Sulfur enhances iron plaque formation and stress resistance to reduce the transfer of Cd and As in the soil-rice system.

Sulfur plays an essential role in agricultural production, but few studies have been reported on how sulfur simultaneously impacts the transformation of cadmium (Cd) and arsenic (As) in the soil-rice system. This research selected two soils co-contaminated with both Cd and As, varying in acidity and alkalinity levels, to study the impacts of elemental sulfur (S) and calcium sulfate (CaSO4) on the migration and accumulation of Cd and As by rice. Results indicated that two types of sulfur had a substantial (P < 0.05) impact on decreasing the contents of Cd (28.3-50.4 %) and As (20.1-38.6 %) in brown rice in acidic and alkaline soils. They also increased rice biomass (29.3-112.8 %) and reduced Cd transport coefficient (27.2-45.6 %) significantly (P < 0.05). Notably, sulfur augmented the generation of iron plaque on rice root surfaces, which increased the fixation of Cd (17.6-61.0 %) and As (14.0-45.9 %). SEM-EDS results also indicated that the rice root surface exhibited significant enrichment of Fe, Cd, and As. The mechanism of simultaneous Cd and As immobilization by sulfur application was mainly ascribed to the contribution of iron plaque. Additionally, sulfur reduced the contents of Cd and As in soil porewater and promoted the transformation of As(III) to As(V) to reduce the toxicity of As. The K-edge XAFS of As in iron plaque also confirmed that sulfur application significantly promoted As(III) oxidation. Sulfur also promoted the activities of antioxidant enzymes and the contents of NPT, GSH, and PCs in rice plants. In general, this study establishes a foundation for sulfur to lower As and Cd bioavailability in paddy soils, enhance iron plaque and rice resistance, and reduce heavy metal accumulation.

Full-face ALA-PDT for facial actinic keratosis: Two case reports.

We reported two cases of full-face 5-aminolevulinic acid-photodynamic therapy (ALA-PDT) for facial multiple actinic keratosis (AK). After the full-face ALA-PDT, we observed that the AK lesions on the faces of the patients were completely cleared and facial rejuvenation was achieved. In our follow-up, one patient was free of recurrence for over 13 months and the other one for over 28 months. The experience of these two cases may indicate that full-face ALA-PDT has an excellent therapeutic effect while potentially preventing the recurrence of AK.

Sclerosing Angiomatoid Nodular Transformation of the Spleen: Radiological Findings and Radiological-pathological Correlation

Introduction: The objective of this study was to describe the CT and MRI features of sclerosing angiomatoid nodular transformation (SANT) of the spleen with pathologic correlation. Materials and Methods: Ten patients with surgically resected and pathologically confirmed SANTs were included. Clinical history was reviewed, and gross pathologic, histologic, and immunohistochemical findings were recorded. CT and MRI examinations were evaluated by two radiologists. Results: Patients included seven men and three women, with a mean age of 42.9±16.7 years. Pathologic features of SANTs involved multiple angiomatous nodules in a radiating pattern with a central stellate fibrous scar and evidence of hemosiderin deposition. 9 cases showed a lobulated demarcated margin, 8 cases a slight hypoattenuating, 1 isoattenuating, and 1 case with two lesions demonstrated a slight hyperattenuating margin, respectively. Multiple scattered punctate calcifications were involved in 2 cases. 5 cases manifested hypointensity on in-phase imaging, 1 iso-intensity, and 4 iso-hypointensity on out-of-phase imaging. Progressive and centripetal enhancement were exhibited in 10 cases, spoke-wheel pattern in 3 cases, and nodular enhancement in 4 cases, respectively. The central fibrous scar was identified in 8 cases during delayed enhancement. Conclusion: Characteristics of SANTs on CT/MRI reflected the underlying pathology. Hypointensity on DWI and T2WI, and change of signal on T1 chemicalshift imaging were found to be due to hemosiderin deposition and fibrous tissue. Typical feature was a solitary, round, lobulated mass with a fibrous scar. Progressive and centripetal enhancement, spoke-wheel pattern, nodular enhancement, and delayed enhancement of central fibrous scar were observed.

CD38 as a pan-hematologic target for chimeric antigen receptor T cells.

