Diagnosis and minimally invasive treatment of type III choledochal cysts.

BACKGROUND: Type III choledochal cysts (CCs) are the rarest and least well-characterized of the five variants of biliary cysts. Only a few relevant studies have been conducted and a gold standard treatment for type III CCs is still lacking because of their scarcity. An unusual case of type III CC with choledochocele at the end of the distal common bile duct (CBD) with no bulging of the duodenum is presented here. CASE PRESENTATION: A 61-year-old woman presented to our department with repeated upper abdominal pain for one year. Laboratory examination revealed abnormal liver function and a slight increase in the white blood cell (WBC) count and proportion of neutrophils. In an MRCP of the patient, the distal CBD was found to have a cystic structure indicative of a type III CC. Endoscopic retrograde cholangiopancreatograpy (ERCP) revealed cystic findings compatible with Todani type III CCs. However, duodenoscopy did not show a bulge in the duodenum so laparoscopic cholecystectomy and Roux-en-Y hepaticojejunostomy were performed. In her 6-month follow-up, the patient reported that recovery from the operation was uneventful. CONCLUSIONS: ERCP has become the gold standard for diagnosing type III CCs. Type III CCs can be treated minimally invasively with laparoscopic cholecystectomy and Roux-en-Y hepaticojejunostomy.

Prognostic Value of E2F Transcription Factor Expression in Pancreatic Adenocarcinoma.

BACKGROUND Pancreatic adenocarcinoma (PAAD) is one of the deadliest types of cancer. In the early stages, patients often have atypical symptoms, making diagnosis difficult. The prognosis of diagnosed patients is very poor and treating PAAD is challenging. Therefore, determining reliable risk factors related to PAAD development is critical for improving patient prognosis. E2F family transcription factors (TFs) are essential regulators of DNA synthesis and cell cycle progression in eukaryotic cells, and they have been identified as prognostic biomarkers associated with multiple cancer types. However, further research is necessary to establish the prognostic relevance of these TFs in PAAD patients. MATERIAL AND METHODS We assessed PAAD patient transcriptional and outcome data using the TIMER, ONCOMINE, STRING, GEPIA, cBioPortal, Kaplan-Meier Plotter, GSCALite, and starBase databases. RESULTS PAAD tumor tissues exhibited increased expression of E2F1/3/5/7/8 relative to that in normal tissues, while the expression of E2F2/3/6/8 was associated with a more advanced tumor stage. Survival analyses indicated that PAAD patients expressing higher levels of E2F1/2/3/7/8 exhibited shorter overall survival (OS) and disease-free survival (DFS) than patients expressing lower levels of these TFs. In addition, E2F4 and E2F6 overexpression was associated with poorer DFS and OS, respectively. We also found that the expression of E2Fs was significantly correlated with immune infiltrates, including CD8+ T cells, CD4+ T cells, B cells, dendritic cells, neutrophils, and macrophages. CONCLUSIONS Our study may provide new insights into the optimal choice of immunotherapy and promising novel targets for therapeutic intervention in PAAD patients.

Study of FABP's interactome and detecting new molecular targets in clear cell renal cell carcinoma.

Fatty acids (FAs) play a crucial role in the development of clear cell renal cell carcinoma (ccRCC), FAs function requires the participation of fatty-acid-binding protein (FABP). Current studies have shown that different members of the FABP's family play different roles in the tumorigenesis of ccRCC. Therefore, the systematic analysis of FABPs will be of great significance. However, the diverse expression patterns and prognostic values of nine FABPs have yet to be elucidated. In this study, through multiple analysis and verification of multiple databases, such as ONCOMINE, The Human Protein Atlas, UALCAN, Gene Expression Profiling Interactive Analysis, and cBioPortal, we found that the expression of FABP1 was significantly downregulated and the expression of FABP5/6/7 was significantly upregulated in ccRCC compared with renal tissues, and the patients with high messenger RNA (mRNA) levels of the FABP5/6/7 or low mRNA levels of FABP1 were predicted to have a lower overall survival or disease-free survival. Further analysis by the protein-protein interaction (PPI), Gene Ontology pathway, and Kyoto Encyclopedia of Genes and Genomes pathway showed that FABPs were mainly involved in the peroxisome proliferator-activated receptor (PPAR) pathway. In coexpression analysis, we found that FABP1/5/6/7 was coexpressed with transforming growth factor-ß1 (TGF-ß1), PPARA, and LPL. This study implied that FABP1/5/6/7 could act as an important tumor biomarker of ccRCC; the role of FABPs may be related to PPAR or TGF-ß pathway.

