyze the alterations in the levels of inflammatory cytokines and infiltrated immune cells in OSCC tissues of xenograft tumors. Transcriptome sequencing and analysis were conducted to determine differential expression genes among various groups. RESULTS: Compared with the control treatment, P. intermedia treatment significantly promoted tumor growth, invasion, angiogenesis, and metastasis, markedly affected the levels of inflammatory cytokines, and markedly altered M2 macrophages and regulatory T cells (Tregs) infiltration in the tumor microenvironment. However, ABX administration clearly abolished these effects of P. intermedia. Transcriptome and immunohistochemical analyses revealed that P. intermedia infection increased the expression of interferon-stimulated gene 15 (ISG15). Correlation analysis indicated that the expression level of ISG15 was positively correlated with the Ki67 expression level, microvessel density, serum concentrations and tissue expression levels of inflammatory cytokines, and quantities of infiltrated M2 macrophages and Tregs. However, it is negatively correlated with the quantities of infiltrated CD4+ and CD8+ T cells. CONCLUSION: In conclusion, intratumoral P. intermedia infection aggravated OSCC progression, which may be achieved through upregulation of ISG15. This study sheds new light on the possible pathogenic mechanism of intratumoral P. intermedia in OSCC progression, which could be a prospective target for OSCC prevention and treatment.

QDPR deficiency drives immune suppression in pancreatic cancer.

The relevance of biopterin metabolism in resistance to immune checkpoint blockade (ICB) therapy remains unknown. We demonstrate that the deficiency of quinoid dihydropteridine reductase (QDPR), a critical enzyme regulating biopterin metabolism, causes metabolite dihydrobiopterin (BH2) accumulation and decreases the ratio of tetrahydrobiopterin (BH4) to BH2 in pancreatic ductal adenocarcinomas (PDACs). The reduced BH4/BH2 ratio leads to an increase in reactive oxygen species (ROS) generation and a decrease in the distribution of H3K27me3 at CXCL1 promoter. Consequently, myeloid-derived suppressor cells are recruited to tumor microenvironment via CXCR2 causing resistance to ICB therapy. We discovered that BH4 supplementation is capable to restore the BH4/BH2 ratio, enhance anti-tumor immunity, and overcome ICB resistance in QDPR-deficient PDACs. Tumors with lower QDPR expression show decreased responsiveness to ICB therapy. These findings offer a novel strategy for selecting patient and combining therapies to improve the effectiveness of ICB therapy in PDAC.

Role of microvascular invasion in early recurrence of hepatocellular carcinoma after liver resection: A literature review.

Hepatectomy is widely considered a potential treatment for hepatocellular carcinoma (HCC). Unfortunately, one-third of HCC patients have tumor recurrence within 2 years after surgery (early recurrence), accounting for more than 60% of all recurrence patients. Early recurrence is associated with a worse prognosis. Previous studies have shown that microvascular invasion (MVI) is one of the key factors for early recurrence and poor prognosis in patients with HCC after surgery. This paper reviews the latest literature and summarizes the predictors of MVI, the correlation between MVI and early recurrence, the identification of suspicious nodules or subclinical lesions, and the treatment strategies for MVI-positive HCC. The aim is to explore the management of patients with MVI-positive HCC.

STAT3 protects hematopoietic stem cells by preventing activation of a deleterious autocrine type-I interferon response.

Hematopoietic stem and progenitor cells (HSPCs) maintain blood-forming and immune activity, yet intrinsic regulators of HSPCs remain elusive. STAT3 function in HSPCs has been difficult to dissect as Stat3-deficiency in the hematopoietic compartment induces systemic inflammation, which can impact HSPC activity. Here, we developed mixed bone marrow (BM) chimeric mice with inducible Stat3 deletion in 20% of the hematopoietic compartment to avoid systemic inflammation. Stat3-deficient HSPCs were significantly impaired in reconstitution ability following primary or secondary bone marrow transplantation, indicating hematopoietic stem cell (HSC) defects. Single-cell RNA sequencing of Lin-ckit+Sca1+ BM cells (LSKs) revealed aberrant activation of cell cycle, p53, and interferon (IFN) pathways in Stat3-deficient HSPCs. Stat3-deficient LSKs accumulated γH2AX and showed increased expression of DNA sensors and type-I IFN (IFN-I), while treatment with A151-ODN inhibited expression of IFN-I and IFN-responsive genes. Further, the blockade of IFN-I receptor signaling suppressed aberrant cell cycling, STAT1 activation, and nuclear p53 accumulation. Collectively, our results show that STAT3 inhibits a deleterious autocrine IFN response in HSCs to maintain long-term HSC function. These data signify the importance of ensuring therapeutic STAT3 inhibitors are targeted specifically to diseased cells to avoid off-target loss of healthy HSPCs.

