The ZMYND8-regulated mevalonate pathway endows YAP-high intestinal cancer with metabolic vulnerability.

Cholesterol metabolism is tightly associated with colorectal cancer (CRC). Nevertheless, the clinical benefit of statins, the inhibitor of cholesterol biogenesis mevalonate (MVA) pathway, is inconclusive, possibly because of a lack of patient stratification criteria. Here, we describe that YAP-mediated zinc finger MYND-type containing 8 (ZMYND8) expression sensitizes intestinal tumors to the inhibition of the MVA pathway. We show that the oncogenic activity of YAP relies largely on ZMYND8 to enhance intracellular de novo cholesterol biogenesis. Disruption of the ZMYND8-dependent MVA pathway greatly restricts the self-renewal capacity of Lgr5+ intestinal stem cells (ISCs) and intestinal tumorigenesis. Mechanistically, ZMYND8 and SREBP2 drive the enhancer-promoter interaction to facilitate the recruitment of Mediator complex, thus upregulating MVA pathway genes. Together, our results establish that the epigenetic reader ZMYND8 endows YAP-high intestinal cancer with metabolic vulnerability.

A critical time window for leukapheresis product transportation to manufacture clinical-grade dendritic cells with optimal anti-tumor activities.

BACKGROUND AIMS: Dendritic cell (DC)-based immunotherapy is a promising approach to treat cancer. However, key aspects governing the reproducible manufacturing of high-quality DC remain incompletely defined. Here, we show that the time window between leukapheresis and DC manufacturing is critical. METHODS: Transcriptomic profiling by RNA-seq was used to unbiasedly characterize cellular states during each step of DC manufacturing process, and functional assays were used to determine the anti-tumor activities of DC. RESULTS: During preclinical development of a DC-based cytotherapy platform, CUD-002 (NCT05270720), we found that DC quality varied among different batches, even though commonly used DC maturation markers CD80, CD83 and CD86 were indistinguishable. Multivariate analysis indicated that DC quality was negatively associated with the shipping time from the leukapheresis site to the manufacturing center. To investigate the potential effect of shipping time, we stored leukapheresis materials from three donors for 0, 1, 2 or 3 days before DC manufacturing. For each step, we carried out RNA-seq analysis to unbiasedly characterize cellular states. Integrated bioinformatic analyses indicated that longer storage time reduced the expression of several transcription factors to attenuate interferon pathways. CONCLUSIONS: Consistently, we found that 3-day storage of leukapheresis materials significantly lowered the efficiency to generate DC but also impaired DC responses to inflammatory signals, resulting in inferior antigen-presentation and cytotoxic T-cell activities. Thus, we recommend using leukapheresis materials within 48 h to manufacture therapeutic DCs.

Spokewise Total Syntheses of Four Erythrina Alkaloids and Telescoped Syntheses of Six Additional Alkaloids.

Based on rich sulfur-involving chemical transformations, a novel spokewise synthetic strategy, a subclass of the collective strategies, has been developed to concisely synthesize four erythrina alkaloids through a single-step transformation from a common synthetic precursor. Moreover, six additional erythrina alkaloids have also been synthesized by subsequent 1-2 steps chemical transformations. The current synthetic approaches provide a valuable platform for collective total syntheses of erythrina alkaloids and pseudo-natural erythrina alkaloids.

Comammox Nitrospira was the dominant ammonia oxidizer in an acidic biofilm reactor at pH 5.5 and pH 5.

Nitrification is a vital process in the biological removal of inorganic nitrogen compounds. In order to ensure the stability and effectiveness of this process, buffer solutions should be added to the system to maintain neutral to slightly alkaline conditions. With a focus on the newly discovered comammox Nitrospira, this research investigates the transition of the nitrifying community within a biofilm reactor under different acidic levels (initiated at pH 6 and gradually decreased to pH 5). During the 305-day continuous operation experiment, it was observed that responsible ammonia oxidizers transitioned from ammonia-oxidizing bacteria (AOB) during the initial stages (setup stage and early stage of pH 6) to comammox Nitrospira under pH 5.5 and pH 5. Further analysis using next-generation sequencing targeting both the 16S rRNA region and amoA region revealed a shift in the dominant cluster of both Nitrospirae and comammox Nitrospira under varying pH conditions. Our study identified a distinct cluster of comammox Nitrospira that is phylogenetically closed to sequences found in acidic environments, but exhibits dissimilarity from known comammox Nitrospira isolates and the majority of environmental sequences. This cluster was found to be prevalent in the acidic biofilm reactor studied and thrived particularly well at pH 5. These findings underscore the potential significance of this distinct, uncultivated group of comammox Nitrospira in performing ammonia oxidation under acidic conditions. KEY POINTS: • Ammonia was effectively removed under pH 5.5 and 5 in the biofilm reactor • The dominant ammonia oxidizer was comammox Nitrospira when pH was 5.5 and 5 • A potential acidophilic cluster of comammox Nitrospira was identified in this acidic biofilm reactor.