Tripartite-motif family genes associated with cancer stem cells affect tumor progression and can assist in the clinical prognosis of kidney renal clear cell carcinoma.

Ubiquitination is presently a hot topic in the field of oncology. The tripartite-motif (TRIM) family of proteins represents one of the largest classes of putative single protein RING-finger E3 ubiquitin ligases, which play an essential role in the ubiquitination of proteins in the body. At the same time, research related to cancer stem cells (CSCs) is increasing in popularity in the field of oncology. CSCs are potentially chemically resistant and can be selectively enriched in patients receiving chemotherapy, ultimately leading to adverse outcomes, such as treatment failure and cancer recurrence. There is a close relationship between multiple TRIM family genes and CSCs. Accumulating evidence suggests that TRIM family proteins are expressed in diverse human cancers and act as regulators of oncoproteins or tumor suppressor proteins. In this study, we used biological information to explore the potential function of TRIM family genes related to CSCs in the development of pan-cancer. Kidney renal clear cell carcinoma (KIRC) is one of the deadliest malignant tumors in the world. Owing to its complex molecular and cellular heterogeneity, the effectiveness of existing KIRC-related risk prediction models is not satisfactory at present. Therefore, we focused on the potential role of these TRIM family genes in KIRC and used seven TRIM family genes to establish a prognostic risk model. This model includes TRIM16, TRIM32, TRIM24, TRIM8, TRIM27, PML, and TRIM11. In conclusion, this study provides further insight into the prognosis of KIRC, which may guide treatment.

Statin use and the overall survival of renal cell carcinoma: A meta-analysis.

PURPOSE: Statins are commonly prescribed drugs that reduce cholesterol levels and the risk of cardiovascular and cerebrovascular events. Clinical studies have shown that statins also possess cancer-preventive properties. Two studies have reported that statins also possess cancer-preventive properties; however, whether statins improve the prognosis of patients with renal cell carcinoma is still unclear. In this study, we used meta-analysis to evaluate the association between statin use and overall survival risk in patients with renal cell carcinoma. METHODS: Published studies on statin-treated renal cell carcinoma were retrieved from PubMed, Embase, The Cochrane Library, China National Knowledge Infrastructure and Wanfang databases from inception to July 2019. The relevant data were extracted and a meta-analysis was performed using Cochrane Review Manager (RevMan 5.3) software. RESULTS: Data from five studies, which reported on 5,299 patients, were analysed. The application of statins showed no effects on the overall survival of patients with renal cell carcinoma compared with the control group (OR = 1.07, 95% CI:0.77 to 1.49, P = 0.68). CONCLUSIONS: The findings of this meta-analysis suggest that statin application does not affect the overall survival of patients with renal cell carcinoma.

Sorafenib induces renal cell carcinoma apoptosis via upregulating activating transcription factor 4.

Previous studies have shown sorafenib to function as a multitargeted tyrosine kinase inhibitor in different tumors. However, whether sorafenib improves renal cell carcinoma (RCC) through activating transcription factor 4 (ATF4) has never been explored. In the current study, we showed that sorafenib could suppress RCC cell viability in a time- and dose-dependent manner. Furthermore, sorafenib is demonstrated to enhance the mRNA and protein levels of ATF4. Meanwhile, overexpression of ATF4 was demonstrated to induce ACHN cell cycle arrest and cell apoptosis. Moreover, treatment with sorafenib could enhance the expression of CCAAT/enhancer-binding protein-homologous protein (CHOP) and p53 upregulated modulator of apoptosis (PUMA), thereby leading to ACHN cell apoptosis. More importantly, silencing of ATF4 could largely abolish sorafenib-induced upregulation of CHOP and PUMA in ACHN cells. Meanwhile, sorafenib-induced cell apoptosis may be dependent on the activation of ATF4 since knockdown of ATF4 partially reversed sorafenib-induced ACHN cell apoptosis. In summary, the present study demonstrates that sorafenib activates ATF4-CHOP-PUMA pathway in RCC cells, resulting in enhanced ER stress-related cell apoptosis.

