Methylated circulating tumor DNA in hepatocellular carcinoma: A comprehensive analysis of biomarker potential and clinical implications.

The intricate epigenetic landscape of hepatocellular carcinoma (HCC) is profoundly influenced by alterations in DNA methylation patterns. Understanding these alterations is crucial for unraveling the molecular mechanisms underlying HCC pathogenesis. Methylated circulating tumor DNA (ctDNA) presents itself as an encouraging avenue for biomarker discovery and holds substantial clinical implications in HCC management. This review comprehensively outlines the studies concerning DNA methylation in HCC and underscores the significance of methylated ctDNA within this context. Moreover, a variety of cfDNA methylation-based methodologies, such as 5hmC profiling, bisulfite-based, restriction enzyme-dependent, and enrichment-based methods, provide in-depth insights into the molecular pathology of HCC. Additionally, the integration of methylated ctDNA analysis into clinical practice represents a significant advancement in personalized HCC management. By facilitating cancer screening, prognosis assessment, and treatment response prediction, the utilization of methylated ctDNA signifies a pivotal stride toward enhancing patient care and outcomes in HCC.

Purinosomes involved in the regulation of tumor metabolism: current progress and potential application targets.

The core of tumor cell metabolism is the management of energy metabolism due to the extremely high energy requirements of tumor cells. The purine nucleotide synthesis pathway in cells uses the purinosomes as an essential spatial structural complex. In addition to serving a crucial regulatory role in the emergence and growth of tumors, it contributes to the synthesis and metabolism of purine nucleotides. The significance of purine metabolism in tumor cells is initially addressed in this current article. The role of purinosomes as prospective therapeutic targets is then reviewed, along with a list of the signaling pathways that play in the regulation of tumor metabolism. A thorough comprehension of the function of purinosomes in the control of tumor metabolism can generate fresh suggestions for the creation of innovative cancer treatment methods.

Exploring FGFR signaling inhibition as a promising approach in breast cancer treatment.

As our grasp of cancer genomics deepens, we are steadily progressing towards the domain of precision medicine, where targeted therapy stands out as a revolutionary breakthrough in the landscape of cancer therapeutics. The fibroblast growth factor receptors (FGFR) pathway has been unveiled as a fundamental instigator in the pathophysiological mechanisms underlying breast carcinoma, paving the way for the exhilarating development of precision-targeted therapeutics. In the pursuit of exploring inhibitors that specifically target the FGFR signaling pathways, a multitude of kinase inhibitors targeting FGFR has been assiduously engineered to address the heterogeneous landscape of human malignancies. This review offers an exhaustive exploration of aberrations within the FGFR pathway and their functional implications in breast cancer. Additionally, we delve into cutting-edge therapeutic approaches for the treatment of breast cancer patients bearing FGFR alterations and the management of toxicity associated with FGFR inhibitors. Furthermore, our contemplation of the evolution of cutting-edge FGFR inhibitors foresees their potential to spearhead innovative therapeutic approaches in the ongoing combat against cancer.

Pioneering the Way: The Revolutionary Potential of Antibody-Drug Conjugates in NSCLC.

OPINION STATEMENT: Despite targeted therapy and immunotherapy being recognized as established frontline treatments for advanced non-small cell lung cancer (NSCLC), the unavoidable development of resistance and disease progression poses ongoing challenges. Antibody-drug conjugates (ADCs) offer a potent treatment option for NSCLC through the specific delivery of cytotoxic agents to tumor cells that display distinct antigens. This review delves into the latest evidence regarding promising ADC agents for NSCLC, focusing on their targets, effectiveness, and safety assessments. Additionally, our study provides insights into managing toxicities, identifying biomarkers, devising methods to counter resistance mechanisms, tackling prevailing challenges, and outlining prospects for the clinical implementation of these innovative ADCs and combination regimens in NSCLC.

PIK3CA mutation as an acquired resistance driver to EGFR-TKIs in non-small cell lung cancer: Clinical challenges and opportunities.

