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A comprehensive understanding of tumor heterogeneity, tumor microenvironment and the mechanisms of drug resistance is fundamental to advancing breast cancer research. While single-cell RNA sequencing has resolved the issue of “temporal dynamic expression” of genes at the single-cell level, the lack of spatial information still prevents us from gaining a comprehensive understanding of breast cancer. The introduction and application of spatial transcriptomics addresses this limitation. As the annual technical method of 2020, spatial transcriptomics preserves the spatial location of tissues and resolves RNA-seq data to help localize and differentiate the active expression of functional genes within a specific tissue region, enabling the study of spatial location attributes of gene locations and cellular tissue environments. In the context of breast cancer, spatial transcriptomics can assist in the identification of novel breast cancer subtypes and spatially discriminative features that show promise for individualized precise treatment. This article summarized the key technical approaches, recent advances in spatial transcriptomics and its applications in breast cancer, and discusses the limitations of current spatial transcriptomics methods and the prospects for future development, with a view to advancing the application of this technology in clinical practice.

Abstract Circular RNAs (circRNAs) are linked to cancer, but it's still not clear what role they play in prostatic cancer. Through high-throughput sequencing, the goal of this study was to compare how circRNAs are expressed at different stages of prostate cancer. 12 patients attending the Department of Urology at the Second Affiliated Hospital of Nanchang University between June 2020 and October 2021 were used for RNA sequencing, and 14 patients were used for real-time fluorescent quantitative PCR (qRT-PCR). The expression profiles of prostate cancer circRNAs were constructed by sequencing with the help of next-generation high-throughput sequencing technology, and the differentially expressed circRNAs were analyzed by targeting microRNA (miRNA) loci and Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the genes from which circRNAs originated. Finally, the expression of target circRNAs in two prostate tissues was verified by qRT-PCR. Following high-throughput sequencing, 13,047 circRNAs were identified, and 605 circRNAs with significant differential expression were identified, of which 361 circRNAs were up-regulated, and 244 circRNAs were down-regulated. Analysis of circRNA-originated genes using GO and the KEGG enrichment analysis showed that circRNA host genes can regulate and influence multiple signaling pathways in prostate cancer with important biological functions. And the circRNA–miRNA network was constructed. The highest number of differentially expressed circRNA-binding miRNAs were: hsa_circ_000 7582 (52), hsa_circ_000 6198 (37), hsa_circ_000 6759 (28), hsa_circ_000 5675 (25), and hsa_circ_000 2172 (22). Moreover, we further screened out the circRNA (hsa_circ_0005692) that was significantly differentially expressed and common to all groups and verified by qRT-PCR that the expression of the target circRNA (hsa_circ_0005692) was significantly downregulated in prostate cancer compared with benign prostatic hyperplasia (BPH) tissues.

Abstract Signal transducer and activator of transcription 4 (STAT4) is a critical transcription factor for T helper cell differentiation and tumor cells. Although its prognostic role and gene function have been reported in several carcinomas, the role of STAT4 in vitro and in vivo in breast cancer remains poorly understood. The effect of STAT4 in immunotherapy is also unclear. Therefore, we integrated bulk transcriptomics, experiments, and single‐cell transcriptomics to systematically analyze its function in prognosis and signaling pathway. Several clinical breast cancer cohorts confirmed STAT4 as a T‐cell relevant prognostic biomarker. Overexpressed STAT4 increased programmed cell death ligand 1 (PD‐L1) and major histocompatibility complex class II levels in breast cancer cells. In molecular mechanism, transcriptional synergy between STAT4 and STAT3 transactivated interleukin (IL)‐12R and involved a positive feedback loop: STAT4/IL‐12R/JAK2–STAT3–STAT4, which contributed to the upregulation of PD‐L1 expression. The above signaling axis was defined as the STAT4‐related pathway and its score was used to predict T‐cell expansion and anti‐PD1 treatment response. These findings highlight a novel molecular mechanism indirectly regulating PD‐L1 through the STAT4‐related pathway: IL‐12R/JAK2–STAT3–STAT4/PD‐L1, and it has potential application in predicting anti‐PD‐1 immunotherapy response, which may pave the way for stratified immunotherapy in breast cancer.

