Chemokine CC motif ligand 20 (CCL20) is a molecule with immunomodulatory properties that is involved in the regulation of diseases such as chronic inflammation, autoimmune diseases, and cancer. It operates by binding to its specific receptor, CC chemokine receptor type 6 (CCR6), and activating a complex intracellular signaling network. Building on its established role in inflammatory diseases, recent research has expanded our understanding of CCL20 to encompass its critical contributions to the tumor microenvironment (TME), highlighting its significance in cancer progression. Numerous studies have emphasized its prominent role in regulating immune responses. Consequently, Monoclonal antibodies against CCL20 and inhibitors of CCR6 have been successfully developed to block downstream signaling, making the CCL20-CCR6 axis a promising and critical target in the TME. This offers potential immunotherapeutic strategies for cancers. In this review, we summarize the biological consequences of CCL20-CCR6 mediated signaling, its role and mechanisms in the TME, and its potential applications. We suggest that the CCL20-CCR6 axis may be a novel biomarker for tumor diagnosis and prognosis, as well as a therapeutic target in various cancers.

Long non-coding RNAs (lncRNAs) are significant regulators of myoblast proliferation, migration and regeneration. In our previous research, we identified that lncRNA AK159072 was differentially expressed during myoblast development. In this study, we would like to explore the regulatory role and the mechanisms of AK159072 in proliferation. We discovered that AK159072 was increasingly expressed during myoblast proliferation and was located in both the nucleus and cytoplasm of proliferating C2C12 myoblasts. Overexpression of AK159072 promoted the expression of proliferation-related genes c-Myc, cyclin-dependent kinase 2 (CDK2), CDK4, and CDK6 in C2C12 myoblasts. Additionally, the cell viability and EdU-positive cells were increased, while the wound size was decreased after overexpression AK159072. In contrast, cell proliferation was attenuated when AK159072 was successfully silenced. Furthermore, the cross sectional area (CSA) and proliferative markers were decreased after knockdown of AK159072 in the mouse hind leg muscles with CTX-induced injury in vivo, indicating that knockdown of AK159072 may delay muscle regeneration. The study further demonstrated that Akt/Foxo1 pathway mediated the effects of AK159072 overexpression and knockdown in myoblasts. Taken together, our results suggested that AK159072 may regulate myoblast proliferation and muscle regeneration via Akt/Foxo1 pathway. The study suggestd that modulating the expression of AK159072 could be a potential therapeutic strategy for muscle injuries, this could have significant clinical relevance for conditions such as muscular dystrophy, sarcopenia, and other muscle disorders.

The immunosuppressive tumor microenvironment (TME) shaped by tumor-associated macrophages (TAMs) is essential for lung adenocarcinoma (LUAD) immune tolerance and tumor progression. Here, we first reported that proteinase 3 (PRTN3) promoted the alternative activation (M2) of TAMs and enhanced IL33/regulatory T cells (Tregs)-mediated tumor immunosuppression in LUAD. Firstly, clinical analysis revealed PRTN3 was highly expressed in TAMs and correlated with the tumor progression and poor prognosis in LUAD patients. Meanwhile, by using the myeloid cells-specific Prtn3-knockout mouse model, we demonstrated Prtn3 deficiency in macrophages remolded the immunosuppressive TME and suppressed tumor growth. The mechanism studies uncovered a novel signaling pathway that PRTN3 up-regulated IL33 expression in TAMs by suppressing AKT-mediated ubiquitinated degradation of FOXO1, which subsequently activated Il33 transcription. Furthermore, lack of PRTN3 or FOXO1 in macrophages greatly restrained IL33-induced Treg differentiation. Importantly, selective knockout of Prtn3 in macrophages significantly enhanced the antitumor effect of anti-PD1 therapy in the mouse model of LUAD. Thus, our work demonstrated that PRTN3 in macrophages, served as a key immunoregulator, contributed to impede the antitumor immune response through reinforcing the TAMs/Tregs crosstalk, which provided valuable insights to improve the immunotherapeutic effect by functional remodeling of TAMs to alleviate immunosuppression in LUAD.

In the development of several cancers, the Forkhead Box M1 (FOXM1) is crucial. The relationship between the immune system and FOXM1 in renal cell carcinoma (ccRCC), which has been verified by bulk RNA sequencing and scRNA sequencing, is the primary subject of this research.

Publicly available data related to FOXM1 and ccRCC were extracted from The Cancer Genome Atlas (TCGA) database. The impact of FOXM1 on the prognosis of ccRCC was examined using Cox regression analysis. Results were verified by immunohistochemistry and quantitative real-time PCR (qRT-PCR). Additionally, single-cell sequencing data were analyzed.

When compared to para-carcinoma tissues, the expression of FOXM1 was considerably higher in ccRCC tissues. Patients with elevated FOXM1 expression had lower survival rates. FOXM1 may be a standalone prognostic factor for ccRCC, according to results of univariate and multivariate Cox regression studies. Reduced FOXM1 expression was linked to higher immunotherapy sensitivity, according to immunocorrelation analysis. This suggests FOXM1 may mediate immunotherapy resistance in ccRCC. Additionally, FOXM1 showed strong associations with tumor mutation load, microsatellite instability, and antitumor immunity. These results imply FOXM1 may regulate antitumor immunity in the ccRCC microenvironment. Consistent results from immunohistochemistry, PCR, and single-cell RNA sequencing confirmed upregulated FOXM1 expression in ccRCC.

According to the findings, FOXM1 might be used as a stand-alone prognostic biomarker for ccRCC. Moreover, FOXM1 has exhibited robust correlations with microsatellite instability, tumor mutation burden, immune response, and immunotherapy efficacy. FOXM1 may promote ccRCC pathogenesis partly by suppressing antitumor immunity and mediating immunotherapy resistance.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder among fertile women, which is influenced by genetics and environment. A recent study revealed that PCOS patients were in a chronic inflammatory state, and they had abnormally activated macrophages. This paper introduces the relationship between PCOS and macrophages. The forkhead box protein O1 (FOXO-1), migration inhibitory factor, sympathetic conservation disorder, and vitamin D are believed to influence macrophages in PCOS. There is evidence that PCOS-associated abnormalities are associated with macrophages, including insulin resistance, obesity, hyperandrogenism (HA), hyperhomocysteinemia (HHcy), cardiometabolic disorder and gut microbiota dysbiosis. This review summarizes the research status of macrophages in PCOS. Macrophages might be a potential PCOS treatment candidate.