Epithelial growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have significantly enhanced the treatment outcomes in non-small cell lung cancer (NSCLC) patients harboring EGFR mutations. However, the occurrence of acquired resistance to EGFR-TKIs is an unavoidable outcome observed in these patients. Disruption of the PI3K/AKT/mTOR signaling pathway can contribute to the emergence of resistance to EGFR TKIs in lung cancer. The emergence of PIK3CA mutations following treatment with EGFR-TKIs can lead to resistance against EGFR-TKIs. This review provides an overview of the current perspectives regarding the involvement of PI3K/AKT/mTOR signaling in the development of lung cancer. Furthermore, we outline the state-of-the-art therapeutic strategies targeting the PI3K/AKT/mTOR signaling pathway in lung cancer. We highlight the role of PIK3CA mutation as an acquired resistance mechanism against EGFR-TKIs in EGFR-mutant NSCLC. Crucially, we explore therapeutic strategies targeting PIK3CA-mediated resistance to EGFR TKIs in lung cancer, aiming to optimize the effectiveness of treatment.

CD137L Inhibition Ameliorates Hippocampal Neuroinflammation and Behavioral Deficits in a Mouse Model of Sepsis-Associated Encephalopathy.

Anxiety manifestations and cognitive dysfunction are common sequelae in patients with sepsis-associated encephalopathy (SAE). Microglia-mediated inflammatory signaling is involved in anxiety, depression, and cognitive dysfunction during acute infection with bacterial lipopolysaccharide (LPS). However, the molecular mechanisms underlying microglia activation and behavioral and cognitive deficits in sepsis have not been in fully elucidated. Based on previous research, we speculated that the CD137 receptor/ligand system modulates microglia function during sepsis to mediate classical neurological SAE symptoms. A murine model of SAE was established by injecting male C57BL/6 mice with LPS, and cultured mouse BV2 microglia were used for in vitro assays. RT-qPCR, immunofluorescence staining, flow cytometry, and ELISA were used to assess microglial activation and the expression of CD137L and inflammation-related cytokines in the mouse hippocampus and in cultured BV2 cells. In addition, behavioral tests were conducted in assess cognitive performance and behavioral distress. Immunofluorescence and RT-qPCR analyses showed that hippocampal expression of CD137L was upregulated in activated microglia following LPS treatment. Pre-treatment with the CD137L neutralizing antibody TKS-1 significantly reduced CD137L levels, attenuated the expression of M1 polarization markers in microglia, and inhibited the production of TNF-α, IL-1ß, and IL-6 in both LPS-treated mice and BV2 cells. Conversely, stimulation of CD137L signaling by recombinant CD137-Fc fusion protein activated the synthesis and release of pro-inflammatory cytokines in cultures BV2 microglia. Importantly, open field, elevated plus maze, and Y-maze spontaneous alternation test results indicated that TKS-1 administration alleviated anxiety-like behavior and spatial memory decline in mice with LPS-induced SAE. These findings suggest that CD137L upregulation in activated microglia critically contributes to neuroinflammation, anxiety-like behavior, and cognitive dysfunction in the mouse model of LPS-induced sepsis. Therefore, therapeutic modulation of the CD137L/CD137 signaling pathway may represent an effective way to minimize brain damage and prevent cognitive and emotional deficits associated with SAE.

J147 ameliorates sepsis-induced depressive-like behaviors in mice by attenuating neuroinflammation through regulating the TLR4/NF-κB signaling pathway.

Neuroinflammation is associated with the pathophysiology of depression. The molecular mechanism of depressive-like behavior caused by sepsis-associated encephalopathy (SAE) is incompletely understood. J147 (an analog of curcumin) has been reported to improve memory and has neuroprotective activity, but its biological function in the depressive-like behavior observed in SAE is not known. We investigated the effects of J147 on lipopolysaccharide (LPS)-induced neuroinflammatory, depressive-like behaviors, and the toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signal pathway in the mouse hippocampus and microglia (BV2 cells). The forced-swimming test (FST) and tail-suspension test (TST) were undertaken for assessment of depressive-like behaviors. Expression of the proinflammatory genes interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α were measured using RT-qPCR and ELISA. Microglia activation was detected using immunofluorescence staining. The TLR4/NF-κB signaling pathway was studied using western blotting and immunofluorescence staining. J147 pretreatment markedly downregulated expression of IL-6, IL-1ß, and TNF-α, and the mean fluorescence intensity of ionized calcium-binding adapter protein-1 in microglia. J147 restrained LPS-induced nuclear translocation of nuclear factor-kappa B (NF-κB), inhibitor of nuclear factor kappa B (IκB) degradation, and TLR4 activation in microglia. J147 administration inhibited bodyweight loss, mortality, microglia activation, and depressive-like behaviors in LPS-treated mice. In conclusion, J147 ameliorated the sepsis-induced depressive-like behaviors induced by neuroinflammation through attenuating the TLR4/NF-κB signaling pathway in microglia.