Abstract Renal cell carcinoma (RCC) seriously threatens people's lives and health. The identification of some precise biomarkers during the process of RCC progression and the pathophysiologic procedure is critical for improving the diagnosis and management of RCC. Evidence suggests that ferroptosis may play a pivotal role in eradicating clear cell RCC (ccRCC, KIRC) tumor cells. We screened out the target prognostic ferroptosis‐associated genes and examined the functions of farnesyl‐diphosphate farnesyltransferase (FDFT1) in 786‐O cells by plasmid transfection. In our study, we identified FDFT1 as a potential marker correlating with ferroptosis in KIRC. Upregulated FDFT1 inhibited cell proliferation, migration, and invasion, and the underlying antitumor effects may occur via the AKT signaling pathway. Our study provides helpful evidence to study the complex physiopathology of KIRC.

Conventional therapy for kidney renal clear cell carcinoma (KIRC) is unpromising. The tumor microenvironment (TME) is intimately linked to the invasiveness of a variety of tumor forms, including KIRC. The purpose of this research is to establish the prognostic and immune-related significance of dihydrolipoamide branched chain transacylase E2 (DBT) in individuals with KIRC. In this investigation, we discovered that DBT expression was down-regulated in a range of human malignancies, and low DBT expression in KIRC was linked to higher-level clinicopathological characteristics as well as a poor prognosis for KIRC patients. Based on the findings of univariate and multivariate Cox regression analyses, DBT might be employed as an independent prognostic factor in KIRC patients. Furthermore, we developed a nomogram to better investigate DBT’s predictive usefulness. To confirm DBT expression, we examined KIRC cell lines using RT-qPCR and Western blotting. We also examined the role of DBT in KIRC using colony formation, CCK-8, EdU, transwell, and wound healing assays. We discovered that plasmid-mediated overexpression of DBT in KIRC cells slowed cell proliferation and decreased migration and invasion. Multiple enrichment analyses revealed that DBT may be involved in processes and pathways related to immunotherapy and drug metabolism. We computed the immune infiltration score and discovered that the immunological score and the ESTIMATE score were both greater in the DBT low expression group. According to the CIBERSORT algorithm, DBT seems to promote anti-cancer immune responses in KIRC by activating M1 macrophages, mast cells, and dendritic cells while inhibiting regulatory T cells. Finally, in KIRC, DBT expression was found to be highly linked to immunological checkpoints, targeted medicines, and immunotherapeutic agents. Our findings suggest that DBT is a distinct predictive biomarker for KIRC patients, playing a significant role in the TME of KIRC and serving as a reference for the selection of targeted treatment and immunotherapy.

We reported a case of pure laparoscopic radical nephroureterectomy for complicated renal pelvis carcinoma combined with horseshoe kidney (HSK). The aim was to present a case report and review of the literature about renal pelvis carcinoma combined with HSK. The case report includes a history of patient data. The pure laparoscopic radical nephroureterectomy was provided with the informed consent of the patient. A 53-year-old patient was diagnosed with a right renal pelvis mass with HSK. We performed laparoscopic radical nephroureterectomy with partial cystectomy and horseshoe renal isthmus amputation. Histopathological features, computed tomography urography (CTU), and angiography (CTA) confirmed the diagnosis of renal pelvis carcinoma combined with HSK. The tumor was removed, and the patient had an uneventful recovery. Renal pelvis carcinoma combined with HSK is a rare case. Due to severe anatomical abnormalities, this disease is a major challenge for urologists. We share our successful case for readers to learn from.

Cuproptosis is a novel kind of programmed cell death that has been linked to tumor development, prognosis, and responsiveness to therapy. Nevertheless, the precise function of cuproptosis-related genes (CRGs) in the tumor microenvironment (TME) remains unknown. We characterized the genetic and transcriptional changes of CRGs in papillary renal cell carcinoma (PRCC) samples and analyzed the expression patterns in two separate cohorts. We observed that two unique cuproptosis-related subgroups and three separate gene subgroups were connected with clinicopathological, prognostic, and TME features of patients. Then, a risk score for predicting overall survival (OS) was created and validated in patients with PRCC. To make the risk score more clinically useful, we created a nomogram that was very accurate. A lower risk score, which was associated with higher tumor mutation burden, and immune activity, suggested a better prognosis for OS. Additionally, the risk score was shown to be substantially linked with the drug’s susceptibility to chemotherapeutic agents. Our extensive research of CRGs in PRCC identified possible roles for them in the TME, clinicopathological features, and overall survival. These findings may help advance our knowledge of CRGs in PRCC and pave the way for improved prognosis and the creation of more effective immunotherapy therapies.

