Advancing targeted combination chemotherapy in triple negative breast cancer: nucleolin aptamer-mediated controlled drug release.

BACKGROUND: Triple-negative breast cancer (TNBC) is a recurrent, heterogeneous, and invasive form of breast cancer. The treatment of TNBC patients with paclitaxel and fluorouracil in a sequential manner has shown promising outcomes. However, it is challenging to deliver these chemotherapeutic agents sequentially to TNBC tumors. We aim to explore a precision therapy strategy for TNBC through the sequential delivery of paclitaxel and fluorouracil. METHODS: We developed a dual chemo-loaded aptamer with redox-sensitive caged paclitaxel for rapid release and non-cleavable caged fluorouracil for slow release. The binding affinity to the target protein was validated using Enzyme-linked oligonucleotide assays and Surface plasmon resonance assays. The targeting and internalization abilities into tumors were confirmed using Flow cytometry assays and Confocal microscopy assays. The inhibitory effects on TNBC progression were evaluated by pharmacological studies in vitro and in vivo. RESULTS: Various redox-responsive aptamer-paclitaxel conjugates were synthesized. Among them, AS1411-paclitaxel conjugate with a thioether linker (ASP) exhibited high anti-proliferation ability against TNBC cells, and its targeting ability was further improved through fluorouracil modification. The fluorouracil modified AS1411-paclitaxel conjugate with a thioether linker (FASP) exhibited effective targeting of TNBC cells and significantly improved the inhibitory effects on TNBC progression in vitro and in vivo. CONCLUSIONS: This study successfully developed fluorouracil-modified AS1411-paclitaxel conjugates with a thioether linker for targeted combination chemotherapy in TNBC. These conjugates demonstrated efficient recognition of TNBC cells, enabling targeted delivery and controlled release of paclitaxel and fluorouracil. This approach resulted in synergistic antitumor effects and reduced toxicity in vivo. However, challenges related to stability, immunogenicity, and scalability need to be further investigated for future translational applications.

Dual Control of Enhanced Quasi-Bound States in the Continuum Emission from Resonant c-Si Metasurfaces.

Optical bound states in the continuum (BICs) offer strong interactions with quantum emitters and have been extensively studied for manipulating spontaneous emission, lasing, and polariton Bose-Einstein condensation. However, the out-coupling efficiency of quasi-BIC emission, crucial for practical light-emitting devices, has received less attention. Here, we report an adaptable approach for enhancing quasi-BIC emission from a resonant monocrystalline silicon (c-Si) metasurface through lattice and multipolar engineering. We identify dual-BICs originating from electric quadrupoles (EQ) and out-of-plane magnetic dipoles, with EQ quasi-BICs exhibiting concentrated near-fields near the c-Si nanodisks. The enhanced fractional radiative local density of states of EQ quasi-BICs overlaps spatially with the emitters, promoting efficient out-coupling. Furthermore, coupling the EQ quasi-BICs with Rayleigh anomalies enhances directional emission intensity, and we observe inherent opposite topological charges in the multipolarly controlled dual-BICs. These findings provide valuable insights for developing efficient nanophotonic devices based on quasi-BICs.

Inhibiting Osteolytic Breast Cancer Bone Metastasis by Bone-Targeted Nanoagent via Remodeling the Bone Tumor Microenvironment Combined with NIR-II Photothermal Therapy.

