P4HA2-mediated HIF-1α stabilization promotes erdafitinib-resistance in FGFR3-alteration bladder cancer.

Erdafitinib is a novel fibroblast growth factor receptor (FGFR) inhibitor that has shown great therapeutic promise for solid tumor patients with FGFR3 alterations, especially in urothelial carcinoma. However, the mechanisms of resistance to FGFR inhibitors remain poorly understood. In this study, we found Erdafitinib could kill cells by inducing incomplete autophagy and increasing intracellular reactive oxygen species levels. We have established an Erdafitinib-resistant cell line, RT-112-RS. whole transcriptome RNA sequencing (RNA-Seq) and Cytospace analysis performed on Erdafitinib-resistant RT-112-RS cells and parental RT-112 cells introduced P4HA2 as a linchpin to Erdafitinib resistance. The gain and loss of function study provided evidence for P4HA2 conferring such resistance in RT-112 cells. Furthermore, P4HA2 could stabilize the HIF-1α protein which then activated downstream target genes to reduce reactive oxygen species levels in bladder cancer. In turn, HIF-1α could directly bind to P4HA2 promoter, indicating a positive loop between P4HA2 and HIF-1α in bladder cancer. These results suggest a substantial role of P4HA2 in mediating acquired resistance to Erdafitinib and provide a potential target for bladder cancer treatment.

Establishment and validation of a predictive model of preeclampsia based on transcriptional signatures of 43 genes in decidua basalis and peripheral blood.

Preeclampsia (PE) has an increasing incidence worldwide, and there is no gold standard for prediction. Recent progress has shown that abnormal decidualization and impaired vascular remodeling are essential to PE pathogenesis. Therefore, it is of great significance to analyze the decidua basalis and blood changes of PE to explore new methods. Here, we performed weighted gene co-expression network analysis based on 9553 differentially expressed genes of decidua basalis data (GSE60438 includes 25 cases of PE and 23 non-cases) from Gene Expression Omnibus to screen relevant module-eigengenes (MEs). Among them, MEblue and MEgrey are the most correlated with PE, which contains 371 core genes. Subsequently, we applied the logistic least absolute shrinkage and selection operator regression, screened 43 genes most relevant to prediction from the intersections of the 371 genes and training set (GSE48424 includes 18 cases of PE and 18 non-cases) genes, and built a predictive model. The specificity and sensitivity are illustrated by receiver operating characteristic curves, and the stability was verified by two validation sets (GSE86200 includes 12 cases of PE and 48 non-cases, and GSE85307 includes 47 cases of PE and 110 non-cases). The results demonstrated that our predictive model shows good predictions, with an area under the curve of 0.991 for the training set, 0.874 and 0.986 for the validation sets. Finally, we found the 43 key marker genes in the model are closely associated with the clinically accepted predictive molecules, including FLT1, PIGF, ENG and VEGF. Therefore, this predictive model provides a potential approach for PE diagnosis and treatment.

CEMIP promotes extracellular matrix-detached prostate cancer cell survival by inhibiting ferroptosis.

Cells detached from the extracellular matrix (ECM) can trigger different modes of cell death, and the survival of ECM-detached cells is one of the prerequisites for the metastatic cascade. Ferroptosis, a form of iron-dependent programmed cell death, has recently been found to be involved in matrix-detached cancer cells. However, the molecular mechanisms by which ECM-detached cells escape ferroptosis are not fully understood. Here, we observed that cell migration-inducing protein (CEMIP) upregulation facilitates ferroptosis resistance during ECM detachment by promoting cystine uptake in prostate cancer (PCa) cells. Meanwhile, silencing CEMIP causes it to lose its ability to promote cystine uptake and inhibit ferroptosis. Mechanistically, the interaction of CEMIP with inositol 1,4,5-trisphosphate receptor type 3 (ITPR3) modulates calcium ion (Ca2+ ) leakage from the endoplasmic reticulum, activating calcium/calmodulin-dependent protein kinase II (CaMKII), which further facilitates nuclear factor erythroid 2-related factor 2 (NRF2) phosphorylation and nuclear localization, leading to elevated transcription of solute carrier family 7 member 11 (SLC7A11), a glutamate/cystine antiporter, in PCa cells. Our findings delineate a novel role of CEMIP in ferroptosis resistance during ECM detachment and provide new insights into therapeutic strategies for metastatic PCa.

Atomically Dispersed Cu Catalyst for Efficient Chemoselective Hydrogenation Reaction.