Deciphering the role of neddylation in tumor microenvironment modulation: common outcome of multiple signaling pathways.

Neddylation is a post-translational modification process, similar to ubiquitination, that controls several biological processes. Notably, it is often aberrantly activated in neoplasms and plays a critical role in the intricate dynamics of the tumor microenvironment (TME). This regulatory influence of neddylation permeates extensively and profoundly within the TME, affecting the behavior of tumor cells, immune cells, angiogenesis, and the extracellular matrix. Usually, neddylation promotes tumor progression towards increased malignancy. In this review, we highlight the latest understanding of the intricate molecular mechanisms that target neddylation to modulate the TME by affecting various signaling pathways. There is emerging evidence that the targeted disruption of the neddylation modification process, specifically the inhibition of cullin-RING ligases (CRLs) functionality, presents a promising avenue for targeted therapy. MLN4924, a small-molecule inhibitor of the neddylation pathway, precisely targets the neural precursor cell-expressed developmentally downregulated protein 8 activating enzyme (NAE). In recent years, significant advancements have been made in the field of neddylation modification therapy, particularly the integration of MLN4924 with chemotherapy or targeted therapy. This combined approach has demonstrated notable success in the treatment of a variety of hematological and solid tumors. Here, we investigated the inhibitory effects of MLN4924 on neddylation and summarized the current therapeutic outcomes of MLN4924 against various tumors. In conclusion, this review provides a comprehensive, up-to-date, and thorough overview of neddylation modifications, and offers insight into the critical importance of this cellular process in tumorigenesis.

Frontiers in sarcopenia: Advancements in diagnostics, molecular mechanisms, and therapeutic strategies.

The onset of sarcopenia is intimately linked with aging, posing significant implications not only for individual patient quality of life but also for the broader societal healthcare framework. Early and accurate identification of sarcopenia and a comprehensive understanding of its mechanistic underpinnings and therapeutic targets paramount to addressing this condition effectively. This review endeavors to present a cohesive overview of recent advancements in sarcopenia research and diagnosis. We initially delve into the contemporary diagnostic criteria, specifically referencing the European Working Group on Sarcopenia in Older People (EWGSOP) 2 and Asian Working Group on Sarcopenia (AWGS) 2019 benchmarks. Additionally, we elucidate comprehensive assessment techniques for muscle strength, quantity, and physical performance, highlighting tools such as grip strength, chair stand test, dual-energy X-ray Absorptiometry (DEXA), bioelectrical impedance analysis (BIA), gait speed, and short physical performance battery (SPPB), while also discussing their inherent advantages and limitations. Such diagnostic advancements pave the way for early identification and unequivocal diagnosis of sarcopenia. Proceeding further, we provide a deep-dive into sarcopenia's pathogenesis, offering a thorough examination of associated signaling pathways like the Myostatin, AMP-activated protein kinase (AMPK), insulin/IGF-1 Signaling (IIS), and the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways. Each pathway's role in sarcopenia mediation is detailed, underscoring potential therapeutic target avenues. From a mechanistic perspective, the review also underscores the pivotal role of mitochondrial dysfunction in sarcopenia, emphasizing elements such as mitochondrial oxidative overload, mitochondrial biogenesis, and mitophagy, and highlighting their therapeutic significance. At last, we capture recent strides made in sarcopenia treatment, ranging from nutritional and exercise interventions to potential pharmacological and supplementation strategies. In sum, this review meticulously synthesizes the latest scientific developments in sarcopenia, aiming to enhance diagnostic precision in clinical practice and provide comprehensive insights into refined mechanistic targets and innovative therapeutic interventions, ultimately contributing to optimized patient care and advancements in the field.