ObjectiveLong-chain acyl-coenzyme A synthases (ACSLs) catalyze the activation of fatty acid and are often dysregulated in malignancies. The purpose of this research was to figure out the ACSL3's prognostic value and mechanism in clear cell renal cell carcinoma (ccRCC).MethodsThe expression of ACSL3 in ccRCC was investigated in this work using data from the GEO, TCGA, Oncomine and HPA databases. The expression differences of ACSL3 in the cell lines were further detected by qPCR and Western blot. GEPIA, MethSurv, cBioPortal, and the TIMER were used to perform survival and correlation analysis on ACSL3. GO and KEGG analyses were carried out in R using clusterProfiler and GOplot. Protein-protein interactions (PPI) are constructed from Strings website, and the results were visualized in Cytoscape software.ResultsThe expression level of ACSL3 was significantly reduced in ccRCC tissues, and its mRNA and protein expression were also significantly lower in both renal cancer cell lines. ACSL3 is significantly related to clinical stage, OS, DFS, DNA methylation, and immune-cell infiltration.ConclusionOur findings demonstrated that data mining was capable of eliciting information on ACSL3 levels and its role in genetic regulatory pathways in ccRCC.

Background: Immunotherapy has emerged as an important technique for treating a variety of cancers. The dynamic interplay between tumor cells and invading lymphocytes in the tumor microenvironment is responsible for the good response to immunotherapy (TME). Pyroptosis, or inflammation-induced cell death, is closely linked to a number of cancers. However, in papillary renal cell carcinoma (KIRP), the association between pyroptosis and clinical prognosis, immune cell infiltration, and immunotherapy impact remains unknown.Methods: We carefully investigated the link between pyroptosis and tumor growth, prognosis, and immune cell infiltration by evaluating 52 pyroptosis-related genes. The PRG score was utilized to measure a single tumor patient’s pyroptosis pattern. After that, we looked at how well these values predicted prognoses and therapy responses in KIRP.Results: We discovered that PRG differences between subgroups were linked to clinical and pathological aspects, prognosis, and TME in two separate genetic subtypes. After that, a PRG score for estimating overall survival (OS) was developed, and its predictive potential in KIRP patients was confirmed. As a result, we developed a very precise nomogram to improve the PRG score’s clinical usefulness. A low PRG score, which is determined by mutation load and immune activation, suggests a good chance of survival. Furthermore, the PRG score was linked to chemotherapeutic drug sensitivity in a substantial way.Conclusions: The possible functions of PRGs in the TME, clinical and pathological characteristics, and prognosis were established in our thorough investigation of PRGs in KIRP. These results might help us better understand PRGs in KIRP and offer a new avenue for prognostic evaluation and the development of more effective immunotherapy treatments.

Renal ischemia-reperfusion injury (IRI) is considered as a major cause of acute kidney injury. In this study, we investigated the role of the NF-κB signaling pathway and inflammation in the amelioration of renal IRI using pioglitazone. Sprague–Dawley (SD) rats were subjected to bilateral renal artery clamping for 45 min followed by perfusion restoration for establishing a simulated renal IRI model. At 24 h post-operatively, we assessed the serum levels of creatinine and urea nitrogen, expression levels of peroxisome proliferator-activated receptor gamma (PPAR-γ) and NF-κB-related (p-IKK-β and IκB-α) proteins, and mRNA expression levels of the inflammatory cytokines, including TNF-α and MCP-1, in the renal tissue of various study groups. The histopathological evaluation of renal tissue was also conducted. In rat renal tissue, pioglitazone treatment decreased the serum levels of post-renal IRI creatinine and urea nitrogen, as well as necrosis. Furthermore, it elevated the expression of PPAR-γ protein and decreased the expression of NF-κB-related proteins. Pioglitazone also decreased the mRNA expression of TNF-α and MCP-1 in the renal tissue. Thus, pioglitazone ameliorates renal IRI by inhibiting the NF-κB signaling pathway and inflammatory response in rats.