Many hematologic malignancies are not curable with chemotherapy and require novel therapeutic approaches. Chimeric antigen receptor (CAR) T-cell therapy is 1 such approach that involves the transfer of T cells engineered to express CARs for a specific cell-surface antigen. CD38 is a validated tumor antigen in multiple myeloma (MM) and T-cell acute lymphoblastic leukemia (T-ALL) and is also overexpressed in acute myeloid leukemia (AML). Here, we developed human CD38-redirected T cells (CART-38) as a unified approach to treat 3 different hematologic malignancies that occur across the pediatric-to-adult age spectrum. Importantly, CD38 expression on activated T cells did not impair CART-38 cells expansion or in vitro function. In xenografted mice, CART-38 mediated the rejection of AML, T-ALL, and MM cell lines and primary samples and prolonged survival. In a xenograft model of normal human hematopoiesis, CART-38 resulted in the expected reduction of hematopoietic progenitors, which warrants caution and careful monitoring of this potential toxicity when translating this new immunotherapy into the clinic. Deploying CART-38 against multiple CD38-expressing malignancies is significant because it expands the potential for this novel therapy to affect diverse patient populations.

Prostate Ultrasound Image Segmentation Based on DSU-Net.

In recent years, the incidence of prostate cancer in the male population has been increasing year by year. Transrectal ultrasound (TRUS) is an important means of prostate cancer diagnosis. The accurate segmentation of the prostate in TRUS images can assist doctors in needle biopsy and surgery and is also the basis for the accurate identification of prostate cancer. Due to the asymmetric shape and blurred boundary line of the prostate in TRUS images, it is difficult to obtain accurate segmentation results with existing segmentation methods. Therefore, a prostate segmentation method called DSU-Net is proposed in this paper. This proposed method replaces the basic convolution in the U-Net model with the improved convolution combining shear transformation and deformable convolution, making the network more sensitive to border features and more suitable for prostate segmentation tasks. Experiments show that DSU-Net has higher accuracy than other existing traditional segmentation methods.

Generation of FeIV =O and its Contribution to Fenton-Like Reactions on a Single-Atom Iron-N-C Catalyst.

Generating FeIV =O on single-atom catalysts by Fenton-like reaction has been established for water treatment; however, the FeIV =O generation pathway and oxidation behavior remain obscure. Employing an Fe-N-C catalyst with a typical Fe-N4 moiety to activate peroxymonosulfate (PMS), we demonstrate that generating FeIV =O is mediated by an Fe-N-C-PMS* complex-a well-recognized nonradical species for induction of electron-transfer oxidation-and we determined that adjacent Fe sites with a specific Fe1 -Fe1 distance are required. After the Fe atoms with an Fe1 -Fe1 distance <4 Šare PMS-saturated, Fe-N-C-PMS* formed on Fe sites with an Fe1 -Fe1 distance of 4-5 Šcan coordinate with the adjacent FeII -N4 , forming an inter-complex with enhanced charge transfer to produce FeIV =O. FeIV =O enables the Fenton-like system to efficiently oxidize various pollutants in a substrate-specific, pH-tolerant, and sustainable manner, where its prominent contribution manifests for pollutants with higher one-electron oxidation potential.

Anti-BCMA/CD19 CAR T Cells with Early Immunomodulatory Maintenance for Multiple Myeloma Responding to Initial or Later-Line Therapy.

We conducted a phase I clinical trial of anti-BCMA chimeric antigen receptor T cells (CART-BCMA) with or without anti-CD19 CAR T cells (huCART19) in multiple myeloma (MM) patients responding to third- or later-line therapy (phase A, N = 10) or high-risk patients responding to first-line therapy (phase B, N = 20), followed by early lenalidomide or pomalidomide maintenance. We observed no high-grade cytokine release syndrome (CRS) and only one instance of low-grade neurologic toxicity. Among 15 subjects with measurable disease, 10 exhibited partial response (PR) or better; among 26 subjects responding to prior therapy, 9 improved their response category and 4 converted to minimal residual disease (MRD)-negative complete response/stringent complete response. Early maintenance therapy was safe, feasible, and coincided in some patients with CAR T-cell reexpansion and late-onset, durable clinical response. Outcomes with CART-BCMA + huCART19 were similar to CART-BCMA alone. Collectively, our results demonstrate favorable safety, pharmacokinetics, and antimyeloma activity of dual-target CAR T-cell therapy in early lines of MM treatment. SIGNIFICANCE: CAR T cells in early lines of MM therapy could be safer and more effective than in the advanced setting, where prior studies have focused. We evaluated the safety, pharmacokinetics, and efficacy of CAR T cells in patients with low disease burden, responding to current therapy, combined with standard maintenance therapy. This article is highlighted in the In This Issue feature, p. 101.