Bone is one of the prone metastatic sites of patients with advanced breast cancer. The "vicious cycle" between osteoclasts and breast cancer cells plays an essential role in osteolytic bone metastasis from breast cancer. In order to inhibit bone metastasis from breast cancer, NIR-II photoresponsive bone-targeting nanosystems (CuP@PPy-ZOL NPs) are designed and synthesized. CuP@PPy-ZOL NPs can trigger the photothermal-enhanced Fenton response and photodynamic effect to enhance the photothermal treatment (PTT) effect and thus achieve synergistic anti-tumor effect. Meanwhile, they exhibit a photothermal enhanced ability to inhibit osteoclast differentiation and promote osteoblast differentiation, which reshaped the bone microenvironment. CuP@PPy-ZOL NPs effectively inhibited the proliferation of tumor cells and bone resorption in the in vitro 3D bone metastases model of breast cancer. In a mouse model of breast cancer bone metastasis, CuP@PPy-ZOL NPs combined with PTT with NIR-II significantly inhibited the tumor growth of breast cancer bone metastases and osteolysis while promoting bone repair to achieve the reversal of osteolytic breast cancer bone metastases. Furthermore, the potential biological mechanisms of synergistic treatment are identified by conditioned culture experiments and mRNA transcriptome analysis. The design of this nanosystem provides a promising strategy for treating osteolytic bone metastases.

Precisely constructing hybrid nanogap arrays via wet-transfer of dielectric metasurfaces onto a plasmonic mirror.

We propose a new method for fabricating hybrid metasurfaces by combining Mie and plasmonic resonances. Our approach involves obtaining an ultrasmooth gold film and separately structuring monocrystalline silicon (c-Si) nanoantenna arrays, which are then wet-transferred and finally immobilized onto the gold film. The experimental and simulation analysis reveals the importance of the native oxide layer of Si and demonstrates fascinating dispersion curves with nanogap resonances and bound states in the continuum. The localized field enhancements in the nanogap cavities result from the coupling between multipolar Mie resonances and their mirror images in the gold film. This effective method improves our understanding of hybrid modes and offers opportunities for developing active metasurfaces, such as depositing c-Si nanoantenna arrays onto stretchable polydimethylsiloxane substrates or electro-optic and piezoelectric sensitive lithium niobate films for potential applications in MEMS, LiDAR, and beyond.

Climate-driven vegetation greening further reduces water availability in drylands.

Climate change alters surface water availability (WA; precipitation minus evapotranspiration, P - ET) and consequently impacts agricultural production and societal water needs, leading to increasing concerns on the sustainability of water use. Although the direct effects of climate change on WA have long been recognized and assessed, indirect climate effects occurring through adjustments in terrestrial vegetation are more subtle and not yet fully quantified. To address this knowledge gap, here we investigate the interplay between climate-induced changes in leaf area index (LAI) and ET and quantify its ultimate effect on WA during the period 1982-2016 at the global scale, using an ensemble of data-driven products and land surface models. We show that ~44% of the global vegetated land has experienced a significant increase in growing season-averaged LAI and climate change explains 33.5% of this greening signal. Such climate-induced greening has enhanced ET of 0.051 ± 0.067 mm year-2 (mean ± SD), further amplifying the ongoing increase in ET directly driven by variations in climatic factors over 36.8% of the globe, and thus exacerbating the decline in WA prominently in drylands. These findings highlight the indirect impact of positive feedbacks in the land-climate system on the decline of WA, and call for an in-depth evaluation of these phenomena in the design of local mitigation and adaptation plans.

Apolipoprotein B is associated with CT-angiographic progression beyond low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol in patients with coronary artery disease.

BACKGROUND: Accumulating evidence indicated that apolipoprotein B (apoB) was the principal lipid determinant of coronary artery disease (CAD). Nevertheless, the connection between apoB and angiographic progression of CAD remained undetermined. METHODS: Five hundred and forty-four CAD patients with twice coronary computed tomography angiography experiences were enrolled. The Gensini scoring system was used to assess angiographic progression. Incident angiographic progression was defined as an annual change rate of the Gensini score of > 1 point. The predictive efficacy of baseline apoB levels for angiographic progression was assessed using a receiver operating characteristic (ROC) curve. For comparative purposes, patients were categorized into three groups according to their baseline apoB tertiles. Furthermore, discordance analyses defined by the median were performed to assess the superiority of apoB over lipoprotein cholesterol in predicting angiographic progression of CAD. RESULTS: Angiographic progression was observed in 184 patients (33.8%) during a follow-up period of 2.2-year. The area under the ROC curve was 0.565 (0.522-0.607, P = 0.013). The incidence of angiographic progression was elevated with increasing apoB tertile after adjusting for confounding factors [odds ratio (OR) for the medium apoB tertile: 1.92, 95% confidence interval (CI): 1.15-3.19, P = 0.012; OR for the high apoB tertile: 2.05, 95%CI:1.17-3.60, P = 0.013]. Additionally, discordance analyses showed that the higher apoB group had a significantly higher risk of CAD progression in the fully adjusted model (all P < 0.05). CONCLUSIONS: ApoB could be used as an accurate and comprehensive indicator of angiographic progression in patients with CAD.