The Cu-based nanocatalysts have shown a high selectivity toward selective hydrogenation reaction, but the underlying catalytic mechanism is still murky. Herein, we report a new gram-scale strategy for realizing the single atom Cu site incorporated into the melem ring of graphitic carbon nitride (Cu1/CN) for understanding the catalytic mechanism of a hydrogenation reaction. The as-synthesized Cu1/CN exhibits unprecedented selectivity (100%), high activity (TOF = 2.9 × 103 h-1), and outstanding stability for selective hydrogenation of 4-nitrostyrene. We reveal that the presence of hydroxymethyl from trimethylolmelamine is beneficial to atomically disperse Cu atoms in the CN. X-ray absorption fine structure tests reveal that the Cu atom of Cu1/CN is dominated by the quaternary coordination way (Cu-N4) in the melem ring of CN. Density functional theory calculations confirm that the high reactivity and selectivity originate from the anchored Cu sites creating the optimal chemical environment for the highly efficient hydrogenation reaction.

Overexpression of GAS5 inhibits abnormal activation of Wnt/ß-catenin signaling pathway in myocardial tissues of rats with coronary artery disease.

OBJECTIVE: The aim of this study is to investigate the clinical value of long noncoding RNA growth arrest-specific transcript 5 (LncRNA GAS5) in the diagnosis of coronary artery disease (CAD) and its protective effect on myocardial injury in rats with CAD. METHODS: Patients with CAD and healthy controls were selected to measure the expression of GAS5, and further to perform the correlation analysis and ROC curve. In addition, the rat models of CAD were also established to observe the effect of GAS5 on hyperlipidemia, myocardial injury, cardiomyocyte apoptosis, oxidative stress, and inflammatory injury of rats with CAD, and the effect of the Wnt/ß-catenin signaling pathway was also determined. RESULTS: Overexpression of GAS5 in CAD rats determines improvement of hyperlipidemia, attenuation of myocardial injury, inhibition of cardiomyocyte apoptosis, oxidative stress, inflammatory injury, and abnormal activation of the Wnt/ß-catenin signaling pathway in myocardial tissues. CONCLUSION: Our study demonstrates that downregulation of GAS5 is found in CAD, and overexpression of GAS5 inhibits abnormal activation of the Wnt/ß-catenin signaling pathway in myocardial tissues of CAD rats.

DJ-1 as a potential biomarker for the early diagnosis in lung cancer patients.

DJ-1 is a novel oncogene that can transform NIH3T3 cells in cooperation with the activated ras gene. DJ-1 appears to have its greatest effect on tumourigenesis, and it may have a greater impact on early-stage lung cancers. In this study, we proposed to investigate the clinical value of DJ-1 protein in the early diagnosis of lung cancer and compared its diagnostic value with other biomarkers. Preoperative serum DJ-1 levels were measured in 300 lung cancer patients and compared with benign pulmonary disease (n = 44) and healthy volunteers (n = 64). Using tissue microarrays and immunohistochemical analyses, we compared the DJ-1 expression between the primary squamous cell carcinoma tumours and matched metastatic tissues from a lymph node. The baseline preoperative serum DJ-1 of lung cancer patients was significantly higher than that of benign diseases and healthy controls (p < 0.001). In the early-stage subgroup, the median DJ-1 concentration (ng/mL) was significantly higher than that of the advanced stage (12.90 vs 7.75, p < 0.05). Using immunohistochemistry, we observed that the DJ-1 staining intensity was generally weaker and less common in the metastatic tissues compared with that in the primary tumour (McNemar-Bowker Test, p = 0.008). DJ-1 was highly expressed in the early stage of lung cancer, and its expression was significantly decreased after metastasis. Therefore, DJ-1 may be a potential biomarker for the early diagnosis and monitoring of lung cancer metastasis.

Dissecting Trichalcogenasumanenes: π-Bowl to Planar, Invertible Curvature, and Chiral Polycycles.

The buckybowl trichalcogenasumanenes show cleavage of flanking benzene ring upon oxidation, which leads their dissection by fusing various amidine moieties onto peripheral region. By gradually increasing the ring size of amidine from five- to six- and seven-membered, the molecule engineering results in the [7-5-6]-, [7-6-6]-, and [7-7-6]-fused polycycles. Three systems are distinct in the molecular geometries, packing motifs, and optoelectronic properties. The [7-5-6]-fused case adopts the flat backbone, displays strong emission with the fluorescence quantum yield up to 52.3 %, and undergoes a two-photon absorption process. The [7-6-6]-fused one is of a curvature with molecular geometry inversion, forms a tight stack of curved π-system, shows broad absorption extended to 700 nm, and exhibits the p-type semiconducting behavior with hole mobility of 4.4×10-3  cm2 V-1 s-1 . The [7-7-6]-fused one possesses the highly twisted skeleton to show stable chirality, and exhibits red emission in both solution and solid state. The surgery on trichalcogenasumanene is a promising approach to create polycycles with diverse functionalities.