The potential value of the Purinergic pathway in the prognostic assessment and clinical application of kidney renal clear cell carcinoma.

The Purinergic pathway is involved in a variety of important physiological processes in living organisms, and previous studies have shown that aberrant expression of the Purinergic pathway may contribute to the development of a variety of cancers, including kidney renal clear cell carcinoma (KIRC). The aim of this study was to delve into the Purinergic pathway in KIRC and to investigate its potential significance in prognostic assessment and clinical treatment. 33 genes associated with the Purinergic pathway were selected for pan-cancer analysis. Cluster analysis, targeted drug sensitivity analysis and immune cell infiltration analysis were applied to explore the mechanism of Purinergic pathway in KIRC. Using the machine learning process, we found that combining the Lasso+survivalSVM algorithm worked well for predicting survival accuracy in KIRC. We used LASSO regression to pinpoint nine Purinergic genes closely linked to KIRC, using them to create a survival model for KIRC. ROC survival curve was analyzed, and this survival model could effectively predict the survival rate of KIRC patients in the next 5, 7 and 10 years. Further univariate and multivariate Cox regression analyses revealed that age, grading, staging, and risk scores of KIRC patients were significantly associated with their prognostic survival and were identified as independent risk factors for prognosis. The nomogram tool developed through this study can help physicians accurately assess patient prognosis and provide guidance for developing treatment plans. The results of this study may bring new ideas for optimizing the prognostic assessment and therapeutic approaches for KIRC patients.

Evaluating the Role of Neddylation Modifications in Kidney Renal Clear Cell Carcinoma: An Integrated Approach Using Bioinformatics, MLN4924 Dosing Experiments, and RNA Sequencing.

BACKGROUND: Neddylation, a post-translational modification process, plays a crucial role in various human neoplasms. However, its connection with kidney renal clear cell carcinoma (KIRC) remains under-researched. METHODS: We validated the Gene Set Cancer Analysis Lite (GSCALite) platform against The Cancer Genome Atlas (TCGA) database, analyzing 33 cancer types and their link with 17 neddylation-related genes. This included examining copy number variations (CNVs), single nucleotide variations (SNVs), mRNA expression, cellular pathway involvement, and methylation. Using Gene Set Variation Analysis (GSVA), we categorized these genes into three clusters and examined their impact on KIRC patient prognosis, drug responses, immune infiltration, and oncogenic pathways. Afterward, our objective is to identify genes that exhibit overexpression in KIRC and are associated with an adverse prognosis. After pinpointing the specific target gene, we used the specific inhibitor MLN4924 to inhibit the neddylation pathway to conduct RNA sequencing and related in vitro experiments to verify and study the specificity and potential mechanisms related to the target. This approach is geared towards enhancing our understanding of the prognostic importance of neddylation modification in KIRC. RESULTS: We identified significant CNV, SNV, and methylation events in neddylation-related genes across various cancers, with notably higher expression levels observed in KIRC. Cluster analysis revealed a potential trade-off in the interactions among neddylation-related genes, where both high and low levels of gene expression are linked to adverse prognoses. This association is particularly pronounced concerning lymph node involvement, T stage classification, and Fustat score. Simultaneously, our research discovered that PSMB10 exhibits overexpression in KIRC when compared to normal tissues, negatively impacting patient prognosis. Through RNA sequencing and in vitro assays, we confirmed that the inhibition of neddylation modification could play a role in the regulation of various signaling pathways, thereby influencing the prognosis of KIRC. Moreover, our results underscore PSMB10 as a viable target for therapeutic intervention in KIRC, opening up novel pathways for the development of targeted treatment strategies. CONCLUSION: This study underscores the regulatory function and potential mechanism of neddylation modification on the phenotype of KIRC, identifying PSMB10 as a key regulatory target with a significant role in influencing the prognosis of KIRC.

Erratum: The potential value of cuprotosis (copper-induced cell death) in the therapy of clear cell renal cell carcinoma.

[This corrects the article on p. 3947 in vol. 12, PMID: 36119838.].