Studies have indicated that cyclin dependent protein kinase inhibitor 2B (CDKN2B) deletion is one of the most common changes in esophageal cancer (EC) which affects its progression and prognosis. This study explored the association between CDKN2B deletion, immunophenotype, and the prognosis of EC.

We investigated CDKN2B status and RNA expression, identified differentially expressed immune-associated genes between wild-type CDKN2B (CDKN2BWT) and deleted CDKN2B (CDKN2Bdeletion) in Cancer Genome Atlas (TCGA) EC samples. We also a constructed an immune prognostic model (IPM) based on these genes. Thereafter, the effects of IPM on the immune microenvironment of EC were analyzed. Finally, we established a nomogram by integrating the IPM and other clinical factors.

CDKN2B deletion leads to downregulation of the immune response in EC. A total of 136 immune-associated genes were identified based on the CDKN2B deletion status, and three genes with remarkable potential as individual targets were selected for model construction. An IPM was developed and validated, it showed good performance in differentiating patients with a low or high risk of poor prognosis, and its predictive ability was independent of traditional clinical features. High-risk patients with EC had increased T follicular helper cells (Tfh) and M0 macrophages, and lower infiltration levels of resting CD4 memory T cells resting, and naive B cells. The nomogram developed for clinical application showed good predictive performance.

Our results suggested that CDKN2B deletion was associated with the survival and immune microenvironment in EC. IPM is not only an effective indicator of the immune response and prognosis, but also suggest potential targets for immunotherapy in patients with EC.

Our team previously reported that MACC1 levels are closely related to a variety of tumors and the efficacy of immune checkpoint blockade (ICB) therapy. However, the predictive value of MACC1 levels for lung adenocarcinoma (LUAD) immunotherapy has not been studied. This study aimed to investigate the predictive effect of the oncogene MACC1 on ICB reactivity in patients with LUAD. First, the expression patterns and clinical features of MACC1 in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were comprehensively evaluated using R packages. We subsequently assessed the correlations between MACC1 and immunological characteristics in the LUAD tumor microenvironment (TME) using the CIBERSORT algorithm. The results revealed that MACC1 overexpression was significantly correlated with 3 immune checkpoints, 14 tumor-infiltrating immune cells (TIICs), 9 immunomodulators, 5 anticancer immune process activities, and 3 effector genes of TIICs in LUAD. Additionally, on the basis of the prognostic genes from LASSO analysis, we developed the MACC1-related Risk Score (MRRS), which can accurately predict the prognosis and response to cancer immunotherapy in LUAD patients (HR = 3.50, AUC at 1, 2, and 3 years = 0.737, 0.744, and 0.724, respectively). Finally, in vivo experiments revealed that the combination of MACC1 silencing and PD-L1 inhibitors significantly inhibits tumor progression. These findings increase our understanding of MACC1 as a potential prognostic biomarker and potential therapeutic target for cancer immunotherapy. The MRRS may play a critical role in predicting the response of LUAD patients to ICB therapy.

Focal adhesion kinase (FAK) expression has been linked to tumor growth, immunosuppression, metastasis, angiogenesis, and therapeutic resistance through kinase-dependent and kinase scaffolding functions in the nucleus and cytoplasm. Hence, targeting FAK alone or with other agents has gained attention as a potential therapeutic strategy. Moreover, mounting evidence shows that FAK activity can influence the tumor immune microenvironment crosstalk to support tumor progression. Recently, tumor immune microenvironment interaction orchestrators have shown to be promising therapeutic agents for cancer immunotherapies. Therefore, this review highlights how FAK regulates the tumor immune microenvironment interplay to promote tumor immune evasive mechanisms and their potential for combination therapies with standard cancer treatments.

Immunotherapy is recognized as an effective and promising treatment modality that offers a new approach to cancer treatment. However, identifying responsive patients remains challenging. Anoikis, a distinct form of programmed cell death, plays a crucial role in cancer progression and metastasis. Thus, we aimed to investigate prognostic biomarkers based on anoikis and their role in guiding immunotherapy decisions for esophageal squamous cell carcinoma (ESCC). By consensus clustering, the GSE53624 cohort of ESCC patients was divided into two subgroups based on prognostic anoikis-related genes (ARGs), with significant differences in survival outcomes between the two subgroups. Subsequently, we constructed an ARGs signature with four genes, and its reliability and accuracy were validated both internally and externally. Additional, different risk groups showed notable variances in terms of immunotherapy response, tumor infiltration, functional enrichment, immune function, and tumor mutation burden. Notably, the effectiveness of the signature in predicting immunotherapy response was confirmed across multiple cohorts, including GSE53624, GSE53625, TCGA-ESCC, and IMvigor210, highlighting its potential utility in predicting immunotherapy response. In conclusion, the ARGs signature has the potential to serve as an innovative and dependable prognostic biomarker for ESCC, facilitating personalized treatment strategies in this field, and may represent a valuable new tool for guiding ESCC immunotherapy decision-making.

Esophageal carcinoma (ESCA) is a highly malignant tumor with the highest incidence in Eastern Asia. Although treatment modalities for ESCA have advanced in recent years, the overall prognosis remains poor, as most patients are diagnosed at an advanced stage of the disease. There is an urgent need to promote early screening for ESCA to increase survival rates and improve patient outcomes. The development of ESCA is closely linked to the complex tumor microenvironment (TME), where chemokines and their receptors play pivotal roles. Chemokines are a class of small-molecule, secreted proteins and constitute the largest family of cytokines. They not only directly regulate tumor growth and proliferation but also influence cell migration and localization through specific receptor interactions. Consequently, chemokines and their receptors affect tumor invasion and metastatic spread. Furthermore, chemokines regulate immune cells, including macrophages and regulatory T cells, within the TME. The recruitment of these immune cells further leads to immunosuppression, creating favorable conditions for tumor growth and metastasis. This review examines the impact of ESCA-associated chemokines and their receptors on ESCA, emphasizing their critical involvement in the ESCA TME.