Prognostic Factors for In-Hospital and Long-Term Survival in Patients with Acute ST-Segment Elevation Myocardial Infarction after Percutaneous Coronary Intervention.

Acute ST segment elevation myocardial infarction (STEMI) is one of the causes of death and disability in patients with cardiovascular diseases. This study aimed to investigate the prognostic factors of in-hospital and long-term survival in patients with acute STEMI undergoing percutaneous coronary intervention (PCI). Patients with STEMI undergoing PCI were divided into the death group (n = 54) and the survival group (n = 306) based on the outcomes during hospitalization. The routine blood and biochemistry tests, Killip classes and global registry of acute coronary events (GRACE) risk score were detected. The 1-, 2- and 3-year survival rates after PCI was observed through a 3-year follow-up. The survival factors, survival rates and multivariate analyses were conducted using Logistic regression analysis, Kaplan-Meier survival analysis and Cox proportional hazards regression. The incidence of cardiogenic shock and anterior wall MI (AWMI), the serum levels of γ-glutamyl endopeptidase (γ-GGT) and creatine kinase isoenzyme MB (CK-MB), Killip classes and GRACE risk score were higher in the death group, compared with the survival group. AWMI, cardiogenic shock, high serum levels of γ-GGT and CK-MB, Killip class III-IV and high GRACE risk scores were associated with in-hospital mortality. AWMI, cardiogenic shock, Killip class III-IV and high GRACE risk scores were correlated with a poor long-term survival. Our findings have demonstrated that AWMI, cardiogenic shock, high serum levels of γ-GGT and CK-MB, Killip class III-IV, and high GRACE risk scores are risk factors for in-hospital and long-term prognosis of acute STEMI patients.

Trichalcogenasumanene ortho-Quinones: Synthesis, Properties, and Transformation into Various Heteropolycycles.

The regioselective transformation of heterobuckybowl trichalcogenasumanenes 1 a,b at peripheral butoxy groups afforded trichalcogenasumanene ortho-quinones 2 a,b. Compounds 2 a,b are distinct from 1 a,b in terms of their molecular geometry and electronic state; that is, they have a shallower bowl depth and show absorbance in the NIR region. The reaction of 2 a,b with diamines resulted in a variety of heteropolycycles, including molecular spoon 3 a-6 a, planar π-systems 3 b-6 b, and highly twisted [7-6-6]-fused systems 7 a,b. These new heteropolycycles had different optical/electrical properties: 4 a,b showed hole mobility of approximately 0.002 cm2 V-1 s-1 , 6 a displayed red emission in both solution and the solid state, and 7 a,b formed tight stacks of the curved π-surface.

Ring reconstruction on a trichalcogenasumanene buckybowl: a facile approach to donor-acceptor-type [5-6-7] fused planar polyheterocycles.

The transformation of trichalcogenasumanene buckybowls into donor-acceptor-type [5-6-7] fused polyheterocycles is disclosed. The strategy involves a highly efficient ring-opening of the flanking benzene upon oxidation at room temperature, and facile ring closure by functional-group transformation. Crystallographic studies indicate that the resulting [5-6-7] fused polyheterocycles possess a planar conformation owing to the release of ring strain by expansion of one of the six-membered flanking rings to the seven-membered one. Additionally, the [5-6-7] fused polyheterocycles bear electron-withdrawing groups, which reduce the HOMO-LUMO energy gap, and display broad absorption bands extending to λ=590 nm. Consequently, these compounds show strong red emission with fluorescence quantum yields of up to 38 %.

Non-pyrolytic, large-scale synthesis of trichalcogenasumanene: a two-step approach.

Trichalcogenasumanenes were synthesized on a multigram scale through a two-step approach that takes advantage of non-pyrolytic cyclization and solventless ring contraction. Solid-state structure and photophysical investigations demonstrate that these compounds are promising candidates for electronic materials.

Molecular and crystal structure diversity, and physical properties of tetrathiafulvalene derivatives substituted with various aryl groups through sulfur bridges.