The utilization of single-cell sequencing technology in investigating the immune microenvironment of ccRCC.

The growth and advancement of ccRCC are strongly associated with the presence of immune infiltration and the tumor microenvironment, comprising tumor cells, immune cells, stromal cells, vascular cells, myeloid-derived cells, and extracellular matrix (ECM). Nevertheless, as a result of the diverse and constantly evolving characteristics of the tumor microenvironment, prior advanced sequencing methods have frequently disregarded specific less prevalent cellular traits at varying intervals, thereby concealing their significance. The advancement and widespread use of single-cell sequencing technology enable us to comprehend the source of individual tumor cells and the characteristics of a greater number of individual cells. This, in turn, minimizes the impact of intercellular heterogeneity and temporal heterogeneity of the same cell on experimental outcomes. This review examines the attributes of the tumor microenvironment in ccRCC and provides an overview of the progress made in single-cell sequencing technology and its particular uses in the current focus of immune infiltration in ccRCC.

Potential effects of gut microbiota on host cancers: focus on immunity, DNA damage, cellular pathways, and anticancer therapy.

The symbiotic bacteria that live in the human gut and the metabolites they produce have long influenced local and systemic physiological and pathological processes of the host. The gut microbiota are increasingly being recognized for its impact on a range of human diseases, including cancer, it may play a key role in the occurrence, progression, treatment, and prognosis of many types of cancer. Understanding the functional role of the gut microbiota in cancer is crucial for the development of the era of personalized medicine. Here, we review recent advances in research and summarize the important associations and clear experimental evidence for the role of the gut microbiota in a variety of human cancers, focus on the application and possible challenges associated with the gut microbiota in antitumor therapy. In conclusion, our research demonstrated the multifaceted mechanisms of gut microbiota affecting human cancer and provides directions and ideas for future clinical research.

Role of NF-κB pathway in kidney renal clear cell carcinoma and its potential therapeutic implications.

Kidney renal clear cell carcinoma (KIRC), a common malignant tumor of the urinary system, is the most aggressive renal tumor subtype. Since the discovery of nuclear factor kappa B (NF-κB) in 1986, many studies have demonstrated abnormal NF-κB signaling is associated with the development of various cancers, including kidney renal clear cell carcinoma. In this study, the relationship between NF-κB and kidney renal clear cell carcinoma was confirmed using bioinformatics analysis. First, we explored the differential expression of copy number variation (CNV), single nucleotide variant (SNV), and messenger RNA (mRNA) in NF-κB-related genes in different types of cancer, as well as the impact on cancer prognosis and sensitivity to common chemotherapy drugs. Then, we divided the mRNA expression levels of NF-κB-related genes in KIRC patients into three groups through GSVA cluster analysis and explored the correlation between the NF-κB pathway and clinical data of KIRC patients, classical cancer-related genes, common anticancer drug responsiveness, and immune cell infiltration. Finally, 11 tumor-related genes were screened using least absolute shrinkage and selection operator (LASSO) regression to construct a prognostic model. In addition, we used the UALCAN and HPA databases to verify the protein levels of three key NF-κB-related genes (CHUK, IKGGB, and IKBKG) in KIRC. In conclusion, our study established a prognostic survival model based on NF-κB-related genes, which can be used to predict the prognosis of patients with KIRC.

Advances in early detection methods for solid tumors.

During the last decade, non-invasive methods such as liquid biopsy have slowly replaced traditional imaging and invasive pathological methods used to diagnose and monitor cancer. Improvements in the available detection methods have enabled the early screening and diagnosis of solid tumors. In addition, advances in early detection methods have made the continuous monitoring of tumor progression using repeat sampling possible. Previously, the focus of liquid biopsy techniques included the following: 1) the isolation of circulating tumor cells, circulating tumor DNA, and extracellular tumor vesicles from solid tumor cells in the patient's blood; in addition to 2) analyzing genomic and proteomic data contained within the isolates. Recently, there has been a rapid devolvement in the techniques used to isolate and analyze molecular markers. This rapid evolvement in detection techniques improves their accuracy, especially when few samples are available. In addition, there is a tremendous expansion in the acquisition of samples and targets for testing; solid tumors can be detected from blood and other body fluids. Test objects have also expanded from samples taken directly from cancer to include indirect objects affected in cancer development. Liquid biopsy technology has limitations. Even so, this detection technique is the key to a new phase of oncogenetics. This review aims to provide an overview of the current advances in liquid biopsy marker selection, isolation, and detection methods for solid tumors. The advantages and disadvantages of liquid biopsy technology will also be explored.