Current evidence for J147 as a potential therapeutic agent in nervous system disease: a narrative review.

Curcumin has anti-inflammatory, antioxidant, and anticancer effects and is used to treat diseases such as dermatological diseases, infection, stress, depression, and anxiety. J147, an analogue of curcumin, is designed and synthesized with better stability and bioavailability. Accumulating evidence demonstrates the potential role of J147 in the prevention and treatment of Alzheimer's disease, diabetic neuropathy, ischemic stroke, depression, anxiety, and fatty liver disease. In this narrative review, we summarized the background and biochemical properties of J147 and discussed the role and mechanism of J147 in different diseases. Overall, the mechanical attributes of J147 connote it as a potential target for the prevention and treatment of neurological diseases.

Combining Radiotherapy with Immunotherapy in Cervical Cancer: Where Do We Stand and Where Are We Going?

OPINION STATEMENT: Combining immunotherapy and radiotherapy as a treatment strategy for cervical cancer has attracted increasing attention. The primary objective of this review is to provide an up-to-date summary of the knowledge regarding the combined use of radiotherapy and immunotherapy for treating cervical cancer. This review discusses the biological rationale combining immunotherapy with radiotherapy in a clinical setting and presents supporting evidence for the combination strategy based on both safety and effectiveness data. Additionally, we discuss the potential and challenges of combining radiotherapy and immunotherapy in clinical practice.

Engineering Extracellular Matrix-Bound Nanovesicles Secreted by Three-Dimensional Human Mesenchymal Stem Cells.

Extracellular matrix (ECM) in the human tissue contains vesicles, which are defined as matrix-bound nanovesicles (MBVs). MBVs serve as one of the functional components in ECM, recapitulating part of the regulatory roles and in vivo microenvironment. In this study, extracellular vesicles from culture supernatants (SuEVs) and MBVs are isolated from the conditioned medium or ECM, respectively, of 3D human mesenchymal stem cells. Nanoparticle tracking analysis shows that MBVs are smaller than SuEVs (100-150 nm). Transmission electron microscopy captures the typical cup shape morphology for both SuEVs and MBVs. Western blot reveals that MBVs have low detection of some SuEV markers such as syntenin-1. miRNA analysis of MBVs shows that 3D microenvironment enhances the expression of miRNAs such as miR-19a and miR-21. In vitro functional analysis shows that MBVs can facilitate human pluripotent stem cell-derived forebrain organoid recovery after starvation and promote high passage fibroblast proliferation. In macrophage polarization, 2D MBVs tend to suppress the pro-inflammatory cytokine IL-12ß, while 3D MBVs tend to enhance the anti-inflammatory cytokine IL-10. This study has the significance in advancing the understanding of the bio-interface of nanovesicles with human tissue and the design of cell-free therapy for treating neurological disorders such as ischemic stroke.

Phase separation in cancer at a glance.

Eukaryotic cells are segmented into multiple compartments or organelles within the cell that regulate distinct chemical and biological processes. Membrane-less organelles are membrane-less microscopic cellular compartments that contain protein and RNA molecules that perform a wide range of functions. Liquid-liquid phase separation (LLPS) can reveal how membrane-less organelles develop via dynamic biomolecule assembly. LLPS either segregates undesirable molecules from cells or aggregates desired ones in cells. Aberrant LLPS results in the production of abnormal biomolecular condensates (BMCs), which can cause cancer. Here, we explore the intricate mechanisms behind the formation of BMCs and its biophysical properties. Additionally, we discuss recent discoveries related to biological LLPS in tumorigenesis, including aberrant signaling and transduction, stress granule formation, evading growth arrest, and genomic instability. We also discuss the therapeutic implications of LLPS in cancer. Understanding the concept and mechanism of LLPS and its role in tumorigenesis is crucial for antitumor therapeutic strategies.