Acute lung injury (ALI) is a critical condition characterized by severe inflammation and oxidative stress, leading to high morbidity and mortality. Despite advances in understanding ALI pathophysiology, effective treatment options remain limited. The increasing global burden of ALI, driven by factors such as infections, trauma, and environmental pollutants, emphasizes the urgent need for new therapeutic strategies. This study investigates the role of ubiquitin-specific protease 11 (USP11) in modulating Forkhead box protein O1 (FOXO1) to promote autophagy and alleviate oxidative stress in lung epithelial cells, which could provide novel insights into ALI therapeutic strategies.

Bioinformatics were utilized to analyze the expression pattern of USP11 and FOXO1 in ALI, and their functions were detected based on gain- and loss-of function studies in vitro and in vivo. Besides, the effects of USP11 on FOXO1 stability and autophagy were examined through Western blot, immunofluorescence, and co-immunoprecipitation assays.

USP11 was found to be significantly downregulated in ALI, and its over-expression stabilized FOXO1, enhancing autophagy in lung epithelial cells. USP11 over-expression reduced oxidative stress and inflammatory cytokine production in vitro and in vivo. These results highlight the protective role of the USP11-FOXO1 axis in mitigating ALI pathophysiology.

This study identifies USP11 as a key regulator of FOXO1 and autophagy in ALI. The stabilization of FOXO1 through USP11 represents a promising therapeutic strategy for reducing oxidative stress and inflammation in ALI, warranting further clinical investigation.

Non-small cell lung cancer (NSCLC) patients are characterized by distant metastasis and poor prognosis. Growing evidence has implied that circular RNAs (circRNAs) are involved in multiple tumor progression, including NSCLC. The objective of the present study was to functionally dissect the role and mechanism of circ_BLNK in NSCLC development and progression. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expression of circ_BLNK, miR-942-5p, and forkhead box protein O1 (FOXO1) in NSCLC tissues and cells. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, 5-ethynyl-2'-deoxyuridine (EdU) assay and colony formation assay detected cell proliferation; the protein expression levels were tested by western blot assay; cell apoptosis was measured by flow cytometry, and transwell assay detected cell migration and invasion. The molecular targeting relationship was determined by dual-luciferase reporter assay. The effect of circ_BLNK overexpression on tumor growth was detected by in vivo experiments and immunohistochemistry. Circ_BLNK was dramatically decreased in NSCLC, and overexpression of circ_BLNK inhibited proliferation, migration, and invasion of NSCLC cells and promoted cell apoptosis. Circ_BLNK level was negatively correlated with miR-942-5p expression and positively correlated with FOXO1 expression. Moreover, circ_BLNK acted as a sponge for miR-942-5p, which targeted FOXO1. Rescue assays presented that miR-942-5p reversed the anticancer action of circ_BLNK in NSCLC. Besides that, miR-942-5p inhibition suppressed the oncogenic behaviors, which were attenuated by FOXO1 knockdown. Animal experiments exhibited that circ_BLNK upregulation repressed tumor growth in vivo. Our study demonstrated a novel regulatory mechanism that circ_BLNK/miR-942-5p/FOXO1 axis adjusted non-small cell lung cancer development.

Tumor-associated macrophages (TAMs) are present in and are important components of the tumor microenvironment (TME). TAMs differentiate into 2 functionally distinct morphologies, classically activated (M1)-type TAMs and alternatively activated (M2)-type TAMs, when stimulated by different cytokines. The 2 types of TAMs exhibit distinct properties and functions. M1 TAMs secrete high levels of pro-inflammatory and chemotactic factors, exerting proinflammatory, antitumor effects. Conversely, M2 TAMs alter the extracellular matrix, facilitate cellular immune escape, and stimulate tumor angiogenesis, thereby promoting anti-inflammatory responses and tumor growth. The ratio of M1 TAMs to M2 TAMs in the TME is closely related to the prognosis of the tumor. Tumor cells and other cells in the TME can regulate the polarization of TAMs and thus promote tumor progression through the secretion of various substances; however, polarized TAMs can also act on various cells in the TME through the secretion of exosomes, thus forming a positive feedback loop. Therefore, modulating the phenotype of TAMs in the TME or blocking the polarization of M2 TAMs might be a new approach for cancer treatment. However, the intracellular signaling pathways involved in the polarization of TAMs are poorly understood. The AKT signaling pathway is an important signaling pathway involved in the polarization, growth, proliferation, recruitment, and apoptosis of TAMs, as well as the action of TAMs on other cells within the TME. This paper reviews the AKT signaling pathway in the polarization of TAMs and the regulation of the TME and provides new ideas for tumor immunotherapy.

Patients suffer from esophageal squamous cell carcinoma (ESCC), which is the ninth highly aggressive malignancy. Tumor-infiltrating immune cells (TIIC) exert as major component of the tumor microenvironment (TME), showing possible prognostic value in ESCC.

Transcriptome data and scRNA-seq data of ESCC samples were extracted from the GEO and TCGA databases. Tissue Specific Index (TSI) was defined to identify potential TIIC-RNAs from the TME. Twenty machine learning algorithms were further applied to evaluate the prognostic efficacy of TIIC signature score. Gene colocalization analysis was performed. Differences in CNV on chromosomes and SNP sites of prognostic model genes were calculated.

The most reliable model of TIIC signature score was developed based on three prognostic TIIC-RNAs. It showed a higher C-index than any other reported prognostic models. ESCC patients with high TIIC signature score showed poorer survival outcomes than low TIIC signature score. The activity of most immune cells decreased with the increase of TIIC score. TIIC signature score showed difference in the expression levels and methylation levels of DEGs. There was also significant different correlation with the degree of CNV amplification and CNV deletion of the immune checkpoint genes. Gene colocalization analysis showed two prognostic model genes (ATP6V0E1 and BIRC2). MR analysis found that rs148710154 and rs75146099 SNP sites of TIIC-RNA gene had a significant correlation between them gastro-oesophageal reflux and ESCC.

TIIC signature score was the first time developed which provided a novel strategy and guidance for the prognosis and immunotherapy of ESCC. It also gave the evidence in the important role of immune cells from the TME in the treatment of cancers.