Novel recombinant R-spondin1 promotes hair regeneration by targeting the Wnt/ß-catenin signaling pathway.

Roof plate-specific spondin 1 (R-spondin1, RSPO1) is a Wnt/ß-catenin signaling pathway activator that binds with Wnt ligands to stimulate the Wnt/ß-catenin signaling pathway, which is key to hair regeneration. However, it is not clear whether recombinant RSPO1 (rRSPO1) affects hair regeneration. Here, we treat C57BL/6 male mice with rRSPO1 and investigate the expression of the Wnt/ß-catenin signaling pathway and the activation of hair follicle stem cells in the dorsal skin. The mouse skin color score and hair-covered area are determined to describe hair growth, and the skin samples are subjected to H&E staining, western blot analysis and immunofluorescence staining to evaluate hair follicle development and the expressions of Wnt/ß-catenin signaling pathway-related proteins. We find that rRSPO1 activates mouse hair follicle stem cells (mHFSCs) and accelerates hair regeneration. rRSPO1 increases the hair-covered area, the number of hair follicles, and the hair follicle diameter and length. Moreover, rRSPO1 enhances the activity of Wnt/ß-catenin signaling pathway-related proteins and the expressions of HFSC markers, as well as mHFSC viability. These results indicate that subcutaneous injection of rRSPO1 can improve hair follicle development by activating the Wnt/ß-catenin signaling pathway, thereby promoting hair regeneration. This study demonstrates that rRSPO1 has the potential to treat hair loss by activating the Wnt/ß-catenin signaling pathway.

ATAD2 drives colorectal cancer progression by regulating TRIM25 expression via a positive feedback loop with E2F transcriptional factors.

ATPase family AAA domain-containing protein 2 (ATAD2) is highly expressed in a variety of cancer types, and acts as a co-activator of androgen and estrogen receptors, as well as MYC and E2F transcription factors, to promote tumor cell proliferation. However, the regulation of ATAD2 and its related mechanisms are still elusive. Here, we show that ATAD2 protein was stabilized during DNA damage response in colorectal cancer (CRC) cells. TRIM25, an oncogenic ubiquitin E3 ligase, can interact with ATAD2 and stabilize ATAD2 upon genotoxic insult. We further demonstrated that ATAD2 played a tumor promoting role in CRC and acted as a transcriptional co-activator of E2Fs to promote the expression of TRIM25. Thus, our results revealed an unknown ATAD2-E2Fs-TRIM25 positive feedback loop that drove CRC progression.

The USP18-FBXO6 axis maintains the malignancy of ovarian cancer.

Ubiquitin-specific protease 18 (USP18) is a deubiquitinating enzyme that reverses the post-translational modification of target proteins by ISG15 or ubiquitin, and is involved in a variety of cellular processes, including signal transduction, viral infection, and cancer development. Although high levels of USP18 mRNA have been observed in several types of cancer, its pathological significance in ovarian cancer (OV) is still elusive. Here, by integrating the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Genotypic Tissue Expression (GTEx) databases, we found that USP18 was abnormally up-regulated in OV tissues, and the increased expression of USP18 was associated with poor prognosis. We further showed that activated Jak-STAT3 signaling induced the expression of USP18, which in turn feedback maintained the activity of Jak-STAT3 signaling in OV. In addition, we found that USP18 played a cancer-promoting role in OV mainly through the transcriptional regulation of FBXO6. Silencing USP18 reduced the malignancy of OV, which can be largely reversed by overexpression of FBXO6. On the contrary, silencing FBXO6 significantly weaken the pro-proliferation function of USP18 in OV cells. In summary, our results indicate that USP18 is a downstream target gene of STAT3, and the USP18-FBXO6 axis might be a promising therapeutic target for OV.