Biosurfactant production by Bacillus cereus GX7 utilizing organic waste and its application in the remediation of hydrocarbon-contaminated environments.

The use of biosurfactants represents a promising technology for remediating hydrocarbon pollution in the environment. This study evaluated a highly effective biosurfactant strain-Bacillus cereus GX7's ability to produce biosurfactants from industrial and agriculture organic wastes. Bacillus cereus GX7 showed poor utilization capacity for oil soluble organic waste but effectively utilized of water- soluble organic wastes such as starch hydrolysate and wheat bran juice as carbon sources to enhance biosurfactant production. This led to significant improvements in surface tension and emulsification index. Corn steep liquor was also effective as a nitrogen source for Bacillus cereus GX7 in biosurfactant production. The biosurfactants produced by strain Bacillus cereus GX7 demonstrated a remediation effect on oily beach sand, but are slightly inferior to chemical surfactants. Inoculation with Bacillus cereus GX7 (70.36%) or its fermentation solution (94.38%) effectively enhanced the degradation efficiency of diesel oil in polluted seawater, surpassing that of indigenous degrading bacteria treatments (57.62%). Moreover, inoculation with Bacillus cereus GX7's fermentation solution notably improved the community structure by increasing the abundance of functional bacteria such as Pseudomonas and Stenotrophomonas in seawater. These findings suggest that the Bacillus cereus GX7 as a promising candidate for bioremediation of petroleum hydrocarbons.

Diagnostic value of core needle biopsy for determining HER2 status in breast cancer, especially in the HER2-low population.

PURPOSE: The status of human epidermal growth factor receptor 2 (HER2) is important for treatment decision-making of breast cancer and was commonly determined by core needle biopsy (CNB). The concordance of CNB with surgical excision biopsy (SEB) has been verified, but remain unclear according to the newly developed classification of HER2 status. Our study aimed to re-evaluate the diagnostic value of CNB for determining HER2 status in breast cancer, especially in the HER2-low population. METHODS: Eligible breast cancer patients in West China Hospital between January 1, 2007 and December 31, 2021 were enrolled consecutively and data were extracted from the Hospital Information System. The agreement of HER2 status between CNB and SEB was calculated by concordance rate and κ statistics, as well as the sensitivity, specificity, positive, and negative predictive values (PPV & NPV). Logistic models were used to explore potential factors associated with the discordance between both tests. RESULTS: Of 1829 eligible patients, 1097 (60.0%) and 1358 (74.2%) were consistent between CNB and SEB by pathological and clinical classifications, respectively, with κ value being 0.46 (0.43-0.49) and 0.57 (0.53-0.60). The sensitivity (50.9%-52.7%) and PPV (50.5%-55.2%) of CNB were especially low among IHC 1+ and 2+/ISH - subgroups by pathological classifications; however, it showed the highest sensitivity (77.5%) and the lowest specificity (73.9%) in HER2-low population by clinical classifications. Advanced N stages might be a stable indicator for the discordance between both tests. CONCLUSION: The diagnostic value of CNB was limited for determining HER2 status in breast cancer, especially in HER2-low population.

Development of a personalized dendritic cell vaccine and single-cell RNA sequencing-guided assessment of its cell type composition.

BACKGROUND AIMS: Dendritic cell (DC)-based immunotherapy is a promising approach to treat cancer; however, there is no consensus on the manufacturing processes. Cell type heterogeneity in products manufactured by various methods is understudied and may elicit safety concerns from the regulatory perspective. METHODS: We characterized the cell type composition of a recently developed DC vaccine, CUD-002, consisting of DCs loaded with mRNA encoding personalized tumor neoantigens (NCT05270720). RESULTS: Using single-cell transcriptomic analysis as an unbiased approach, we found that >80% cells in the final product were DCs and the rest primarily comprised myelocytes and lymphocytes. Subsequent fluorescence-activated cell sorting analyses confirmed these cellular identities. These results indicate that unintended cells originate from leukapheresis, the first step of the manufacturing process, and thus likely safe. Consistently, no overt toxicity or tumorigenicity was observed in mice inoculated with CUD-002. CONCLUSIONS: Considering that leukapheresis is a widely used procedure for collecting diverse peripheral blood cell types to manufacture various cytotherapies, this study establishes a workflow to analyze and address regulatory considerations on cell type heterogeneity.