This study investigates the effects of Physcion on esophageal cancer and its possible mechanisms of action. Potential Physcion targets were identified using databases. Transcriptomic data from 17 esophageal cancer and adjacent tissues were analyzed to find differentially expressed genes, intersecting with potential targets to select 16 key genes. Their expression and distribution were evaluated in patient sequencing data. Diagnostic potential was assessed through differential gene expression and ROC curves. Pathway enrichment analysis was performed using KEGG, and molecular docking simulations were conducted to assess Physcion's binding affinity to key genes. In vitro assays complemented these findings. A total of 161 drug targets were identified, narrowing down to 16 pivotal genes. Expression patterns were examined across cell populations, and enrichment analysis showed significant PI3K/AKT pathway involvement. Molecular docking indicated strong binding of Physcion to HSP90AA1 and MMP2. In vitro assays confirmed Physcion's dose- and time-dependent impact on esophageal cancer cells, with significant DAPI staining effects. Physcion shows promise as a therapeutic agent for esophageal cancer. The study supports its potential for clinical development and future research in esophageal cancer treatment.

Endometriosis (EM) is known as a common estrogen-dependent chronic inflammatory disease. Elevated levels of Forkhead box L2 (FOXL2) have been observed in uterine diseases, including EM. However, the molecular mechanism of FOXL2 in EM needs to be further illustrated. This study aimed to investigate the regulatory role of FOXL2 in EM rats and isolated ectopic endometrial stromal cells (EC-ESCs).

FOXL2 knockdown were designed to evaluate the effects of FOXL2 in EM model rats and EC-ESCs. Hematoxylin-eosin (HE) staining was used to evaluate the pathological morphology of ectopic endometrium. Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) analysis and immunohistochemistry (IHC) were applied to detect the expression of FOXL2, EM-related genes, and epithelial to mesenchymal transition-related proteins. The proliferation, migration, invasion, and apoptosis of EC-ESCs were determined by 5-ethynyl-2'-deoxyuridine (EDU) assay, Transwell assay, and flow cytometry.

The FOXL2 level was remarkably higher in the ectopic endometrial tissue than that in the normal endometrial tissue. Knockdown of FOXL2 notably improved the pathological morphology of EM in rats, and decreased expression levels of ER-α, ER-ß, and Cyp19a. Additionally, down-regulation of FOXL2 suppressed cells proliferation, migration and invasion, and stimulated more apoptotic cells in EC-ESCs. Besides, FOXL2-small interfering RNA (FOXL2-siRNA) treatment resulted in enhanced cleaved-Caspase3 protein expression and cleaved-Caspase3/Caspase3 ratio in EC-ESCs.

FOXL2 participates in the occurrence and development of EM through promoting epithelial-mesenchymal transition procession and enhancing the migration and invasion of EC-ESCs, suggesting that FOXL2 may be a new therapeutic target for the EM therapy.

Esophageal squamous cell carcinoma (ESCC) is a lethal malignancy, and the molecular underpinnings of its aggressive behavior are not fully understood. FYN proto-oncogene, Src family tyrosine kinase (FYN) has been linked to cancer progression, yet its role in ESCC remains elusive. This study investigated the influence of FYN on ESCC malignancy.

Quantitative real-time polymerase chain reaction was used to assess the mRNA expression of FYN, while western blotting and immunohistochemistry (IHC) assays were performed to detect the protein expression of FYN, ubiquitin specific peptidase 8 (USP8) and protein tyrosine kinase 2 (PTK2). Cell viability was measured with a cell counting kit-8 assay, and cell apoptosis was evaluated using flow cytometry.

FYN expression was increased in ESCC tissues and cells when compared with normal esophageal tissues and normal esophageal epithelial cells. Knockdown of FYN inhibited cell invasion, migration, stem-like traits, and glycolysis, while promoting apoptosis. USP8 was shown to stabilize FYN protein expression through its deubiquitinating activity in ESCC cells. Overexpression of FYN reversed the effects of USP8 silencing on the malignant phenotypes of ESCC cells in vitro and in vivo. FYN upregulated PTK2 expression in both TE1 and KYSE150 cell lines. Furthermore, PTK2 overexpression reversed the effects of FYN silencing on the malignant phenotypes of ESCC cells. Further, USP8 silencing-induced inhibitory effect on PTK2 protein expression was counteracted after FYN overexpression.

USP8-dependent FYN contributed to the malignant progression of ESCC by interacting with PTK2. Targeting this pathway may offer a novel therapeutic strategy for ESCC treatment.

Esophageal squamous cell carcinoma (ESCC) is one of the deadliest cancers because of its high invasiveness and low survival. Tumor-associated macrophages (TAMs) are closely associated with the tumor cell proliferation, metastasis and immunosuppression. As a member of the FOX family, forkhead box F2 (FOXF2) was down-regulated in ESCC. However, its role in ESCC and TAMs, as well as the underlying mechanism, remains unclear. We found that differentially expressed genes (DEGs) in ESCC were enriched in proliferation, migration, macrophage and cancer pathways. Among these DEGs, FOXF2 caught our eyes. FOXF2 was down-regulated in ESCC. Overexpression FOXF2 inhibited the proliferation of ESCC cells and the M2 polarization of TAMs, but silenced FOXF2 reversed these results. Notably, FOXF2 promoted the transcription of ring finger protein 144A (RNF144A), which is an E3 ubiquitin ligase, causing the ubiquitination and degradation of FTO Alpha-Ketoglutarate Dependent Dioxygenase (FTO), an N6-methyladenosine (m6A) demethylase. Furthermore, overexpression of FTO abolished the effects of FOXF2 on TAM polarization. In conclusion, FOXF2 alleviates ESCC via promoting the transcription of RNF144A which results in the ubiquitylation and degradation of FTO. Targeting FOXF2/RNF144A/FOT axis might be a possible strategy for the treatment of ESCC.