Clinical evaluation of deep learning-based clinical target volume three-channel auto-segmentation algorithm for adaptive radiotherapy in cervical cancer.

OBJECTIVES: Accurate contouring of the clinical target volume (CTV) is a key element of radiotherapy in cervical cancer. We validated a novel deep learning (DL)-based auto-segmentation algorithm for CTVs in cervical cancer called the three-channel adaptive auto-segmentation network (TCAS). METHODS: A total of 107 cases were collected and contoured by senior radiation oncologists (ROs). Each case consisted of the following: (1) contrast-enhanced CT scan for positioning, (2) the related CTV, (3) multiple plain CT scans during treatment and (4) the related CTV. After registration between (1) and (3) for the same patient, the aligned image and CTV were generated. Method 1 is rigid registration, method 2 is deformable registration, and the aligned CTV is seen as the result. Method 3 is rigid registration and TCAS, method 4 is deformable registration and TCAS, and the result is generated by a DL-based method. RESULTS: From the 107 cases, 15 pairs were selected as the test set. The dice similarity coefficient (DSC) of method 1 was 0.8155 ± 0.0368; the DSC of method 2 was 0.8277 ± 0.0315; the DSCs of method 3 and 4 were 0.8914 ± 0.0294 and 0.8921 ± 0.0231, respectively. The mean surface distance and Hausdorff distance of methods 3 and 4 were markedly better than those of method 1 and 2. CONCLUSIONS: The TCAS achieved comparable accuracy to the manual delineation performed by senior ROs and was significantly better than direct registration.

Fortilin interacts with TGF-ß1 and prevents TGF-ß receptor activation.

Fortilin is a 172-amino acid multifunctional protein present in both intra- and extracellular spaces. Although fortilin binds and regulates various cellular proteins, the biological role of extracellular fortilin remains unknown. Here we report that fortilin specifically interacts with TGF-ß1 and prevents it from activating the TGF-ß1 signaling pathway. In a standard immunoprecipitation-western blot assay, fortilin co-immunoprecipitates TGF-ß1 and its isoforms. The modified ELISA assay shows that TGF-ß1 remains complexed with fortilin in human serum. Both bio-layer interferometry and surface plasmon resonance (SPR) reveal that fortilin directly bind TGF-ß1. The SPR analysis also reveals that fortilin and the TGF-ß receptor II (TGFßRII) compete for TGF-ß1. Both luciferase and secreted alkaline phosphatase reporter assays show that fortilin prevents TGF-ß1 from activating Smad3 binding to Smad-binding element. Fortilin inhibits the phosphorylation of Smad3 in both quantitative western blot assays and ELISA. Finally, fortilin inhibits TGFß-1-induced differentiation of C3H10T1/2 mesenchymal progenitor cells to smooth muscle cells. A computer-assisted virtual docking reveals that fortilin occupies the pocket of TGF-ß1 that is normally occupied by TGFßRII and that TGF-ß1 can bind either fortilin or TGFßRII at any given time. These data support the role of extracellular fortilin as a negative regulator of the TGF-ß1 signaling pathway.

Deep learning-based auto-segmentation of clinical target volumes for radiotherapy treatment of cervical cancer.

OBJECTIVES: Because radiotherapy is indispensible for treating cervical cancer, it is critical to accurately and efficiently delineate the radiation targets. We evaluated a deep learning (DL)-based auto-segmentation algorithm for automatic contouring of clinical target volumes (CTVs) in cervical cancers. METHODS: Computed tomography (CT) datasets from 535 cervical cancers treated with definitive or postoperative radiotherapy were collected. A DL tool based on VB-Net was developed to delineate CTVs of the pelvic lymph drainage area (dCTV1) and parametrial area (dCTV2) in the definitive radiotherapy group. The training/validation/test number is 157/20/23. CTV of the pelvic lymph drainage area (pCTV1) was delineated in the postoperative radiotherapy group. The training/validation/test number is 272/30/33. Dice similarity coefficient (DSC), mean surface distance (MSD), and Hausdorff distance (HD) were used to evaluate the contouring accuracy. Contouring times were recorded for efficiency comparison. RESULTS: The mean DSC, MSD, and HD values for our DL-based tool were 0.88/1.32 mm/21.60 mm for dCTV1, 0.70/2.42 mm/22.44 mm for dCTV2, and 0.86/1.15 mm/20.78 mm for pCTV1. Only minor modifications were needed for 63.5% of auto-segmentations to meet the clinical requirements. The contouring accuracy of the DL-based tool was comparable to that of senior radiation oncologists and was superior to that of junior/intermediate radiation oncologists. Additionally, DL assistance improved the performance of junior radiation oncologists for dCTV2 and pCTV1 contouring (mean DSC increases: 0.20 for dCTV2, 0.03 for pCTV1; mean contouring time decrease: 9.8 min for dCTV2, 28.9 min for pCTV1). CONCLUSIONS: DL-based auto-segmentation improves CTV contouring accuracy, reduces contouring time, and improves clinical efficiency for treating cervical cancer.