Establishment of Transgenic Mouse Leukemia Cell Lines Expressing Human CD4/CCR5/CyclinT1 Infected with HIV-1.

PURPOSE: Establishing a cross-species animal model of human immunodeficiency virus (HIV) infection is crucial for the study of HIV/acquired immunodeficiency syndrome (AIDS). However, due to the species-specific characteristics of HIV-1, the virus can only infect directly humans and a small number of non-human primates. It cannot directly infect mouse cells across species. METHODS: A mouse leukemia cell line with high CD4 (clusters of differentiation 4)/CCR5 (CC-chemokine receptor 5)/CyclinT1 expression was constructed in this study. First, CD4/CCR5/CyclinT1 lentiviral vector was used to infect a murine leukemia cell line L1210 to express the receptor CD4, co-receptor CCR5 and tat protein driving factor CyclinT1, which are required to infect L1210 cells with HIV-1. RESULTS: The results of sequencing identification and fluorescence expression showed that the plasmid expressing CD4, CCR5, and CyclinT1 vector was successfully constructed and wrapped as the lentiviral vector. Moreover, it was observed that CD4, CCR5, and CyclinT1 proteins were highly expressed in mouse leukemia cells L1210 compared to empty lentiviral vector-transfected cells. Next, viral entry and replication were demonstrated when HIV-1 RNA was detected in body cells and cultured supernatants. Transgenic mice cells L1210 showed significantly greater content of HIV-1 RNA compared to control L1210 cells. Finally, CEMx174 was infected with cell culture supernatants to clarify that the progeny virus is an active virus with infection ability. HIV-1 RNA was highly expressed in CEMx174 cells. CONCLUSIONS: This study made the foundation for future studies evaluating HIV-1 cross-species infection in a murine animal model. The results provided new direction for studies investigating the development of vaccines, antiviral drugs screening, and HIV/AIDS pathogenesis.

High-Fructose Diet Induces Cardiac Dysfunction via Macrophage Recruitment in Adult Mice.

Cardiovascular diseases are the leading cause of death globally, including cardiac fibrosis, myocardial infarction, cardiac hypertrophy, and heart failure. High fat/ fructose induces metabolic syndrome, hypertension and obesity, which contributes to cardiac hypertrophy and fibrosis. Excessive fructose intake accelerates inflammation in different organs and tissues, and molecular and cellular mechanisms of organ and tissue injury have been demonstrated. However, the mechanisms of cardiac inflammation have not been fully documented in high-fructose diet. This study shows that there are significantly increased in cardiomyocytes size and relative wall thickness of LV in high-fructose fed adult mice. With echocardiographic analysis of cardiac function, the ejection fraction (EF%) and fractional shortening (FS%) are significantly reduced at 12 weeks after 60% high-fructose diet. The mRNA and protein levels of MCP-1 are notably increased in high-fructose treated HL-1 and primary cardiomyocyte respectively. Also, the increased protein level of MCP-1 has been detected in vivo mouse model after 12 weeks feeding, resulting in the production of pro-inflammatory makers, pro-fibrotic genes expression, and macrophage infiltration. These data demonstrate that high-fructose intake induces cardiac inflammation via macrophage recruitment in cardiomyocyte, which contributes to impair cardiac function.

Modeling Human Brain Tumors and the Microenvironment Using Induced Pluripotent Stem Cells.

Brain cancer is a group of diverse and rapidly growing malignancies that originate in the central nervous system (CNS) and have a poor prognosis. The complexity of brain structure and function makes brain cancer modeling extremely difficult, limiting pathological studies and therapeutic developments. Advancements in human pluripotent stem cell technology have opened a window of opportunity for brain cancer modeling, providing a wealth of customizable methods to simulate the disease in vitro. This is achieved with the advent of genome editing and genetic engineering technologies that can simulate germline and somatic mutations found in human brain tumors. This review investigates induced pluripotent stem cell (iPSC)-based approaches to model human brain cancer. The applications of iPSCs as renewable sources of individual brain cell types, brain organoids, blood-brain barrier (BBB), and brain tumor models are discussed. The brain tumor models reviewed are glioblastoma and medulloblastoma. The iPSC-derived isogenic cells and three-dimensional (3D) brain cancer organoids combined with patient-derived xenografts will enhance future compound screening and drug development for these deadly human brain cancers.