SOX9-mediated UGT8 expression promotes glycolysis and maintains the malignancy of non-small cell lung cancer.

UDP-glycosyltransferases (UGTs) catalyze the covalent addition of sugars to small lipophilic chemicals and are associated with a wide range of diseases including cancer. The human genome contains 22 UGT genes which could be classified into four families: UGT1, UGT2, UGT3, and UGT8. The UGT8 family contains only one member which utilizes UDP galactose to galactosidate ceramide. Although higher UGT8 mRNA was observed in some types of cancer, its pathological significances remain elusive. Here, by integrating the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and the Genotype-Tissue Expression (GTEx) databases, we showed that UGT8 was selectively highly expressed in non-small cell lung cancer (NSCLC) and associated with worse prognosis. The transcription factor SOX9 promoted UGT8 expression in NSCLC by recognizing two putative response elements localized on the promoter region of UGT8. Silencing UGT8 impaired glycolysis and reduced the malignancy of NSCLC cells both in vitro and in vivo. On the contrary, inhibition of glycolysis by 2-deoxy-d-glucose (2-DG) significantly impaired the pro-proliferation function of UGT8 in NSCLC cells. In conclusion, our results suggest that UGT8 maintains the malignancy of NSCLC mainly via enhanced glycolysis and provides a promising therapeutic target for NSCLC.

Hybrid fiber-THz fronthaul supporting up to 16384-QAM-OFDM with the delta-sigma modulation.

With the progress of high-capacity radio access networks, ultra-dense small cells are rapidly being deployed in urban areas. As a result, the deployment of a large number of optical fibers in urban areas becomes a severe issue. In this Letter, we propose a hybrid fiber-terahertz (THz) mobile fronthaul system supporting flexible and high-order wireless signal transmission with the delta-sigma modulation. The photonic THz transmission is used as the seamless extension of fiber-based fronthaul in small cells. A 20-Gbit/s digital fiber-THz fronthaul system is experimentally demonstrated to validate the proposed scheme, with 10-km optical fiber transmission and 300-GHz wireless relay. Carrier aggregation of up to 10 40-MHz and 60-MHz 5G-new radio (5G-NR) channels at the radio carrier frequency of 3.9 GHz is reported. The design of quantization noise suppressed delta-sigma modulation enables the system to transmit orthogonal frequency division multiplexing (OFDM) modulation up to  16384 order quadrate amplitude modulation (QAM) mapping with the error vector magnitude (EVM) below 0.5%.

Association of serum sclerostin and osteoprotegerin levels with the presence, severity and prognosis in patients with acute myocardial infarction.