DNA methylation biomarkers for diagnosis of primary liver cancer and distinguishing hepatocellular carcinoma from intrahepatic cholangiocarcinoma.

Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are the two most common pathology subtypes of primary liver cancer (PLC). Identifying DNA methylation biomarkers for diagnosis of PLC and further distinguishing HCC from ICC plays a vital role in subsequent treatment options selection. To obtain potential diagnostic DNA methylation sites for PLC, differentially methylated CpG (DMC) sites were first screened by comparing the methylation data between normal liver samples and PLC samples (ICC samples and HCC samples). A random forest algorithm was then used to select specific DMC sites with top Gini value. To avoid overfitting, another cohort was taken as an external validation for evaluating the area under curves (AUCs) of different DMC sites combination. A similar model construction strategy was applied to distinguish HCC from ICC. In addition, we identified DNA Methylation-Driven Genes in HCC and ICC via MethylMix method and performed pathway analysis by utilizing MetaCore. Finally, we not only performed methylator phenotype based on independent prognostic sites but also analyzed the correlations between methylator phenotype and clinical factors in HCC and ICC, respectively. To diagnose PLC, we developed a model based on three PLC-specific methylation sites (cg24035245, cg21072795, and cg00261162), whose sensitivity and specificity achieved 98.8%,94.8% in training set and 97.3%,81% in validation set. Then, to further divide the PLC samples into HCC and ICC, we established another mode through three methylation sites (cg17769836, cg17591574, and cg07823562), HCC accuracy and ICC accuracy achieved 95.8%, 89.8% in the training set and 96.8%,85.4% in the validation set. In HCC, the enrichment pathways were mainly related to protein folding, oxidative stress, and glutathione metabolism. While in ICC, immune response, embryonic hepatocyte maturation were the top pathways. Both in HCC and ICC, methylator phenotype correlated well with overall survival time and clinical factors involved in tumor progression. In summary, our study provides the biomarkers based on methylation sites not only for the diagnosis of PLC but also for distinguishing HCC from ICC.

Differentiating TP53 Mutation Status in Pancreatic Ductal Adenocarcinoma Using Multiparametric MRI-Derived Radiomics.

OBJECTIVES: This study assessed the preoperative prediction of TP53 status based on multiparametric magnetic resonance imaging (mpMRI) radiomics extracted from two-dimensional (2D) and 3D images. METHODS: 57 patients with pancreatic cancer who underwent preoperative MRI were included. The diagnosis and TP53 gene test were based on resections. Of the 57 patients included 37 mutated TP53 genes and the remaining 20 had wild-type TP53 genes. Two radiologists performed manual tumour segmentation on seven different MRI image acquisition sequences per patient, including multi-phase [pre-contrast, late arterial phase (ap), portal venous phase, and delayed phase] dynamic contrast enhanced (DCE) T1-weighted imaging, T2-weighted imaging (T2WI), Diffusion-weighted imaging (DWI), and apparent diffusion coefficient (ADC). PyRadiomics-package was used to generate 558 two-dimensional (2D) and 994 three-dimensional (3D) image features. Models were constructed by support vector machine (SVM) for differentiating TP53 status and DX score method were used for feature selection. The evaluation of the model performance included area under the curve (AUC), accuracy, calibration curves, and decision curve analysis. RESULTS: The 3D ADC-ap-DWI-T2WI model with 11 selected features yielded the best performance for differentiating TP53 status, with accuracy = 0.91 and AUC = 0.96. The model showed the good calibration. The decision curve analysis indicated that the radiomics model had clinical utility. CONCLUSIONS: A non-invasive and quantitative mpMRI-based radiomics model can accurately predict TP53 mutation status in pancreatic cancer patients and contribute to the precision treatment.

The diagnosis of a giant cardiac malignant lymphoma in the right ventricle: a case report.