Introduction: Photodynamic therapy (PDT) is a photochemical treatment that involves the use of light and photosensitizer. This method is applied as a therapeutic approach against several types of cancer. The main aim of this study is to compare the efficacy of PDT with that of cisplatin (a well-known chemotherapy agent) through protein-protein interaction (PPI) network analysis. Methods: Gene expression profiles of human melanoma A375 cells from the Gene Expression Omnibus (GEO) were selected for analysis via directed PPI network analysis. The significant differentially expressed genes (DEGs) were identified and assessed based on co-expression interactions. The critical DEGs were introduced by considering out-degree and in-degree values. Results: Two directed PPI networks for upregulated and downregulated DEGs were constructed. TP53 was identified as a critical upregulated gene in response to cisplatin in comparison with PDT. EGFR, PPARG, MMP9, PTGS2, FOXO1, and RUNX2 were highlighted as the crucial downregulated genes due to the effect of cisplatin on the gene expression of the treated cells. Conclusion: Cisplatin directly targets key cellular functions such as cell growth, differentiation, migration, and invasion. It seems that the combination of cisplatin and PDT is a suitable method for treating cancers because cisplatin targets the key genes responsible for cancer development, while PDT intensifies the effect of cisplatin and reduces its side effects.

Ovarian cancer (OC) is often associated with an unfavorable prognosis. Given the crucial involvement of lysosomes in tumor advancement, lysosome-related genes (LRGs) hold promise as potential therapeutic targets.

To identify differentially expressed lysosome-related genes (DE-LRGs), we performed a matching analysis between differentially expressed genes (DEGs) in OC and the pool of LRGs. Genes with prognostic significance were analyzed using multiple regression analyses to construct a prognostic risk signature. The model's efficacy was validated through survival analysis in various cohorts. We further explored the model's correlation with clinical attributes, tumor microenvironment (TME), mutational patterns, and drug sensitivity. The quantitative real-time polymerase chain reaction (qRT-PCR) validated gene expression in OC cells.

A 10-gene prognostic risk signature was established. Survival analysis confirmed its predictive accuracy across cohorts. The signature served as an independent prognostic element for OC. The high-risk and low-risk groups demonstrated notable disparities in terms of immune infiltration patterns, mutational characteristics, and sensitivity to therapeutic agents. The qRT-PCR results corroborated and validated the findings obtained from the bioinformatic analyses.

We devised a 10-LRG prognostic model linked to TME, offering insights for tailored OC treatments.

Understanding the stepwise progression of esophageal squamous cell carcinoma (ESCC) is crucial for developing customized strategies for early detection and optimal clinical management. Herein, we aimed to unravel the transcriptional and immunologic alterations occurring during malignant transformation and identify clinically significant biomarkers of ESCC.

Digital spatial profiling (DSP) was performed on 11 patients with early-stage ESCC (pT1) to explore the transcriptional alterations in epithelial, immune cell, and non-immune cell stromal compartments across regions of distinct histology, including normal tissues, low- and high-grade dysplasia, and cancerous tissues. Furthermore, single-cell spatial transcriptomics was performed using the CosMx Spatial Molecular Imaging (SMI) system on 4 additional patients with pT1 ESCC. Immunohistochemical (IHC) analysis was performed on consecutive histological sections of 20 pT1 ESCCs. Additionally, public bulk and single-cell RNA-sequencing (scRNA-seq) datasets were analyzed, and in vitro and in vivo functional studies were conducted.

Spatial transcriptional reprogramming and dynamic cell signaling pathways that determined ESCC progression were delineated. Increased infiltration of macrophages from normal tissues through dysplasia to cancerous tissues occurred. Macrophage subtypes were characterized using the scRNA-seq dataset. Cell-cell communication analysis of scRNA-seq and SMI data indicated that the migration inhibitory factor (MIF)-CD74 axis may exhibit pro-tumor interactions between macrophages and epithelial cells. DSP, SMI, and IHC data demonstrated that DTX3L expression in epithelial cells and BST2 expression in stromal cells increased gradually with ESCC progression. Functional studies demonstrated that DTX3L or BST2 knockdown inhibited ESCC proliferation and migration and decreased M2 polarization of tumor-associated macrophages.

Spatial profiling comprehensively characterized the molecular and immunological hallmarks from normal tissue to ESCC, guiding the way to a deeper understanding of the tumorigenesis and progression of this disease and contributing to the prevention of ESCC. Within this exploration, we uncovered biomarkers that exhibit a robust correlation with ESCC progression, offering potential new avenues for insightful therapeutic approaches.

Four newly identified benzophenone analogs [nigrophenone A-D (1-4)] and a pyrrolidinone analog [nigropyrrolidinone (5)], alongside thirteen known congeners (6-18), were isolated from Nigrospora sphaerica. Transcriptome analysis revealed that 6 might have the potential to modulate T-cell immunity. Quantitative measurements of the binding affinities between eighteen natural molecules and the immunological checkpoint receptors PD-1 and PD-L1 were performed using Surface Plasmon Resonance (SPR). The results of SPR analysis showed that 1-18 have KD values ranging from 1.8 to 99.5 μM for PD-1 and from 10.6 to 99.5 μM for PD-L1. Competitive inhibition studies, employing SPR and ELISA assays, have indicated that compounds 6, 10, 15, and 18 are capable of inhibiting the PD-1/PD-L1 interaction. Additionally, compound 6 exhibited notable in vitro anticancer potency through the augmentation of activating signals and the upregulation of PD-1 expression on CD8+ T cells, concurrently elevating the secretion of IFN-γ and IL-2, thereby inhibiting the proliferation of LLC and MC38 cells and promoting MC38 apoptosis. Moreover, compound 6 modulates the PI3K/Akt pathway, which is a key downstream effector of the PD-1/PD-L1 axis. These compounds are considered promising candidates for more in-depth exploration because they could significantly inhibit PD-1/PD-L1 interactions in tumor immunotherapy.

In the realm of cancer research, the tumor microenvironment (TME) plays a crucial role in tumor initiation and progression, shaped by complex interactions between cancer cells and surrounding non-cancerous cells. Cytokines, as essential immunomodulatory agents, are secreted by various cellular constituents within the TME, including immune cells, cancer-associated fibroblasts, and cancer cells themselves. These cytokines facilitate intricate communication networks that significantly influence tumor initiation, progression, metastasis, and immune suppression. Pyroptosis contributes to TME remodeling by promoting the release of pro-inflammatory cytokines and sustaining chronic inflammation, impacting processes such as immune escape and angiogenesis. However, challenges remain due to the complex interplay among cytokines, pyroptosis, and the TME, along with the dual effects of pyroptosis on cancer progression and therapy-related complications like cytokine release syndrome. Unraveling these complexities could facilitate strategies that balance inflammatory responses while minimizing tissue damage during therapy. This review delves into the complex crosstalk between cytokines, pyroptosis, and the TME, elucidating their contribution to tumor progression and metastasis. By synthesizing emerging therapeutic targets and innovative technologies concerning TME, this review aims to provide novel insights that could enhance treatment outcomes for cancer patients.