ObjectiveThe choice of surgical method for clinically diagnosed T2 or higher stage kidney cancer remains controversial. Here, we systematically reviewed and collected published comparative studies on renal function, oncologic outcomes, and perioperative results of partial nephrectomy (PN) versus radical nephrectomy (RN) for larger renal tumors (T2 and above), and performed a meta-analysis.Evidence AcquisitionFollowing searches of PubMed, Web of Science, and Embase, the original studies on PN vs. RN in the treatment of T2 renal cancer were screened through strict inclusion and exclusion criteria. RevMan 5.4 was used for data analysis of the perioperative results, renal function, and oncologic outcomes of the two surgical methods for T2 renal tumor therapy. The weighted mean difference was used as the combined effect size for continuous variables, while the odds ratio (OR) or risk ratio (RR) was used as the combined effect size for binary variables. Both variables used a 95% confidence interval (CI) to estimate statistical accuracy. In cases with low heterogeneity, the fixed-effects model was used to pool the estimated value; otherwise, the random-effects model was used when significant heterogeneity was detected.ResultsFifteen retrospective studies including 5,056 patients who underwent nephrectomy (PN: 1975, RN: 3081) were included. The decline in estimated GFR (eGFR) after PN was lower than RN [(MD: −11.74 ml/min/1.73 m2; 95% CI: −13.15, −10.32; p < 0.00001)]. The postoperative complication rate of PN was higher than that of PN (OR: 2.09; 95% CI: 1.56, 2.80; p < 0.00001)], and the postoperative overall survival (OS) of PN was higher than that of RN (HR: 0.77; 95% CI: 0.65, 0.90; p = 0.002), and tumor recurrence (RR, 0.69; 95% CI: 0.53, 0.90; p = 0.007). No obvious publication bias was found in the funnel chart of the OS rates of the two groups of patients.ConclusionsPN is beneficial for patients with T2 renal tumors in terms of OS and renal function protection. However, it is also associated with a higher risk of surgical complications.

Ischemia-reperfusion injury (IRI) is a complex pathophysiological process that is often characterized as a blood circulation disorder caused due to various factors (such as traumatic shock, surgery, organ transplantation, burn, and thrombus). Severe metabolic dysregulation and tissue structure destruction are observed upon restoration of blood flow to the ischemic tissue. Theoretically, IRI can occur in various tissues and organs, including the kidney, liver, myocardium, and brain, among others. The advances made in research regarding restoring tissue perfusion in ischemic areas have been inadequate with regard to decreasing the mortality and infarct size associated with IRI. Hence, the clinical treatment of patients with severe IRI remains a thorny issue. Peroxisome proliferator-activated receptor γ (PPARγ) is a member of a superfamily of nuclear transcription factors activated by agonists and is a promising therapeutic target for ameliorating IRI. Therefore, this review focuses on the role of PPARγ in IRI. The protective effects of PPARγ, such as attenuating oxidative stress, inhibiting inflammatory responses, and antagonizing apoptosis, are described, envisaging certain therapeutic perspectives.

Although the cases of endometrial carcinoma (EC) is gradually increasing across the world, its etiology and pathogenesis remain unknown. The present study is the first to define the role and biological function of circRNA hsa_circ_0075960 in the development and progression of EC. We first determined that hsa_circ_0075960 is aberrantly expressed in EC cells. Then, we uncovered that the downregulation of hsa_circ_0075960 suppressed cell proliferation and promoted cell apoptosis of EC cells, suggesting that hsa_circ_0075960 could inhibit the progression of EC in vitro . In addition, we identified that miR-361-3p was the direct target of hsa_circ_0075960. Further analysis revealed that hsa_circ_0075960 affected the development of EC via sponging miR-361-3p. Interestingly, we verified that the level of SH2B1 was controlled by the downregulation of hsa_circ_0075960 and that the negative effect caused by hsa_circ_0075960 could be reversed via miR-361-3p inhibition. Our cumulative results revealed that the novel tumor regulator hsa_circ_0075960 functioned as a sponge for miR-361-3p/SH2B1 in EC cells and regulated the progression of EC through the modulation of miR-361-3p.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that accounts for the largest proportion of breast cancer-related deaths. Thus, it is imperative to search for novel drug candidates with potent anti-TNBC effects. Recent studies suggest that isoliquiritigenin (ISL) can significantly suppress the growth, migration, and invasion of breast cancer cells. We previously synthesized ISL derivatives and found that 3′,4′,5′,4″-tetramethoxychalcone (TMC) inhibits TNBC cell proliferation to a greater degree than ISL. The present study aimed to investigate the mechanisms underlying the anti-TNBC effects of TMC in vitro and in vivo. We show that TMC significantly inhibits the proliferative, migratory, and invasive abilities of MDA-MB-231 and BT549 cells. TMC induces apoptosis through the upregulation of Bax and downregulation of Bcl-2. PCR arrays demonstrate a significant decrease in miR-374a expression in TNBC cells after 24-h TMC treatment. MiR-374a is overexpressed in TNBC cells and has oncogenic properties. Real-time PCR analysis confirmed that TMC inhibits miR-374a in a dose-dependent manner, and luciferase assays confirmed that BAX is targeted by miR-374a. Further, we show that TMC increases Bax protein and mRNA levels by inhibiting miR-374a. TMC also attenuates TNBC tumor volumes and weights in vivo. These results demonstrate that TMC inhibits TNBC cell proliferation, foci formation, migration, invasion, and tumorigenesis, suggesting its potential to serve as a novel drug for treating TNBC through miR-374a repression.