LincRNA PRNCR1 activates the Wnt/ß-catenin pathway to drive the deterioration of hepatocellular carcinoma via regulating miR-411-3p/ZEB1 axis.

Hepatocellular carcinoma (HCC) is an intractable malignant disease with high incidence rate annually. LincRNA PRNCR1 has been confirmed as a tumor supporter, while its functions in HCC remain unclear. This study aims to explore the mechanism of LincRNA PRNCR1 in hepatocellular carcinoma. The qRT-PCR was applied to the quantification of non-coding RNAs. Cell counting Kit-8 (CCK-8), Transwell assay and flow cytometry assay were applied to reflect the change in the phenotype of HCC cells. Moreover, the databases including Targetscan and Starbase and dual-luciferase reporter assay were applied to investigate the interaction of the genes. The western blot was applied to detect the abundance of proteins and the activity of the related pathways. Elevated LincRNA PRNCR1 was dramatically upregulated in HCC pathological samples and cell lines. MiR-411-3p served as a target of LincRNA PRNCR1, and decreased miR-411-3p was found in the clinical samples and cell lines. LincRNA PRNCR1 downregulation could induce the expression of miR-411-3p, and LincRNA PRNCR1 silence could impede the malignant behaviors via increasing the abundance of miR-411-3p. Zinc finger E-box binding homeobox 1 (ZEB1) was confirmed as a target of miR-411-3p, which remarkably upregulated in HCC cells, and ZEB1 upregulation could significantly rescue the effect of miR-411-3p on malignant behaviors of HCC cells. Moreover, LincRNA PRNCR1 was confirmed to involve the Wnt/ß-catenin pathway via regulating miR-411-3p/ZEB1 axis. This study suggested that LincRNA PRNCR1 could drive the malignant progression of HCC via regulating miR-411-3p/ZEB1 axis.

The mechanism and clinical application of DNA damage repair inhibitors combined with immune checkpoint inhibitors in the treatment of urologic cancer.

Urologic cancers such as kidney, bladder, prostate, and uroepithelial cancers have recently become a considerable global health burden, and the response to immunotherapy is limited due to immune escape and immune resistance. Therefore, it is crucial to find appropriate and effective combination therapies to improve the sensitivity of patients to immunotherapy. DNA damage repair inhibitors can enhance the immunogenicity of tumor cells by increasing tumor mutational burden and neoantigen expression, activating immune-related signaling pathways, regulating PD-L1 expression, and reversing the immunosuppressive tumor microenvironment to activate the immune system and enhance the efficacy of immunotherapy. Based on promising experimental results from preclinical studies, many clinical trials combining DNA damage repair inhibitors (e.g., PARP inhibitors and ATR inhibitors) with immune checkpoint inhibitors (e.g., PD-1/PD-L1 inhibitors) are underway in patients with urologic cancers. Results from several clinical trials have shown that the combination of DNA damage repair inhibitors with immune checkpoint inhibitors can improve objective rates, progression-free survival, and overall survival (OS) in patients with urologic tumors, especially in patients with defective DNA damage repair genes or a high mutational load. In this review, we present the results of preclinical and clinical trials of different DNA damage repair inhibitors in combination with immune checkpoint inhibitors in urologic cancers and summarize the potential mechanism of action of the combination therapy. Finally, we also discuss the challenges of dose toxicity, biomarker selection, drug tolerance, drug interactions in the treatment of urologic tumors with this combination therapy and look into the future direction of this combination therapy.

Regulatory roles of ferroptosis-related non-coding RNAs and their research progress in urological malignancies.