Comprehensive Multiomics Analysis of Monozygotic Twin Discordant for Double Outlet Right Ventricle.

The objective of this study was to understand and measure epigenetic changes associated with the occurrence of CHDs by utilizing the discordant monozygotic twin model. A unique set of monozygotic twins discordant for double-outlet right ventricles (DORVs) was used for this multiomics study. The cardiac and muscle tissue samples from the twins were subjected to whole genome sequencing, whole genome bisulfite sequencing, RNA-sequencing and liquid chromatography-tandem mass spectrometry analysis. Sporadic DORV cases and control fetuses were used for validation. Global hypomethylation status was observed in heart tissue samples from the affected twins. Among 36,228 differentially methylated regions (DMRs), 1097 DMRs involving 1039 genes were located in promoter regions. A total of 419 genes, and lncRNA-mRNA pairs involved 30 genes, and 62 proteins were significantly differentially expressed. Multiple omics integrative analysis revealed that five genes, including BGN, COL1A1, COL3A1, FBLN5, and FLAN, and three pathways, including ECM-receptor interaction, focal adhesion and TGF-ß signaling pathway, exhibited differences at all three levels. This study demonstrates a multiomics profile of discordant twins and explores the possible mechanism of DORV development. Global hypomethylation might be associated with the risk of CHDs. Specific genes and specific pathways, particularly those involving ECM-receptor interaction, focal adhesion and TGF-ß signaling, might be involved in the occurrence of CHDs.

A nomogram for predicting breast cancer specific survival in elderly patients with breast cancer: a SEER population-based analysis.

BACKGROUND: The number of elderly patients diagnosed with breast cancer is increasing worldwide. However, treatment decisions for these patients are highly variable. Although researchers have identified the effects of surgery, radiotherapy, endocrine therapy, and chemotherapy in elderly patients with breast cancer, clinicians still struggle to make appropriate decisions for these patients. METHODS: We identified 75,525 female breast cancer patients aged ≥ 70 years in the Surveillance, Epidemiology, and End Results (SEER) database treated between January 1, 2010, and December 31, 2016. The patients were further divided into training and testing cohorts. The cumulative occurrence of breast cancer-specific deaths (BCSDs) and other cause-specific deaths (OCSD) was calculated using the cumulative incidence function. In the univariate analysis, risk factors were screened using the Fine-Gray model. In the multivariate analysis for competing risks, the sub-distribution hazard ratio with a 95% confidence interval for each independent predictor associated with BCSD was calculated for the construction of nomograms. Based on the above analyses, a competing risk nomogram was constructed to predict the probability of BCSD in the 1st, 3rd, and 5th years after treatment. During validation, the concordance index (C-index) was selected to quantify the predictive ability of the competing risk model. RESULTS: A total of 33,118 patients were included in this study, with 24,838 in the training group and 8,280 in the testing group. Age, race, marital status, cancer grade, tumor stage, node stage, estrogen receptor status, progesterone receptor status, human epidermal growth factor receptor--2 status, and treatment including surgery, radiation, and chemotherapy were used to establish a nomogram. The C-index of 0.852 (0.842-0.862) in the training cohort and 0.876 (0.868-0.892) in the testing cohort indicated satisfactory discriminative ability of the nomogram. Calibration plots showed favorable consistency between the nomogram predictions and actual observations in both the training and validation cohorts. CONCLUSIONS: Our study identified independent predictors of BCSD in elderly patients with breast cancer. A prognostic nomogram was developed and validated to aid clinical decision-making.

Bioaugmentation enhance the bioremediation of marine crude oil pollution: Microbial communities and metabolic pathways.