BACKGROUND: Bone-related proteins (such as sclerostin and osteoprotegerin [OPG]) are involved in the development of atherosclerosis. However, the relationship between bone-related proteins and acute myocardial infarction (AMI) has not been extensively evaluated. The purpose of this study was to assess the association of serum sclerostin and OPG with the presence, severity and prognosis in patients with AMI. METHODS: This study prospectively enrolled 152 patients attacked by acute chest pain. Serum sclerostin and OPG were detected within the first 24 h after AMI diagnosis by ELISA kits. The AMI predictive efficacy of sclerostin and OPG were analyzed by receiver operating characteristics (ROC) curve. Univariable and multivariable linear regression analyses were performed to determine the association between bone-related proteins and scores indicating the severity of coronary artery occlusion. Moreover, prognostic values were assessed by Kaplan-Meier curves and Cox regression analysis. RESULTS: There were 92 patients in AMI group, 60 in non-AMI group. Serum levels of sclerostin and OPG were significantly higher in AMI group than in non-AMI group (all p < 0.001), which showed predictive value for the presence of AMI (all p < 0.001). The area under the ROC curve values of sclerostin and OPG were 0.744 and 0.897, respectively. A multivariable linear regression analysis demonstrated that Ln-transformed sclerostin (ß = 0.288, p = 0.009) and Ln-transformed OPG (Ln-OPG: ß = 0.295, p = 0.019) levels were associated with GENISINI score, independently of conventional clinical parameters. In addition, Ln-OPG levels were still positively associated with GRACE score after adjustments (ß = 0.320, p = 0.001). During a 1-year follow-up, patients above the median of sclerostin levels had higher incidence of major adverse cardiac events (MACE) than those below the median (p = 0.028). It was also observed that the MACE rates were higher in patients above the median of OPG levels, though no statistic importance (p = 0.060). After adjusting conventional risk factors by multivariate Cox regression, Ln-OPG was associated with incident MACE (hazard ratio = 2.188 [95% confidence intervals 1.102-4.344], p = 0.025). CONCLUSIONS: Bone-related proteins could exert a potential role in early risk stratification and prognosis assessment in patients with AMI.

Design and Embedded Implementation of Secure Image Encryption Scheme Using DWT and 2D-LASM.

In order to further improve the information effectiveness of digital image transmission, an image-encryption algorithm based on 2D-Logistic-adjusted-Sine map (2D-LASM) and Discrete Wavelet Transform (DWT) is proposed. First, a dynamic key with plaintext correlation is generated using Message-Digest Algorithm 5 (MD5), and 2D-LASM chaos is generated based on the key to obtain a chaotic pseudo-random sequence. Secondly, we perform DWT on the plaintext image to map the image from the time domain to the frequency domain and decompose the low-frequency (LF) coefficient and high-frequency (HF) coefficient. Then, the chaotic sequence is used to encrypt the LF coefficient with the structure of "confusion-permutation". We perform the permutation operation on HF coefficient, and we reconstruct the image of the processed LF coefficient and HF coefficient to obtain the frequency-domain ciphertext image. Finally, the ciphertext is dynamically diffused using the chaotic sequence to obtain the final ciphertext. Theoretical analysis and simulation experiments show that the algorithm has a large key space and can effectively resist various attacks. Compared with the spatial-domain algorithms, this algorithm has great advantages in terms of computational complexity, security performance, and encryption efficiency. At the same time, it provides better concealment of the encrypted image while ensuring the encryption efficiency compared to existing frequency-domain methods. The successful implementation on the embedded device in the optical network environment verifies the experimental feasibility of this algorithm in the new network application.

Defect Etching of Phase-Transition-Assisted CVD-Grown 2H-MoTe2.

2D molybdenum ditelluride (MoTe2 ) with polymorphism is a promising candidate to developing phase-change memory, high-performance transistors and spintronic devices. The phase-transition-assisted chemical vapor deposition (CVD) process has been used to prepare large-scale 2H-MoTe2 with large grain size and low density of grain boundary. However, because of the lack of precise control of the growth condition, some defects including the amorphous regions and grain boundaries in 2H-MoTe2 are hardly avoidable. Here, a facile method of selectively etching defects in large-scale CVD-grown 2H-MoTe2 by triiodide ion (I3 - ) solution is reported. The defect etching is attributed to the reduced lattice symmetry, high chemisorption activity and high conductivity of the defects due to the high density of Te vacancies. The treated 2H-MoTe2 shows the suppressed hysteresis in the electrical transfer curve, enhances hole mobility and the higher effective barrier height on the metal contact, suggesting the decreased density of defects. Further chemical analysis indicates that the 2H-MoTe2 is not damaged or doped by I3 - solution during the etching process. This simple and low-cost post-processing method is effective for etching the defects in large-area 2H-MoTe2 for high-performance device applications.