Oral Administration of Artemisia argyi Polysaccharide Increases Estrogen Level and Maintains Blood Lipid Homeostasis in Ovariectomized Rats.

INTRODUCTION: Artemisia argyi polysaccharide (AAP) has a beneficial effect on menstruation-related symptoms and the potential regulation of lipid metabolism. It is expected to be a safe and effective ingredient for estrogen deficiency and lipid metabolic disorders. Here, we investigate the effect of AAP on body weight gain, estrogen level, and blood lipid changes in ovariectomized (OVX) rats. METHODS: Thirty-six female Wistar rats were randomly divided into six treatment groups, including a sham-operated (Sham) group, OVX group, estrogen replacement (OVX + E2) group, and AAP treatment (OVX + 125, 250, 500 mg/kg AAP) group. The body weight and feed intake were recorded every week. The level of estrogen and blood lipid was determined. The gene expressions and protein expressions of estrogen receptors (ERs), fatty acid synthetase (FAS), acetyl CoA carboxylase 2 (ACC2), and 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGR) were determined. RESULTS: AAP treatment significantly decreased the body weight gain and average daily food intake of rats in the OVX group. Treatment with AAP significantly increased the relative weight of the uterus, plasma estrogen level, and the gene expression and protein expression of ER-α in the uterus. For blood lipids, plasma levels of triglyceride, total cholesterol, and low-density lipoprotein cholesterol were significantly reduced by AAP treatment in OVX rats. AAP treatment decreased the expression of FAS and HMGR in the liver of OVX rats. Furthermore, AAP treatment significantly increased the gene expression of ACC2, the protein expression of P-ACC2, and the ratio of P-ACC2/ACC2. CONCLUSION: In summary, AAP treatment exerts beneficial effects on body weight gain and lipid metabolism disorder induced by ovariectomy through increasing estrogen levels, inhibiting FAS, and promoting fatty acid oxidation.

A biotin-stabilized HKUST-1/ADM scaffold for facilitating MSC endothelial differentiation and vascularization in diabetic wound healing.

Inadequate angiogenesis in diabetic wound healing has been identified as one of the most difficult issues to treat. Copper ions (Cu2+) have been confirmed to stimulate angiogenesis; nevertheless, the rapid rise in non-physiological Cu2+ concentrations increases the danger of ion poisoning. For the first time, biotin was used to stabilize a copper-based metal-organic framework (HKUST-1) to change its hydrophobicity and achieve sustained release of Cu2+. The inability to offer a suitable area for the dynamic interaction between cells and growth factors still restricts the use of nanomaterials for the regeneration of injured skin in diabetes. Acellular dermal matrix (ADM) scaffolds are collagen fibers with natural spatial tissue that can create a biological "niche" for cell attachment and growth. In this study, biotin-stabilized HKUST-1 (B-HKUST-1) nanoparticles were modified with an ADM to form a novel scaffold (ADM-B-HKUST-1). Notably, Cu2+ and mesenchymal stem cells (MSCs) released by the composite scaffold may synergistically promote MSC adhesion, proliferation and endothelial differentiation by upregulating the expression of transforming growth factor-ß (TGF-ß), vascular endothelial growth factor (VEGF) and alpha-smooth muscle actin (α-SMA). Overall, the ADM-B-HKUST1 scaffold combines the dual advantages of the sustained release of Cu2+ and creating a biological "niche" can provide a potential strategy for enhancing angiogenesis and promoting diabetic wound healing.

Intratumoral microbiota: implications for cancer onset, progression, and therapy.

Significant advancements have been made in comprehending the interactions between the microbiome and cancer. However, prevailing research predominantly directs its focus toward the gut microbiome, affording limited consideration to the interactions of intratumoral microbiota and tumors. Within the tumor microenvironment (TME), the intratumoral microbiome and its associated products wield regulatory influence, directing the modulation of cancer cell properties and impacting immune system functionality. However, to grasp a more profound insight into the intratumoral microbiota in cancer, further research into its underlying mechanisms is necessary. In this review, we delve into the intricate associations between intratumoral microbiota and cancer, with a specific focus on elucidating the significant contribution of intratumoral microbiota to the onset and advancement of cancer. Notably, we provide a detailed exploration of therapeutic advances facilitated by intratumoral microbiota, offering insights into recent developments in this burgeoning field.