A library of tetrathiafulvalene (TTF) derivatives (TTF-1-TTF-47) bearing aryl groups attached through sulfur bridges has been created. The peripheral aryl groups exert a significant influence on both the electronic and crystallographic properties of the resulting TTFs. These TTFs display broad absorption bands at 400-500 nm caused by intramolecular charge-transfer transitions between the aryl groups and central TTF core, and their first redox potentials increase with increasing electron-withdrawing ability of the aryl groups. In their crystal structures (22 examples), the central TTF cores adopt various conformations, including chair, half-chair, boat, and planar conformations. Moreover, the peripheral aryl groups exhibit multiple alignment modes with respect to the central TTF core, caused by their rotation about the two C-S bonds of the sulfur bridges. The packing motifs of these TTFs depend on both the nature of the aryl groups and their spatial alignment modes. Driven by intermolecular van der Waals forces and π-π interactions between the aryl groups and between the aryl groups and the TTF core, these TTFs adopt various packing structures. As a typical example, TTF-14, an achiral molecule, adopts a helical chain stack through intermolecular atomic close contacts. Moreover, the molecular geometries and packing motifs of these TTFs are sensitive to environmental variation, as exemplified by TTF-28, which adopts three distinct crystal modifications with diverse molecular geometries and stacking modes under different crystallization conditions. This work indicates that these TTFs are potential candidates as electronic materials, as well as functional building blocks for supramolecular assembly.

A straightforward synthesis and physicochemical properties of chiral phosphorus-doped coronenes.

Novel N,P-fused coronene derivatives have been successfully designed and achieved in one step using a three-fold Bischler-Napieralski cyclization as the key step. The unique structure, and tunable photophysical and electronic properties make them promising candidates for emissive and electron-transport materials.

SGK2 promotes prostate cancer metastasis by inhibiting ferroptosis via upregulating GPX4.

Recent research has shown that ferroptosis, the iron-dependent accumulation of lipid peroxides that leads to cell death, suppresses cancer metastasis. However, the role of ferroptosis in prostate cancer metastasis has not been completely elucidated. In the current study, we identified the essential role of serum/glucocorticoid regulated kinase 2 (SGK2) in promoting prostate cancer metastasis by inhibiting ferroptosis. We found that the expression of SGK2 was higher in metastatic prostate cancer and predicted poor clinical outcomes. SGK2 knockdown inhibited the metastatic capacity of prostate cancer cells in vivo and in vitro, while SGK2 overexpression inhibited ferroptosis and facilitated prostate cancer metastasis by phosphorylating the Thr-24 and Ser-319 sites of forkhead box O1 (FOXO1). This process induced the translocation of FOXO1 from the nucleus to the cytoplasm, relieving the inhibitory effect of FOXO1 on glutathione peroxidase 4 (GPX4). These findings delineated a novel role of SGK2 in ferroptosis regulation of prostate cancer metastasis, identifying a new key pathway driving prostate cancer metastasis and potentially providing new treatment strategies for metastatic prostate cancer.

A systematic review and meta-analysis of efficacy and safety comparing holmium laser enucleation of the prostate with transurethral resection of the prostate for patients with prostate volume less than 100 mL or 100 g.

Background: To assess the efficacy and safety of holmium laser enucleation of the prostate (HoLEP) and transurethral resection of the prostate (TURP) for patients with prostate volume less than 100 mL or 100 g. Methods: We searched PubMed, Embase, Cochrane Library and Web of Science from inception to July 2021 to collect randomized controlled trials. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies by using the Cochrane risk of bias tool. Review Manager 5.3 software was used for meta-analysis. We synthesised effect estimates using risk ratios (RR), mean difference (MD), and standardized mean differences (SMD). Results: A total of eight studies were included, involving 764 patients, 384 patients in the HoLEP group and 380 patients in the TURP group. The meta-analysis showed that the catheterization time (SMD =-1.44; 95% CI: -2.17 to -0.70; P=0.0001), hospital stay (SMD =-1.01; 95% CI: -1.58 to -0.44; P=0.0005), haemoglobin loss (MD =-0.29; 95% CI: -0.52 to -0.07; P=0.01), and transfusion rate (RR =0.16; 95% CI: 0.05-0.49; P=0.001) in the HoLEP group were lower than those in the TURP group. In addition, the 12-month postvoid residual volume (PVR) of the HoLEP group (MD =-9.93 95% CI: -18.59 to -1.27; P=0.02) were superior to the TURP group. Although the operation time of the HoLEP group was longer (MD =17.89; 95% CI: 9.18-26.60; P<0.0001), more tissues were removed (SMD =0.47; 95% CI: 0.10-0.85; P=0.01). Discussion: Compared with TURP, HoLEP has a shorter catheterization time and hospital stay, with more tissue removed, a lower blood transfusion rate and better results in the short-term follow-up after surgery. Therefore, HoLEP has better efficacy and safety in the treatment of small- and medium-sized benign prostatic obstruction. Our results found that HoLEP is also suitable for patients with prostate volume <100 mL/100 g, suggesting that it is necessary to redefine the prostate size that is best for HoLEP. Overall, the certainty of evidence was assessed to be moderate to low due to potential risk of bias and inconsistent outcome indicators in some studies. More data on the efficacy of HoLEP and TURP on small- and medium-sized prostates are needed to determine the optimal prostate volume of HoLEP.