Tumor-associated macrophages (TAMs) play a crucial role in shaping various tumor microenvironments. However, their recruitment in Wilms tumor (WT), the predominant malignant renal tumor in children, has been inadequately explored. This retrospective cohort study involved the analysis of 148 WT samples to investigate the recruitment and polarization typing of TAMs in WT tissues.

WT tissues underwent Western blotting (WB), reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and immunofluorescence (IF) to measure the expression of TAM markers CD68, CD86, and CD163. Statistically analyze the relationship between TAM recruitment levels and patient clinical characteristics, and use Kaplan-Meier curves and the log-rank test to evaluate the association between TAM levels and survival outcomes.

The findings indicated a positive correlation between the recruitment levels of total macrophages (Mtotal) and M2 tumor-associated macrophages (M2 TAM) in both chemotherapy and non-chemotherapy groups with the clinical stage. Elevated recruitment of Mtotal and M2 TAM in tumor tissues was linked to a poorer prognosis. Notably, patients with persistently higher recruitment of M2 TAM following preoperative chemotherapy exhibited the worst prognosis.

The recruitment and polarization typing of TAM exhibit significant differences in WT patients with various stages and prognosis outcomes, suggesting a potential avenue for future diagnosis and treatment of WT.

Prostate cancer (PC), a malignant tumor occurring in the male prostate tissue, has a high incidence rate. In this study, we explored the role of tripartite motif 47 (TRIM47) in the progression of PC and its underlying mechanism.

PC and paracancerous tissues were collected from Shenzhen Peoples's Hospital. The following methods were employed in this experiment: quantitative polymerase chain reaction (qPCR), immunofluorescent staining, cell counting kit-8 (CCK-8), ethynyl deoxyuridine (EdU), and Western blot.

The expression levels of TRIM47 were up-regulated in patients with PC. TRIM47 was found to promote cell growth and induce the Warburg effect, while also reducing ferroptosis in PC cells. Conversely, the knockdown of TRIM47 [small interfering RNA, (si)-TRIM47] decreased cell growth and the Warburg effect, while promoting ferroptosis in PC cells. Additionally, TRIM47 was observed to induce the protein expression levels of fructose-1,6-bisphosphatase 1 (FBP1) and forkhead box protein O1 (FOXO1) in PC cells. Further, TRIM47 protein was found to interact with both the FBP1 and FOXO1 proteins in the PC cells. The inhibition of FBP1 attenuated the effects of TRIM47 on the Warburg effect in PC cells, while the inhibition of FOXO1 diminished the effects of TRIM47 on ferroptosis in PC cells.

Our findings suggest that TRIM47 promotes the Warburg effect of PC by inducing FBP1 and FOXO1. Thus, our findings suggest that targeting TRIM47 could serve as a viable therapeutic strategy for the treatment of PC.

Malignant renal rhabdoid tumor (MRTK) is an aggressive and rare malignancy primarily affecting infants and young children. The intricate interactions within the Tumor Microenvironment (TME) are crucial in shaping MRTK's progression. This study elucidates the significance of tumor-associated macrophages(TAMs) within this milieu and their interplay with eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) in tumor cells, collectively contributing to MRTK's malignant advancement. Through comprehensive analysis of clinical samples and the TARGET database, EIF4EBP1 emerges as a central macrophage-associated gene with robust prognostic implications. Elevated EIF4EBP1 expression correlates with poor prognosis and heightened infiltration of TAMs. Functional validation demonstrates that EIF4EBP1 knockdown in G401 cells significantly attenuates self-proliferation, migration, and invasion. Moreover, EIF4EBP1 regulates macrophage recruitment and M2 polarization through the ERK/P38 MAPK-MIF axis. Notably, M2 macrophages reciprocally foster the malignant behavior of MRTK tumor cells. This study unveils the pivotal role of EIF4EBP1 in propelling MRTK's malignant progression, unraveling a complex regulatory network involving EIF4EBP1 and TAMs. These findings underscore EIF4EBP1 as a promising biomarker and highlight its therapeutic potential in MRTK management.

The incomplete prediction of prognosis in esophageal squamous cell carcinoma (ESCC) patients is attributed to various therapeutic interventions and complex prognostic factors. Consequently, there is a pressing demand for enhanced predictive biomarkers that can facilitate clinical management and treatment decisions. This study recruited 491 ESCC patients who underwent surgical treatment at Huashan Hospital, Fudan University. We incorporated 14 blood metabolic indicators and identified independent prognostic indicators for overall survival through univariate and multivariate analyses. Subsequently, a metabolism score formula was established based on the biochemical markers. We constructed a nomogram and machine learning models utilizing the metabolism score and clinically significant prognostic features, followed by an evaluation of their predictive accuracy and performance. We identified alkaline phosphatase, free fatty acids, homocysteine, lactate dehydrogenase, and triglycerides as independent prognostic indicators for ESCC. Subsequently, based on these five indicators, we established a metabolism score that serves as an independent prognostic factor in ESCC patients. By utilizing this metabolism score in conjunction with clinical features, a nomogram can precisely predict the prognosis of ESCC patients, achieving an area under the curve (AUC) of 0.89. The random forest (RF) model showed superior predictive ability (AUC = 0.90, accuracy = 86%, Matthews correlation coefficient = 0.55). Finally, we used an RF model with optimal performance to establish an online predictive tool. The metabolism score developed in this study serves as an independent prognostic indicator for ESCC patients.