Bioaugmentation is an effective strategy used to speed up the bioremediation of marine oil spills. In the present study, a highly efficient petroleum degrading bacterium (Pseudomonas aeruginosa ZS1) was applied to the bioremediation of simulated crude oil pollution in different sampling sites in the South China Sea. The metabolic pathways of ZS1 to degrade crude oil, the temporal dynamics of the microbial community response to crude oil contamination, and the biofortification process were investigated. The results showed that the abundance and diversity of the microbial community decreased sharply after the occurrence of crude oil contamination. The best degradation rate of crude oil, which was achieved in the samples from the sampling site N3 after the addition of ZS1 bacteria, was 50.94% at 50 days. C13 alkanes were totally oxidized by ZS1 in the 50 days. The degradation rate of solid n-alkanes (C18-C20) was about 70%. Based on the whole genome sequencing and the metabolites analysis of ZS1, we found that ZS1 degraded n-alkanes through the terminal oxidation pathway and aromatic compounds through the catechol pathway. This study provides data support for further research on biodegradation pathways of crude oil and contributes to the subsequent development of more reasonable bioremediation strategies.

[Pregnancy Outcomes and Prognosis of Fetal Ventriculomegaly: A Retrospective Cohort Study].

Objective: To evaluate the pregnancy outcomes and neurodevelopment prognosis of subjects prenatally diagnosed with fetal ventriculomegaly (VM). Methods: All the subjects with VM diagnosed by ultrasound and were admitted and treated at West China Second Hospital, Sichuan University between March 2011 and September 2020 were retrospectively enrolled for a chohort study, while non-VM subjects of the same period were selected with a random number table to form the control group. Pregnancy outcomes of the two groups were compared, and the fetuses of both groups were followed up after birth for further assessment and comparison of their neurodevelopmental prognosis. Results: The live birth rate of the VM group was lower than that of the control group (77.63% [229/295] vs. 94.31% [265/281], P<0.001). Furthermore, the proportion of subjects that were transferred to NICU for monitoring and observation after birth was higher in the VM group than that of the control group (20.96% [48/229] vs. 4.53% [12/265], P<0.001). During the follow-up, it was found that the rate of neurodevelopmental abnormalities of the VM group was significantly higher than that of the control group (11.79% [27/229] vs. 1.90% [5/265], P<0.001). Moreover, neurodevelopmental abnormalities of VM fetuses were correlated to the following factors, the degree of VM ( P=0.010), intrauterine progression of VM ( P=0.024), and whether the postnatal cranial ultrasound result was suggestive of VM ( P=0.001). In addition, postnatal cranial ultrasound suggestive of VM was found to be an independent risk factor for neurodevelopmental abnormalities ( OR=9.434, 95% CI: 1.791-49.688, P=0.008). Conclusion: VM reduces the fetal live birth rate and may increase the risks of neurodevelopmental abnormalities after birth. All VM fetuses should be closely followed up for neurodevelopment status after birth, especially those with severe VM, intrauterine progression, and postnatal cranial ultrasound indicative of VM.

Dynamics of the prokaryotic and eukaryotic microbial community during a cyanobacterial bloom.

Toxic cyanobacterial blooms frequently develop in eutrophic freshwater bodies worldwide. Microcystis species produce microcystins (MCs) as a cyanotoxin. Certain bacteria that harbor the mlr gene cluster, especially mlrA, are capable of degrading MCs. However, MC-degrading bacteria may possess or lack mlr genes (mlr+ and mlr- genotypes, respectively). In this study, we investigated the genotype that predominantly contributes to biodegradation and cyanobacterial predator community structure with change in total MC concentration in an aquatic environment. The 2 genotypes coexisted but mlr+ predominated, as indicated by the negative correlation between mlrA gene copy abundance and total MC concentration. At the highest MC concentrations, predation pressure by Phyllopoda, Copepoda, and Monogononta (rotifers) was reduced; thus, MCs may be toxic to cyanobacterial predators. The results suggest that cooperation between MC-degrading bacteria and predators may reduce Microcystis abundance and MC concentration.

ATM inhibition induces synthetic lethality and enhances sensitivity of PTEN-deficient breast cancer cells to cisplatin.