Circ_0004087 interaction with SND1 promotes docetaxel resistance in prostate cancer by boosting the mitosis error correction mechanism.

BACKGROUND: Acquisition of the chemoresistance to docetaxel (DTX), a microtubule-targeting agent, has been a huge obstacle in treatment for metastatic castration-resistant prostate cancer (mCRPC). Recently, strategies targeting the mitosis error correction mechanism including chromosomal passenger complex (CPC) were reported to reverse the resistance to microtubule-targeting anticancer agents. Meanwhile, accumulating evidence indicated the important roles of circRNAs in DTX resistance of prostate cancer (PCa). However, whether circRNAs could regulate DTX chemosensitivity by affecting the mitosis error correction mechanism remains unclear. METHODS: Expression patterns of circ_0004087 and BUB1 were determined through mining the public circRNA datasets and performing western blot and qRT-PCR assays. Agarose gel electrophoresis, Sanger sequencing, and RNase R treatment were conducted to examine the circular characteristics of circ_0004087. CircRNA pull-down, mass spectrometry analysis, Co-IP, and dual-luciferase reporter assays were performed to uncover the interaction among circ_0004087, SND1, and MYB. The effects of circ_0004087 and BUB1 on docetaxel-based chemotherapy were explored by flow cytometry and in vivo drug studies upon xenografted tumor model. RESULTS: In the present study, we revealed the profound interaction between a novel circRNA, circ_0004087, and the mitosis error correction mechanism. Mechanistically, circ_0004087 binding with transcriptional coactivator SND1 could stimulate the transactivation of MYB and enhance the expression of downstream target BUB1. In turn, elevated BUB1 expression further recruited CPC to centromeres and guaranteed the error-free mitosis of PCa cells. Biologically, the overexpression of circ_0004087 conferred while the knockdown impaired DTX resistance in PCa cells. CONCLUSIONS: Our study uncovered the crucial role of circ_0004087/SND1/MYB/BUB1 axis in modulating the error mitosis correction mechanism and DTX chemoresistance, suggesting that circ_0004087 may serve as a valuable prognostic biomarker and a potential therapeutic target in DTX-resistant PCa patients.

Carbon Sink Cost and Influence Factors Analysis in a National Afforestation Project under Different Investment Modes.

Afforestation projects are the main source of carbon sink. Measurement and impact analysis of carbon sink costs will help accelerate the marketization of forestry carbon sink. Considering the opportunity cost of land use and the carbon release cost of wood products, this study proposed a forestry carbon sink cost model under the Public-Private Partnership (PPP) and the direct (DI) investment mode based on the classic carbon sink model. Then, the proposed models were applied to a real-world afforestation project, the 20-year national afforestation project (NAP) in Laohekou City, Hubei Province, China. With the help of the input-output forestry carbon sink cost-benefit analysis framework, the dynamic analysis of factors such as rotation period, timber price, discount rate and yield rate for forestry is carried out. Results show that: (1) with the increasing of rotation period, wood market price, and wood yield rate, the carbon sink cost of Laohekou NAP gradually decreases, while the discount rate has the opposite trend; (2) the DI mode is more feasible than the PPP model at the present condition. The PPP mode is more feasible than the DI mode only when the wood price is lower than 73.18% of the current price, the yield rate is lower than 0.485, and the discount rate is higher than 6.77%. (3) When choosing tree species for NAP, the carbon sink capacity, wood market price, maturity time, and planting cost should be synthetically considered. The proposed model and the obtained results can not only support local governments and forestry carbon sink enterprises to make tradeoffs between PPP and DI mode, but also provide them with useful information for reducing carbon sink costs.