Tumor-associated macrophages (TAMs) constitute the largest number of immune cells in the tumor microenvironment (TME). They play an essential role in promoting tumor progression and metastasis, which makes them a potential therapeutic target for cancer treatment. TAMs are usually divided into two categories: pro-tumoral M2-like TAMs and antitumoral M1 phenotypes at either extreme. The reprogramming of M2-like TAMs toward a tumoricidal M1 phenotype is of particular interest for the restoration of antitumor immunity in cancer immunotherapy. Notably, nanomedicines have shown great potential for cancer therapy due to their unique structures and properties. This review will briefly describe the biological features and roles of TAMs in tumor, and then discuss recent advances in nanomedicine-mediated repolarization of TAMs for cancer immunotherapy. Finally, perspectives on nanomedicine-mediated repolarization of TAMs for effective cancer immunotherapy are also presented.

This paper aims to investigate the current situation of cancer related fibroblasts promoting malignant development of cancer through FOXO1 protein/LIF signal, and explore the strategy of cancer treatment. Recent studies have shown that the expression of the protein forkhead box O1 (FOXO1) is increased in CAFsCAFs (Cancer-associated fibroblasts). This led researchers to investigate whether FOXO1 is involved in the role of CAFs in lung cancer. The results of the study revealed that FOXO1 is indeed upregulated in CAFs, and it positively regulates the transcription of another protein called LIF. Notably, LIF is also upregulated in both CAFs and lung cancer cells. These changes in protein expression were associated with the overexpression of FOXO1 in CAFs. Conversely, silencing FOXO1 in CAFs suppressed their effects on cancer cells and transplanted tumors. The study revealed that the downregulation of LIFR in cancer cells abolished the impact of CAFs overexpressing FOXO1 on cancer cell behavior. This suggests that the FOXO1/LIF signaling pathway is involved in mediating the malignant development of lung cancer induced by CAFs.

Triple-negative breast cancer (TNBC) still one of the most challenging sub-type in breast cancer clinical. Caffeic acid (CA) derived from effective components of traditional Chinese herbal medicine has been show potential against TNBCs. Our research has found that CA can inhibit the proliferation of TNBC cells while also suppressing the size of cancer stem cell spheres. Additionally, it reduces reactive oxygen species (ROS) levels and disruption of mitochondrial membrane potential. Simultaneously, CA influences the stemness of TNBC cells by reducing the expression of the stem cell marker protein CD44. Furthermore, we have observed that CA can modulate the FOXO1/FIS signaling pathway, disrupting mitochondrial function, inducing mitochondrial autophagy, and exerting anti-tumor activity. Additionally, changes in the immune microenvironment were detected using a mass cytometer, we found that CA can induce M1 polarization of macrophages, enhancing anti-tumor immune responses to exert anti-tumor activity. In summary, CA can be considered as a lead compound for further research in targeting TNBC.

The incidence of breast cancer (BC) continues to rise steadily, posing a significant burden on the public health systems of various countries worldwide. As a member of the tumor microenvironment (TME), CD8+ T cells inhibit cancer progression through their protective role. This study aims to investigate the role of CD8+ T cell-related genes (CTRGs) in breast cancer patients.

We assessed the abundance of CD8+ T cells in the TCGA and METABRIC datasets and obtained CTRGs through WGCNA. Subsequently, a prognostic signature (CTR score) was constructed from CTRGs screened by seven machine learning algorithms, and the relationship between the CTR score and TME, immunotherapy, and drug sensitivity was analyzed. Additionally, CTRGs' expression in different cells within TME was identified through single-cell analysis and spatial transcriptomics. Finally, the expression of CTRGs in clinical tissues was verified via RT-PCR.

The CD8+ T cell-related prognostic signature consists of two CTRGs. In the TCGA and METABRIC datasets, the CTR score appeared to be negatively linked to the abundance of CD8+ T cells, and BC patients with higher risk score show a worse prognosis. The low CTR score group exhibits higher immune infiltration levels, closely associated with inhibiting the tumor microenvironment. Compared with the high CTR score group, the low CTR score group shows better responses to chemotherapy and immune checkpoint therapy. Single-cell analysis and spatial transcriptomics reveal the heterogeneity of two CTRGs in different cells. Compared with the adjacent tissues, CD163L1 and KLRB1 mRNA are downregulated in tumor tissues.

This study establishes a robust CD8+ T cell-related prognostic signature, providing new insights for predicting the clinical outcomes and treatment responses of breast cancer patients.

Non-small cell lung cancer (NSCLC) leads as a primary cause of cancer-related premature mortality in Western populations. This study leverages cutting-edge gene-expression-profiling technologies to perform an in-depth molecular characterization of NSCLC specimens, with the objective of uncovering tumor-specific genomic alterations. By employing DNA microarray analysis, our research aims to refine the classification of NSCLC for early detection, guide molecular-targeted treatment approaches, enhance prognostication, and broaden the scientific understanding of the disease's biology. We identified widespread genomic abnormalities in our samples, including the recurrent loss of chromosomal regions 3p, 5q, 13q, and 21q and the gain of 12p. Furthermore, utilizing Metascape for bioinformatic analysis revealed critical biological pathways disrupted in NSCLC, offering promising leads for novel therapeutic interventions.

The role of long noncoding RNA (lncRNA) in tumors, particularly in gastrointestinal tumors, has gained significant attention. Accumulating evidence underscores the interaction between various lncRNAs and diverse molecular pathways involved in cancer progression. One such pivotal pathway is the PI3K/AKT pathway, which serves as a crucial intracellular mechanism maintaining the balance among various cellular physiological processes for normal cell growth and survival. Frequent dysregulation of the PI3K/AKT pathway in cancer, along with aberrant activation, plays a critical role in driving tumorigenesis. LncRNAs modulate the PI3K/AKT signaling pathway through diverse mechanisms, primarily by acting as competing endogenous RNA to regulate miRNA expression and associated genes. This interaction significantly influences fundamental biological behaviors such as cell proliferation, metastasis, and drug resistance. Abnormal expression of numerous lncRNAs in gastrointestinal tumors often correlates with clinical outcomes and pathological features in patients with cancer. Additionally, these lncRNAs influence the sensitivity of tumor cells to chemotherapy in multiple types of gastrointestinal tumors through the abnormal activation of the PI3K/AKT pathway. These findings provide valuable insights into the mechanisms underlying gastrointestinal tumors and potential therapeutic targets. However, gastrointestinal tumors remain a significant global health concern, with increasing incidence and mortality rates of gastrointestinal tumors over recent decades. This review provides a comprehensive summary of the latest research on the interactions of lncRNA and the PI3K/AKT pathway in gastrointestinal tumor development. Additionally, it focuses on the functions of lncRNAs and the PI3K/AKT pathway in carcinogenesis, exploring expression profiles, clinicopathological characteristics, interaction mechanisms with the PI3K/AKT pathway, and potential clinical applications.