Ferroptosis is a new type of cell death characterized by damage to the intracellular microenvironment, which causes the accumulation of lipid hydroperoxide and reactive oxygen species to cause cytotoxicity and regulated cell death. Non-coding RNAs (ncRNAs) play an important role in gene expression at the epigenetic, transcriptional, and post-transcriptional levels through interactions with different DNAs, RNAs, or proteins. Increasing evidence has shown that ferroptosis-related ncRNAs are closely related to the occurrence and progression of several diseases, including urological malignancies. Recently, the role of ferroptosis-associated ncRNAs (long non-coding RNAs, micro RNAs, and circular RNAs) in the occurrence, drug resistance, and prognosis of urological malignancies has attracted widespread attention. However, this has not yet been addressed systematically. In this review, we discuss this issue as much as possible to expand the knowledge and understanding of urological malignancies to provide new ideas for exploring the diagnosis and treatment of urological malignancies in the future. Furthermore, we propose some challenges in the clinical application of ferroptosis-associated ncRNAs.

Tumor Vaccines: Unleashing the Power of the Immune System to Fight Cancer.

This comprehensive review delves into the rapidly evolving arena of cancer vaccines. Initially, we examine the intricate constitution of the tumor microenvironment (TME), a dynamic factor that significantly influences tumor heterogeneity. Current research trends focusing on harnessing the TME for effective tumor vaccine treatments are also discussed. We then provide a detailed overview of the current state of research concerning tumor immunity and the mechanisms of tumor vaccines, describing the complex immunological processes involved. Furthermore, we conduct an exhaustive analysis of the contemporary research landscape of tumor vaccines, with a particular focus on peptide vaccines, DNA/RNA-based vaccines, viral-vector-based vaccines, dendritic-cell-based vaccines, and whole-cell-based vaccines. We analyze and summarize these categories of tumor vaccines, highlighting their individual advantages, limitations, and the factors influencing their effectiveness. In our survey of each category, we summarize commonly used tumor vaccines, aiming to provide readers with a more comprehensive understanding of the current state of tumor vaccine research. We then delve into an innovative strategy combining cancer vaccines with other therapies. By studying the effects of combining tumor vaccines with immune checkpoint inhibitors, radiotherapy, chemotherapy, targeted therapy, and oncolytic virotherapy, we establish that this approach can enhance overall treatment efficacy and offset the limitations of single-treatment approaches, offering patients more effective treatment options. Following this, we undertake a meticulous analysis of the entire process of personalized cancer vaccines, elucidating the intricate process from design, through research and production, to clinical application, thus helping readers gain a thorough understanding of its complexities. In conclusion, our exploration of tumor vaccines in this review aims to highlight their promising potential in cancer treatment. As research in this field continues to evolve, it undeniably holds immense promise for improving cancer patient outcomes.

Potential value of mitochondrial regulatory pathways in the clinical application of clear cell renal cell carcinoma: a machine learning-based study.

BACKGROUND: Renal clear cell carcinoma (RCC) is a common cancer in urinary system with increasing incidence. At present, targeted therapy and immunotherapy are the main therapeutic programs in clinical therapy. To develop novel drugs and provide new ideas for clinical therapy, the identification of potential ccRCC subtypes and potential target genes or pathways has become a current research focus. AIM: The aim of this study was to explore the underlying mechanisms of mitochondrial function in ccRCC. This regulatory pathway is closely related to tumor development and metastasis in ccRCC patients, and their abnormal changes may affect the prognosis of cancer patients. Therefore, we decided to construct a prognostic model of ccRCC patients based on mitochondrial regulatory genes, aiming to provide new methods and ideas for clinical therapy. RESULT: The 5-year survival prediction model based on iterative LASSO reached 0.746, and the cox model based on coxph reached C-index = 0.77, integrated c/D AUC = 0.61, and integrated brier score = 0.14. The rsf model based on randomForestSRC was built with C-index = 0.82, integrated c/D AUC = 0.69, and integrated brier score = 0.11. The results show that mitochondrial regulatory pathway is a potential target pathway for clinical therapy of ccRCC, which can provide guidelines for clinical targeted therapy, immunotherapy and other first-line therapy.