CircCEMIP promotes anoikis-resistance by enhancing protective autophagy in prostate cancer cells.

BACKGROUND: Circular RNAs (circRNAs) are essential participants in the development and progression of various malignant tumors. Previous studies have shown that cell migration-inducing protein (CEMIP) accelerates prostate cancer (PCa) anoikis resistance (AR) by activating autophagy. This study focused on the effect of circCEMIP on PCa metastasis. METHODS: This study gradually revealed the role of circ_0004585 in PCa anoikis resistance via quantitative real-time PCR (qRT-PCR) analysis, western blotting, pull-down assays, and dual fluorescence reporter assays. RESULTS: Functionally, circ_0004585 promoted PCa cells invasion and metastasis both in vitro and in vivo. Mechanistically, circ_0004585 directly interacted with miR-1248 to upregulate target gene expression. Furthermore, target prediction and dual-luciferase reporter assays identified transmembrane 9 superfamily member 4 (TM9SF4) as a potential miR-1248 target. Pathway analysis revealed that TM9SF4 activated autophagy to promote PCa cells anoikis resistance via mTOR phosphorylation. CONCLUSIONS: These results demonstrated that circ_0004585 played an oncogenic role during PCa invasion and metastasis by targeting the miR-1248/TM9SF4 axis while providing new insight into therapeutic strategy development for metastatic PCa.

ATF4/CEMIP/PKCα promotes anoikis resistance by enhancing protective autophagy in prostate cancer cells.

The survival of cancer cells after detaching from the extracellular matrix (ECM) is essential for the metastatic cascade. The programmed cell death after detachment is known as anoikis, acting as a metastasis barrier. However, the most aggressive cancer cells escape anoikis and other cell death patterns to initiate the metastatic cascade. This study revealed the role of cell migration-inducing protein (CEMIP) in autophagy modulation and anoikis resistance during ECM detachment. CEMIP amplification during ECM detachment resulted in protective autophagy induction via a mechanism dependent on the dissociation of the B-cell lymphoma-2 (Bcl-2)/Beclin1 complex. Additional investigation revealed that acting transcription factor 4 (ATF4) triggered CEMIP transcription and enhanced protein kinase C alpha (PKCα) membrane translocation, which regulated the serine70 phosphorylation of Bcl-2, while the subsequent dissociation of the Bcl-2/Beclin1 complex led to autophagy. Therefore, CEMIP antagonization attenuated metastasis formation in vivo. In conclusion, inhibiting CEMIP-mediated protective autophagy may provide a therapeutic strategy for metastatic prostate cancer (PCa). This study delineates a novel role of CEMIP in anoikis resistance and provides new insight into seeking therapeutic strategies for metastatic PCa.

[Diagnostic value of combining detection of human epididymis protein 4 and CA125 in patients with malignant ovarian carcinoma].

OBJECTIVE: To investigate the clinical value of combination of human epididymis protein 4 (HE4), CA125 and the Risk of Ovarian Malignancy Algorithm (ROMA) in diagnosis of ovarian carcinoma. METHODS: To detect the serum concentration of HE4 using ELISA and CA125 using ECL in patients of ovarian carcinoma group (n = 119), borderline ovarian tumor group (n = 36), benign ovarian neoplasm group (n = 96) and female healthy control group (n = 53). The ROMA based on the serum level of CA125, HE4 and a woman's menopausal status was used to calculate the predicted probability (PP) and diagnostic results of ovarian cancers. RESULTS: The receiver operating characteristic (ROC) analysis showed the cut-off value was 67.3 pmol/L (the AUC was 0.906, the sensitivity was 80.7% and specificity was 94.6%). The serum levels of HE4 and CA125 in the ovarian carcinoma group were significantly higher than that in the borderline ovarian tumor group, benign ovarian neoplasm group and female healthy control group (P < 0.01). The serum levels of CA125 and HE4 showed statistically no significant difference between the borderline ovarian tumor group and benign ovarian neoplasm group (P > 0.05). The levels of HE4 and CA125 were reduced significantly in ovarian patients after surgery therapy (P < 0.01). The sensitivity and specificity of HE4 + CA125 combination was 92.7% and 72.5%. The ROMA that can classify patients into high and low risk groups was established as 9.3% in premenopausal and 27.3% in postmenopausal women. CONCLUSIONS: HE4 is a helpful biomarker for ovarian carcinoma diagnosis. Biomarker combination of HE4 and CA125, and applying of the ROMA are helpful to improve the accuracy in diagnosis of ovarian cancers.