PTEN deficiency often causes defects in DNA damage repair. Currently, effective therapies for breast cancer are lacking. ATM is an attractive target for cancer treatment. Previous studies suggested a synthetic lethality between PTEN and PARP. However, the synthetically lethal interaction between PTEN and ATM in breast cancer has not been reported. Moreover, the mechanism remains elusive. Here, using KU-60019, an ATM kinase inhibitor, we investigated ATM inhibition as a synthetically lethal strategy to target breast cancer cells with PTEN defects. We found that KU-60019 preferentially sensitizes PTEN-deficient MDA-MB-468 breast cancer cells to cisplatin, though it also slightly enhances sensitivity of PTEN wild-type breast cancer cells. The increased cytotoxic sensitivity is associated with apoptosis, as evidenced by flow cytometry and PARP cleavage. Additionally, the increase of DNA damage accumulation due to the decreased capability of DNA repair, as indicated by γ-H2AX and Rad51 foci, also contributed to this selective cytotoxicity. Mechanistically, compared with PTEN wild-type MDA-MB-231 cells, PTEN-deficient MDA-MB-468 cells have lower level of Rad51, higher ATM kinase activity, and display the elevated level of DNA damage. Moreover, these differences could be further enlarged by cisplatin. Our findings suggest that ATM is a promising target for PTEN-defective breast cancer.

Inhibition of nuclear factor-kappa B enhances the tumor growth of ovarian cancer cell line derived from a low-grade papillary serous carcinoma in p53-independent pathway.

BACKGROUND: NF-kB can function as an oncogene or tumor suppressor depending on cancer types. The role of NF-kB in low-grade serous ovarian cancer, however, has never been tested. We sought to elucidate the function of NF-kB in the low-grade serous ovarian cancer. METHODS: The ovarian cancer cell line, HOC-7, derived from a low-grade papillary serous carcinoma. Introduction of a dominant negative mutant, IkBαM, which resulted in decrease of NF-kB function in ovarian cancer cell lines. The transcription ability, tumorigenesis, cell proliferation and apoptosis were observed in derivative cell lines in comparison with parental cells. RESULTS: Western blot analysis indicated increased expression of the anti-apoptotic proteins Bcl-xL and reduced expression of the pro-apoptotic proteins Bax, Bad, and Bid in HOC-7/IĸBαM cell. Further investigations validate this conclusion in KRAS wildtype cell line SKOV3. Interesting, NF-kB can exert its pro-apoptotic effect by activating mitogen-activated protein kinase (MAPK) phosphorylation in SKOV3 ovarian cancer cell, whereas opposite changes detected in p-MEK in HOC-7 ovarian cancer cell, the same as some chemoresistant ovarian cancer cell lines. In vivo animal assay performed on BALB/athymic mice showed that injection of HOC-7 induced subcutaneous tumor growth, which was completely regressed within 7 weeks. In comparison, HOC-7/IĸBαM cells caused sustained tumor growth and abrogated tumor regression, suggesting that knock-down of NF-kB by IĸBαM promoted sustained tumor growth and delayed tumor regression in HOC-7 cells. CONCLUSION: Our results demonstrated that NF-kB may function as a tumor suppressor by facilitating regression of low grade ovarian serous carcinoma through activating pro-apoptotic pathways.

PKC phosphorylates HEXIM1 and regulates P-TEFb activity.

The positive transcription elongation factor b (P-TEFb) regulates RNA polymerase II elongation. In cells, P-TEFb partitions between small active and larger inactive states. In the latter, HEXIM1 binds to 7SK snRNA and recruits as well as inactivates P-TEFb in the 7SK snRNP. Several stimuli can affect this P-TEFb equilibrium. In this study, we demonstrate that protein kinase C (PKC) phosphorylates the serine at position158 (S158) in HEXIM1. This phosphorylated HEXIM1 protein neither binds to 7SK snRNA nor inhibits P-TEFb. Phorbol esters or the engagement of the T cell antigen receptor, which activate PKC and the expression of the constitutively active (CA) PKCθ protein, which is found in T cells, inhibit the formation of the 7SK snRNP. All these stimuli increase P-TEFb-dependent transcription. In contrast, the kinase-negative PKCθ and the mutant HEXIM1 (S158A) proteins block effects of these PKC-activating stimuli. These results indicate that the phosphorylation of HEXIM1 by PKC represents a major regulatory step of P-TEFb activity in cells.

Extra-cerebral recombination activity of Emx1-Cre and nestin-Cre in the kidney.