Cardiac lymphoma is extremely rare in patients with normal immune function and difficult to identify through routine examinations in patients with atypical clinical manifestations, making early diagnosis very difficult. We reported a 71-year-old male patient who was repeatedly diagnosed of pulmonary infection, suspected lung tumour, and Kimura disease in other hospital due to cough, expectoration, and dyspnoea. Later on, the patient visited our hospital due to heart failure and epistaxis. Transthoracic echocardiogram confirmed the presence of a space-occupying lesion in the right heart, cardiac magnetic resonance imaging preliminarily determined the nature of this lesion, finally, 18 F-fluorodeoxyglucose positron-emission tomography/computed tomography, and nasal mass biopsy confirmed the diagnosis of cardiac malignant lymphoma, and the pathological type was diffuse large B-cell lymphoma.

Erratum: MicroRNA-183-5p promotes the proliferation, invasion and metastasis of human pancreatic adenocarcinoma cells.

[This corrects the article DOI: 10.3892/ol.2015.3872.].

Pancreatic Neuroendocrine Neoplasms: CT Spectral Imaging in Grading.

RATIONALE AND OBJECTIVES: The purpose of this study was to define the CT spectral imaging characteristics of pancreatic neuroendocrine neoplasms (PNENs) and evaluate their potential for differential diagnosis of nonlow grade (non-LG) PNENs from low grade (LG) PNENs. MATERIALS AND METHODS: CT spectral imaging data of 54 pathologically proven PNENs were retrospectively reviewed. Patients were divided into two groups: 40 cases with grade 1 in LG PNENs group and 14 cases with grade 2 and grade 3 in non-LG PNENs group. RESULTS: Gender, calcification, inhomogeneity, invasiveness, PD dilatation, lymph node enlargement, size, normalized iodine (water) concentration in arterial phase (AP) (Iodine (ap)), normalized effective-Z (Zap), slope of normalized CT spectral curves in both AP, and portal venous phase were found to be significant variables for differentiating non-LG PNENs from LG PNENs (p < 0.05). Non-LG PNENs had larger size and lower Zap and Iodine (ap) than LG PNENs. The tumor size, Zap and Iodine (ap) had fair to good diagnostic performance with the area under receiver-operating-characteristic curve (AUC) 0.843, 0.733, and 0.728, respectively. Multivariate analysis with logistic regression had higher AUC (p<0.05) than all the single parameters except for size. CONCLUSION: There were significant differences in CT spectral imaging parameters between non-LG and LG PNENs. Tumor size was the most promising independent parameter and the combination of quantitative parameters with qualitative parameters is the best predictor in differentiating of non-LG PNENs from LG PNENs. CT spectral imaging can help determine the malignancy of PNENs, which can better assist in surgical planning.

Comprehensive Analysis for Identifying Diagnostic and Prognostic Biomarkers in Colon Adenocarcinoma.

Colon adenocarcinoma (COAD) is a common noncutaneous carcinoma worldwide with high morbidity and mortality. Effective prevention methods are far from being met. Both diagnostic and prognostic models that can precisely and accurately predict the status and survival time of COAD are urgently needed. In the field of COAD, there have been limited studies on molecular biomarkers that can predict disease status and prognosis. Hence, an important task is to identify these biomarkers. We aimed to identify important risk genes that have the ability not only to diagnose tumors but also to predict overall survival. A comprehensive analysis was performed in this study. Finally, carbonic anhydrase 1 (CA1) and CA4 were identified as potential biomarkers due to their predictive roles in diagnosis and prognosis, and the results were further confirmed by a series of analyses. Overall, these findings are of great importance and may facilitate individualized treatment in diagnosis and prognosis.

Resectable pancreatic ductal adenocarcinoma: association between preoperative CT texture features and metastatic nodal involvement.