Heat-killed Prevotella intermedia promotes the progression of oral squamous cell carcinoma by inhibiting the expression of tumor suppressors and affecting the tumor microenvironment.

BACKGROUND: Oral microbial dysbiosis contributes to the development of oral squamous cell carcinoma (OSCC). Our previous study showed that Prevotella intermedia (P. intermedia) were enriched in the oral mucosal surface, plaque, and saliva of patients with OSCC. Intratumoral microbiome could reshape the immune system and influence the development of various tumors. However, the invasion status of human OSCC tissues by P. intermedia and the pathway through which intratumoral P. intermedia potentiates tumor progression remain unexplored. METHODS: P. intermedia in human OSCC or normal tissues was detected by FISH. A mouse OSCC cell line SCC7 was adopted to investigate the effects of heat-killed P. intermedia treatment on cell proliferation, invasion, and cytokine release by using CCK-8 assay, transwell invasion assay and ELISA. Moreover, we established a mouse transplanted tumor model by using SCC7 cells, injected heat-killed P. intermedia into tumor tissues, and investigated the effects of heat-killed P. intermedia on tumor growth, invasion, cytokine levels, immune cell infiltrations, and expression levels by using gross observation, H&E staining, ELISA, immunohistochemistry, mRNA sequencing, and transcriptomic analysis. RESULTS: Our results indicated that P. intermedia were abundant in OSCC and surrounding muscle tissues. Heat-killed P. intermedia promoted SCC7 cell proliferation, invasion and proinflammatory cytokine secretions, accelerated transplanted tumor growth in mice, exacerbate muscle and perineural invasion of OSCC, elevated the serum levels of IL-17A, IL-6, TNF-α, IFN-γ, and PD-L1, induced Treg cells M2 type macrophages in mouse transplanted tumors. The data of transcriptomic analysis revealed that heat-killed P. intermedia increased the expression levels of inflammatory cytokines and chemokines while reduced the expression levels of some tumor suppressor genes in mouse transplanted tumors. Additionally, IL-17 signaling pathway was upregulated whereas GABAergic system was downregulated by heat-killed P. intermedia treatment. CONCLUSIONS: Taken together, our results suggest that P. intermedia could inhibit the expression of tumor suppressors, alter the tumor microenvironment, and promote the progression of OSCC.

Impact of CRISPR/HDR editing versus lentiviral transduction on long-term engraftment and clonal dynamics of HSPCs in rhesus macaques.

For precise genome editing via CRISPR/homology-directed repair (HDR), effective and safe editing of long-term engrafting hematopoietic stem cells (LT-HSCs) is required. The impact of HDR on true LT-HSC clonal dynamics in a relevant large animal model has not been studied. To track the output and clonality of HDR-edited cells and to provide a comparison to lentivirally transduced HSCs in vivo, we developed a competitive rhesus macaque (RM) autologous transplantation model, co-infusing HSCs transduced with a barcoded GFP-expressing lentiviral vector (LV) and HDR edited at the CD33 locus. CRISPR/HDR-edited cells showed a two-log decrease by 2 months following transplantation, with little improvement via p53 inhibition, in comparison to minimal loss of LV-transduced cells long term. HDR long-term clonality was oligoclonal in contrast to highly polyclonal LV-transduced HSCs. These results suggest marked clinically relevant differences in the impact of current genetic modification approaches on HSCs.

Integrated multiomic profiling of breast cancer in the Chinese population reveals patient stratification and therapeutic vulnerabilities.

Molecular profiling guides precision treatment of breast cancer; however, Asian patients are underrepresented in publicly available large-scale studies. We established a comprehensive multiomics cohort of 773 Chinese patients with breast cancer and systematically analyzed their genomic, transcriptomic, proteomic, metabolomic, radiomic and digital pathology characteristics. Here we show that compared to breast cancers in white individuals, Asian individuals had more targetable AKT1 mutations. Integrated analysis revealed a higher proportion of HER2-enriched subtype and correspondingly more frequent ERBB2 amplification and higher HER2 protein abundance in the Chinese HR+HER2+ cohort, stressing anti-HER2 therapy for these individuals. Furthermore, comprehensive metabolomic and proteomic analyses revealed ferroptosis as a potential therapeutic target for basal-like tumors. The integration of clinical, transcriptomic, metabolomic, radiomic and pathological features allowed for efficient stratification of patients into groups with varying recurrence risks. Our study provides a public resource and new insights into the biology and ancestry specificity of breast cancer in the Asian population, offering potential for further precision treatment approaches.