Human Forebrain Organoid-Derived Extracellular Vesicle Labeling with Iron Oxides for In Vitro Magnetic Resonance Imaging.

The significant roles of extracellular vesicles (EVs) as intracellular mediators, disease biomarkers, and therapeutic agents, make them a scientific hotspot. In particular, EVs secreted by human stem cells show significance in treating neurological disorders, such as Alzheimer's disease and ischemic stroke. However, the clinical applications of EVs are limited due to their poor targeting capabilities and low therapeutic efficacies after intravenous administration. Superparamagnetic iron oxide (SPIO) nanoparticles are biocompatible and have been shown to improve the targeting ability of EVs. In particular, ultrasmall SPIO (USPIO, <50 nm) are more suitable for labeling nanoscale EVs due to their small size. In this study, induced forebrain neural progenitor cortical organoids (iNPCo) were differentiated from human induced pluripotent stem cells (iPSCs), and the iNPCo expressed FOXG1, Nkx2.1, α-catenin, as well as ß-tubulin III. EVs were isolated from iNPCo media, then loaded with USPIOs by sonication. Size and concentration of EV particles were measured by nanoparticle tracking analysis, and no significant changes were observed in size distribution before and after sonication, but the concentration decreased after labeling. miR-21 and miR-133b decreased after sonication. Magnetic resonance imaging (MRI) demonstrated contrast visualized for the USPIO labeled EVs embedded in agarose gel phantoms. Upon calculation, USPIO labeled EVs exhibited considerably shorter relaxation times, quantified as T2 and T2* values, reducing the signal intensity and generating higher MRI contrast compared to unlabeled EVs and gel only. Our study demonstrated that USPIO labeling was a feasible approach for in vitro tracking of brain organoid-derived EVs, which paves the way for further in vivo examination.

Overcoming resistance to immune checkpoint inhibitors in hepatocellular carcinoma: Challenges and opportunities.

Hepatocellular carcinoma is one of the leading causes of cancer mortality globally, and its incidence is increasing. Immune checkpoint therapy has revolutionized the treatment of hepatocellular carcinoma over the past few years. However, only a limited proportion of patients with hepatocellular carcinoma respond to immunotherapy. Despite the significant breakthroughs, the molecular mechanisms that drive immune responses and evasion are largely unresolved. Predicting tumor response and resistance to immune checkpoint inhibitors is a significant challenge. In this review, we focus on the current research progress of immune checkpoint inhibitors in hepatocellular carcinoma. Importantly, this review highlights the underlying mechanisms of resistance to immune checkpoint inhibitors and summarizes potential strategies to overcome the resistance to immune checkpoint inhibitors in hepatocellular carcinoma.

An integrative prognostic and immune analysis of PTPRD in cancer.

PTPRD plays an indispensable role in the occurrence of multiple tumors. However, pan-cancer analysis is unavailable. The purpose of this research was to preliminarily study its prognostic landscape across various tumors and investigate its relationship with immunotherapy. We exhibited the expression profile, survival analysis, and genomic alterations of PTPRD based on the TIMER, GEPIA, UALCAN, PrognoScan and cBioPortal database. The frequency of PTPRD mutation and its correlation with response to immunotherapy were evaluated using the cBioPortal database. The relationship between PTPRD and immune-cell infiltration was analyzed by the TIMER and TISIDB databases. A protein interaction network was constructed by the STRING database. GO and KEGG enrichment analysis was executed by the Metascape database. A correlation between PTPRD expression and prognosis was found in various cancers. Aberrant PTPRD expression was closely related to immune infiltration. In non-small cell lung cancer and melanoma, patients with PTPRD mutations had better overall survival with immune checkpoint inhibitors, and these patients had higher TMB scores. PTPRD mutation was involved in numerous biological processes, including immunological signaling pathways. A PTPRD protein interaction network was constructed, and genes that interacted with PTPRD were identified. Functional enrichment analysis demonstrated that a variety of GO biological processes and KEGG pathways associated with PTPRD were involved in the therapeutic mechanisms. These results revealed that PTPRD might function as a biomarker for prognosis and immune infiltration in cancers, throwing new light on cancer therapeutics.