Esophageal squamous cell carcinoma (ESCC) is an aggressive disease with a poor prognosis, caused by the inactivation of critical cell growth regulators that lead to uncontrolled proliferation and increased malignancy. Although Serine/Threonine Kinase 3 (STK3), also known as Mammalian STE20-like protein kinase 2 (MST2), is a highly conserved kinase of the Hippo pathway, plays a critical role in immunomodulation, organ development, cellular differentiation, and cancer suppression, its phenotype and function in ESCC require further investigation. In this study, we report for the first time on the role of STK3 kinase and its activation condition in ESCC, as well as the mechanism and mediators of kinase activation.

In this study, we investigated the expression and clinical significance of STK3 in ESCC. We first used bioinformatics databases and immunohistochemistry to analyze STK3 expression in the ESCC patient cohort and conducted survival analysis. In vivo, we conducted a tumorigenicity assay using nude mouse models to demonstrate the phenotypes of STK3 kinase. In vitro, we conducted Western blot analysis, qPCR analysis, CO-IP, and immunofluorescence (IF) staining analysis to detect molecule expression, interaction, and distribution. We measured proliferation, migration, and apoptosis abilities in ESCC cells in the experimental groups using CCK-8 and transwell assays, flow cytometry, and EdU staining. We used RNA-seq to identify genes that were differentially expressed in ESCC cells with silenced STK3 or FOXO1. We demonstrated the regulatory relationship of the TP53INP1/P21 gene medicated by the STK3-FOXO1 axis using Western blotting and ChIP in vitro.

We demonstrate high STK3 expression in ESCC tissue and cell lines compared to esophageal epithelium. Cellular ROS induces STK3 autophosphorylation in ESCC cells, resulting in upregulated p-STK3/4. STK3 activation inhibits ESCC cell proliferation and migration by triggering apoptosis and suppressing the cell cycle. STK3 kinase activation phosphorylates FOXO1Ser212, promoting nuclear translocation, enhancing transcriptional activity, and upregulating TP53INP1 and P21. We also investigated TP53INP1 and P21's phenotypic effects in ESCC, finding that their knockdown significantly increases tumor proliferation, highlighting their crucial role in ESCC tumorigenesis.

STK3 kinase has a high expression level in ESCC and can be activated by cellular ROS, inhibiting cell proliferation and migration. Additionally, STK3 activation-mediated FOXO1 regulates ESCC cell apoptosis and cell cycle arrest by targeting TP53INP1/P21. Our research underscores the anti-tumor function of STK3 in ESCC and elucidates the mechanism underlying its anti-tumor effect on ESCC.

Current therapeutic strategies for esophageal cancer (EC) patients have yielded limited improvements in survival rates. Recent research has highlighted the influence of drug metabolism enzymes on both drug response and EC development. Our study aims to identify specific drug metabolism enzymes regulated by histone acetylation and to elucidate its molecular and clinical features. CYP4F12 exhibited a notable upregulation subsequent to trichostatin A treatment as evidenced by RNA sequencing analysis conducted on the KYSE-150 cell line. The change in gene expression was associated with increased acetylation level of histone 3 K18 and K27 in the promoter. The regulation was dependent on p300. In silicon analysis of both The Cancer Genome Atlas esophageal carcinoma and GSE53624 dataset suggested a critical role of CYP4F12 in EC development, because CYP4F12 was downregulated in tumor tissues and predicted better disease-free survival. Gene ontology analysis has uncovered a robust correlation between CYP4F12 and processes related to cell migration, as well as its involvement in cytosine-mediated immune activities. Further investigation into the relationship between immune cells and CYP4F12 expression has indicated an increased level of B cell infiltration in samples with high CYP4F12 expression. CYP4F12 was also negatively correlated with the expression of inhibitory checkpoints. An accurate predictive nomogram model was established combining with clinical factors and CYP4F12 expression. In conclusion, CYP4F12 was crucial in EC development, and targeting CYP4F12 may improve the therapeutic efficacy of current treatment in EC patients. SIGNIFICANCE STATEMENT: CYP4F12 expression was downregulated in esophageal cancer (EC) patients and could be induced by trichostatin A. During EC development, CYP4F12 was linked to reduced cell migration and increased infiltration of B cells. CYP4F12 also is a biomarker as prognostic predictors and therapeutic guide in EC patients.

PD-1/PD-L1 inhibitors have become a promising therapy. However, the response rate is lower than 30% in patients with cervical cancer (CC), which is related to immunosuppressive components in tumor microenvironment (TME). Tumor-associated macrophages (TAMs), as one of the most important immune cells, are involved in the formation of tumor suppressive microenvironment. Therefore, it will provide a theoretical basis for curative effect improvement about the regulatory mechanism of TAMs on PD-L1 expression.

The clinical data and pathological tissues of CC patients were collected, and the expressions of PD-L1, CD68 and CD163 were detected by immunohistochemistry. Bioinformatics was used to analyze the macrophage subtypes involved in PD-L1 regulation. A co-culture model was established to observe the effects of TAMs on the morphology, migration and invasion function of CC cells, and the regulatory mechanism of TAMs on PD-L1.

PD-L1 expression on tumor cells could predict the poor prognosis of patients. And there was a strong correlation between PD-L1 expression with CD163+TAMs infiltration. Similarly, PD-L1 expression was associated with M1/M2-type TAMs infiltration in bioinformatics analysis. The results of cell co-culture showed that M1/M2-type TAMs could upregulate PD-L1 expression, especially M2-type TAMs may elevate the PD-L1 expression via PI3K/AKT pathway. Meanwhile, M1/M2-type TAMs can affect the morphological changes, and enhance migration and invasion abilities of CC cells.

PD-L1 expression in tumor cells can be used as a prognostic factor and is closely related to CD163+TAMs infiltration. In addition, M2-type TAMs can upregulate PD-L1 expression in CC cells through PI3K/AKT pathway, enhance the migration and invasion capabilities, and affect the tumor progression.