Self-powered and high-performance all-fiber integrated photodetector based on graphene/palladium diselenide heterostructures.

An all-fiber integrated photodetector is proposed and demonstrated by assembling a graphene/palladium diselenide (PdSe2) Van der Waals heterostructure onto the endface of a standard optical fiber. A gold film is covered on the heterostructure working as an electrode and a mirror, which reflects back the unabsorbed residual light for further reusage. Owing to the low bandgap of PdSe2, the all-fiber photodetector shows a broadband photoresponse from 650 to 1550 nm with a high photoresponsivity of 6.68×104 AW-1, enabling a low light detection of 42.5 pW. And the fastest temporal response is about 660 µs. Taking advantage of heterostructures, the photodetector can work in self-powered mode with the on/off ratio about 82. These findings provide new strategies for integrating two-dimensional materials into optical fibers to realize integrated all-fiber devices with multi-function applications.

A mitochondria-targeted thiazoleorange-based photothermal agent for enhanced photothermal therapy for tumors.

Organic small molecules with near-infrared (NIR) absorption hold great promise as the phototheranostic agents for clinical translation by virtue of their inherent merits such as well-defined chemical structure, high purity and good reproducibility. Probes that happen to be based on cyanine dyes exhibit strong NIR-absorbing and efficient photothermal conversion, representing a new class of photothermal agents (PAs) for photothermal therapy (PTT), and taking into account the heat susceptibility of Mitochondria (Mito), we designed and prepared a mitochondria-targeted organic small molecule (Mito-BWQ) based on thiazole orange maternal unit that can effectively kill tumor cells through the hyperpyrexia generated in the lesions under exogenous laser irradiation. The Confocal laser scanning microscope was employed to determine the preferential targeting of Mito-BWQ to the mitochondria of MCF-7 cells and U87 cells. When subjected to 600 nm laser radiation, Mito-BWQ produced an increase in temperature in test systems and this increase was dependent on both the laser power and probe concentration. In vitro tests, cytotoxicity was observed when cells were incubated with Mito-BWQ and exposed to laser irradiation. The PTT in vivo also showed that Mito-BWQ performed remarkably in tumor inhibition. This study thus provides a vital starting point for the creation of thiazole orange-based PTT formulations and promotes further advances in the field of PAs-based anticancer research and therapy.

Photonic spin Hall effect in twisted bilayer graphene.

Here, we investigate the photonic spin Hall effect in twisted bilayer graphene. The optical conductivities for several rotation angles of twisted bilayer graphene are calculated by first principles, based on which a theoretical framework is established to describe the light-matter interaction. To enhance the photonic spin Hall effect, twisted bilayer graphene is placed on a BK7 glass substrate and a Gaussian beam is launched near the Brewster angle. The spin splitting as well as Goos-Hänchen shifts are investigated, which are associated, respectively, with the imaginary and real parts of the surface conductivities of the twisted bilayer graphene. These findings provide a deeper understanding of the photonic spin Hall effect in two-dimensional materials and have potential application in characterizing bilayer graphene.

Adiponectin affects estimated glomerular filtration rate: A two-sample bidirectional Mendelian randomization study.