Individuals with neurodevelopmental disorders (NDDs) are frequently diagnosed with comorbidities in other organs, indicating that NDD risk genes may have extra-cerebral functions. The engineered mouse models are pivotal in understanding the functions of candidate NDD genes. Here, we report that Emx1-Cre and nestin-Cre mouse strains, the popular tools to study brain development, also exhibit recombination activity in the kidney. We find that both Emx1-Cre and nestin-Cre can drive recombination in epithelial cells lining proximal and distal convoluted tubules of the nephron. Additionally, nestin-Cre drives recombination in the glomerulus of the nephron. Furthermore, we use Emx1-Cre and nestin-Cre to knock out Larp7, a gene linked to a human NDD called Alazami syndrome. We find that Larp7 knockout using nestin-Cre, but not Emx1-Cre, results in elevated blood urea nitrogen. This result suggests a compromised kidney function, reminiscent of recently revealed renal anomalies in Alazami syndrome patients. Many genes have been knocked out using Emx1-Cre and nestin-Cre to study their roles during embryonic neurogenesis. It will be of great interest to reinvestigate whether the renal development and function is affected in these existing mouse models.

A new subtype of Lynch syndrome associated with MSH2 c.354T>A (p. Y118*) identified in a Chinese family: case report and literature review.

Background: Lynch syndrome (LS) is an autosomal dominant inherited disorder caused by mutations in mismatch repair genes. Genetic counseling is crucial for the prevention and treatment of LS, as individuals with these mutations have an increased lifetime risk of developing multiple cancers. MutS Homolog 2 (MSH2) is a protein-coding gene that plays a key role in LS. A significant number of LS cases are linked to harmful heterozygous mutations in the MSH2 gene. Case Presentation: The proband was a 50-year-old endometrial dedifferentiated carcinoma patient with a dMMR/MSI-H tumor negative for MSH2/MSH6 expression by immunohistochemistry. Genetic counseling and tumor gene testing were conducted using next-generation sequencing (NGS) technology, which revealed a previously unknown germline MSH2 gene nonsense mutation NM_000251.2:exon2.354T>A (p.Y118*), leading to a diagnosis of LS. Further analysis of this variant in five family members of the patient confirmed its presence in all individuals, with one family member being diagnosed with colorectal cancer (CRC) at the age of 43. The proband received postoperative chemoradiotherapy and achieved a disease-free survival of 2 years, with ongoing follow-up. Conclusion: This study provides evidence that the MSH2 nonsense mutation c.354T>A is a highly likely pathogenic mutation and is responsible for typical LS-associated endometrial carcinoma. It emphasizes the importance of genetic counseling for proband family members to facilitate early diagnosis of LS-related carcinoma.

PARP inhibitor maintenance treatment for newly diagnosed ovarian cancer patients: a real-world study from China.

Purpose: This study evaluated the efficacy and safety in a real-world population of epithelial ovarian cancer (EOC) treated with poly (ADP-ribose) polymerase inhibitor (PARPi) as first-line maintenance therapy in the largest gynecologic oncology center in Western China. Methods: This study included patients newly diagnosed EOC who received PARPi as first-line maintenance therapy in West China Second University Hospital from August 1, 2018 to September 31, 2022. The primary endpoints were progression-free survival (PFS) and safety evaluated by Common Terminology Criteria for Adverse Events Version 5.0(CTCAE 5.0). The secondary endpoints were overall survival (OS) and prognostic factors influencing the PFS of patients in real world. Results: Among the eligible 164 patients, 104 patients received olaparib and 60 patients received niraparib. 100 patients (61.0%) had mutations in breast cancer susceptibility gene (BRCA). 87 patients (53.0%) received primary debulking surgery (PDS) while 77 patients (47.0%) received interval debulking surgery (IDS). 94 patients (94/164, 57.3%) achieved R0 and 39 patients (23.8%) achieved R1 after PDS/IDS. 112 (68.3%) achieved complete response (CR) after first-line chemotherapy, while 49 (29.9%) achieved partial response (PR). The median follow-up time was 17.0 months (95% CI 15.6-18.4), and the median PFS has not been reached yet. Multivariate analysis demonstrated that BRCA mutations and CR/PR after platinum-based chemotherapy were independent factors associated with prolonged PFS. Hematologic toxicity was the most common grade≥3 AE. There were no incidence of myelodysplastic syndromes/acute myelogenous leukemia (MDS/AML). Conclusion: Focusing on PARPi as first-line maintenance therapy for patients with EOC, this study represented the largest single-center real-world study in China to date. Two independent factors were identified to prolong the PFS of patients: BRCA mutated type and CR/PR after primary treatment, which should be further confirmed with long-term follow-up and large sample sizes.

Corrigendum: Therapeutic strategies targeting folate receptor α for ovarian cancer.

[This corrects the article DOI: 10.3389/fimmu.2023.1254532.].