BACKGROUND: To explore the relationship between the lymph node status and preoperative computed tomography images texture features in pancreatic cancer. METHODS: A total of 155 operable pancreatic cancer patients (104 men, 51 women; mean age 63.8 ± 9.6 years), who had undergone contrast-enhanced computed tomography in the arterial and portal venous phases, were enrolled in this retrospective study. There were 73 patients with lymph node metastases and 82 patients without nodal involvement. Four different data sets, with thin (1.25 mm) and thick (5 mm) slices (at arterial phase and portal venous phase) were analysed. Texture analysis was performed by using MaZda software. A combination of feature selection algorithms was used to determine 30 texture features with the optimal discriminative performance for differentiation between lymph node positive and negative groups. The prediction performance of the selected feature was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: There were 10 texture features with significant differences between two groups and significance in ROC analysis were identified. They were WavEnLH_s-2(wavelet energy with rows and columns are filtered with low pass and high pass frequency bands with scale factors 2) from wavelet-based features, 135dr_LngREmph (long run emphasis in 135 direction) and 135dr_Fraction (fraction of image in runs in 135 direction) from run length matrix-based features, and seven variables of sum average from coocurrence matrix-based features (SumAverg). The ideal cutoff value for predicting lymph node metastases was 270 for WavEnLH_s-2 (positive likelihood ratio 2.08). In addition, 135dr_LngREmph and 135dr_Fraction were correlated with the ratio of metastatic to examined lymph nodes. CONCLUSIONS: Preoperative computed tomography high order texture features provide a useful imaging signature for the prediction of nodal involvement in pancreatic cancer.

Clinicopathologic characterization and abnormal autophagy of CSF1R-related leukoencephalopathy.

BACKGROUND: CSF1R-related leukoencephalopathy, also known as hereditary diffuse leukoencephalopathy with spheroids (HDLS), is a rare white-matter encephalopathy characterized by motor and neuropsychiatric symptoms due to colony-stimulating factor 1 receptor (CSF1R) gene mutation. Few of CSF1R mutations have been functionally testified and the pathogenesis remains unknown. METHODS: In order to investigate clinical and pathological characteristics of patients with CSF1R-related leukoencephalopathy and explore the potential impact of CSF1R mutations, we analyzed clinical manifestations of 15 patients from 10 unrelated families and performed brain biopsy in 2 cases. Next generation sequencing was conducted for 10 probands to confirm the diagnosis. Sanger sequencing, segregation analysis and phenotypic reevaluation were utilized to substantiate findings. Functional examination of identified mutations was further explored. RESULTS: Clinical and neuroimaging characteristics were summarized. The average age at onset was 35.9 ± 6.4 years (range 24-46 years old). Younger age of onset was observed in female than male (34.2 vs. 39.2 years). The most common initial symptoms were speech dysfunction, cognitive decline and parkinsonian symptoms. One patient also had marked peripheral neuropathy. Brain biopsy of two cases showed typical pathological changes, including myelin loss, axonal spheroids, phosphorylated neurofilament and activated macrophages. Electron microscopy disclosed increased mitochondrial vacuolation and disorganized neurofilaments in ballooned axons. A total of 7 pathogenic variants (4 novel, 3 documented) were identified with autophosphorylation deficiency, among which c.2342C > T remained partial function of autophosphorylation. Western blotting disclosed the significantly lower level of c.2026C > T (p.R676*) than wild type. The level of microtubule associated protein 1 light chain 3-II (LC3-II), a classical marker of autophagy, was significantly lower in mutants expressed cells than wild type group by western blotting and immunofluorescence staining. CONCLUSIONS: Our findings support the loss-of-function and haploinsufficiency hypothesis in pathogenesis. Autophagy abnormality may play a role in the disease. Repairing or promoting the phosphorylation level of mutant CSF1R may shed light on therapeutic targets in the future. However, whether peripheral polyneuropathy potentially belongs to CSF1R-related spectrum deserves further study with longer follow-up and more patients enrolled. TRIAL REGISTRATION: ChiCTR, ChiCTR1800015295. Registered 21 March 2018.

The diagnostic and prognostic role of RhoA in hepatocellular carcinoma.

The aim of this study was to investigate the expression level of Ras homolog gene family, member A (RhoA) in patients with hepatocellular carcinoma (HCC) and to investigate the prognostic and diagnostic value of RhoA. Data mining from various data bases and wet experiments on samples from Peking Union Medical College Hospital showed that RhoA mRNA and protein expression were significantly higher in the HCC tissues than in the normal tissues. Higher expression at both the mRNA and protein levels was associated with a poorer prognosis. High sensitivity (92.5%) and specificity (90.0%) were observed in the diagnostic model based on protein level rather than mRNA level. RhoA expression was modulated by genetic amplification. The lysosome, pathogenic Escherichia coli infection, purine metabolism and pyrimidine metabolism pathways were mainly enriched in the high RhoA level group, while the hedgehog signaling, linoleic acid metabolism, olfactory transduction and taste transduction pathways were enriched in the low RhoA level group. RhoA is commonly upregulated in HCC tissues, and its expression at both the mRNA and protein levels is associated with poor prognosis. Notably, RhoA protein levels serve as a diagnostic biomarker for HCC.