BACKGROUND: The causal relationship between adiponectin (ADPN) and estimated glomerular filtration rate (eGFR) is unclear. This study adopts a two-sample bidirectional Mendelian randomization (MR) study to explore the causal relationship between ADPN and eGFR. METHODS: Using eight single nucleotide polymorphisms (SNP) of ADPN and 26 SNP of eGFR as instrumental variables, the study performs a two-sample bidirectional MR study using MR inverse-variance weighted (IVW), MR-Egger and weighted median approach to evaluate the causal relationship between ADPN and eGFR. Using the genetic risk score (GRS) of ADPN and eGFR as instrumental variables, the study performs a second MR analysis to assess the association between ADPN and eGFR. RESULTS: In ADPN to eGFR MR analysis, the IVW, weighted median and GRS analysis all showed that ADPN had a causal effect on eGFR after removing potential confounders of the ADPN-eGFR relation (IVW: ß = .016, P = .002; weighted median: ß = .012, P = .022; GRS: ß = .016, P = 1.48E-05). As both ADPN and eGFR were natural log-transformed in the corresponding GWAS, eGFR increased by 0.15% for any 10% increase in ADPN. In eGFR to ADPN MR analysis, eGFR had no causal effect on ADPN after removing potential confounders of the eGFR-ADPN relation (All P values > 0.05). The heterogeneity test and sensitivity analysis indicated some heterogeneity, but no directional pleiotropy. CONCLUSION: Adiponectin has a causal effect on eGFR, while eGFR has no causal effect on ADPN. ADPN may be a clinical target for improving eGFR and treating chronic kidney disease caused by decreased eGFR.

Graphene-assisted electro-optomechanical integration on a silicon-on-insulator platform.

Micro- and nano-optomechanics has attracted broad interest for applications of mechanical sensing and coherent signal processing. For nonpiezoelectric materials such as silicon or silicon nitride, electrocapacitive effects with metals patterned on mechanical structures are usually adopted to actuate the mechanical motion of the micro- or nanomechanical devices. However, the metals have deleterious effects on the mechanical structures because they add an additional weight and also introduce considerable mechanical losses. To solve these problems, we have proposed and experimentally demonstrated a new scheme of electro-optomechanical integration on a silicon-on-insulator platform by using single-layer graphene as a highly conductive coating for electromechanical actuation. Mechanical modes of different groups were electrically actuated and optically detected in a micromechanical resonator, with the mechanical Q > 1000 measured in air. Compatible with CMOS technology, our scheme is suitable for large-scale electro-optomechanical integration and will have wide applications in high-speed sensing, communication, and signal processing.

Development and validation of an RNA binding protein-associated prognostic model for hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is among the deadliest forms of cancer. While RNA-binding proteins (RBPs) have been shown to be key regulators of oncogenesis and tumor progression, their dysregulation in the context of HCC remains to be fully characterized. METHODS: Data from the Cancer Genome Atlas - liver HCC (TCGA-LIHC) database were downloaded and analyzed in order to identify RBPs that were differentially expressed in HCC tumors relative to healthy normal tissues. Functional enrichment analyses of these RBPs were then conducted using the GO and KEGG databases to understand their mechanistic roles. Central hub RBPs associated with HCC patient prognosis were then detected through Cox regression analyses, and were incorporated into a prognostic model. The prognostic value of this model was then assessed through the use of Kaplan-Meier curves, time-related ROC analyses, univariate and multivariate Cox regression analyses, and nomograms. Lastly, the relationship between individual hub RBPs and HCC patient overall survival (OS) was evaluated using Kaplan-Meier curves. Finally, find protein-coding genes (PCGs) related to hub RBPs were used to construct a hub RBP-PCG co-expression network. RESULTS: In total, we identified 81 RBPs that were differentially expressed in HCC tumors relative to healthy tissues (54 upregulated, 27 downregulated). Seven prognostically-relevant hub RBPs (SMG5, BOP1, LIN28B, RNF17, ANG, LARP1B, and NR0B1) were then used to generate a prognostic model, after which HCC patients were separated into high- and low-risk groups based upon resultant risk score values. In both the training and test datasets, we found that high-risk HCC patients exhibited decreased OS relative to low-risk patients, with time-dependent area under the ROC curve values of 0.801 and 0.676, respectively. This model thus exhibited good prognostic performance. We additionally generated a prognostic nomogram based upon these seven hub RBPs and found that four other genes were significantly correlated with OS. CONCLUSION: We herein identified a seven RBP signature that can reliably be used to predict HCC patient OS, underscoring the prognostic relevance of these genes.