Biological Behavior Of Tumor Research Articles

Dynamic contrast enhanced MRI in nodal lymphoma: correlation of quantitative MR perfusion parameters with lymphoma subtype, Lugano stage and Ki-67 index.

Research into the intratumoral microenvironment in lymphoma has been escalated along with improved survival and new targeted therapies with an intent to refine risk stratification and prognostication. Various studies have reported significance of quantitative DCE-MRI parameters for predicting biological behaviour of various tumors. This study is an endeavour to supplement the existing literature on quantitative DCE-MRI in nodal lymphoma. To study the correlation of quantitative DCE-MRI parameters of Ktrans, Kep and Ve with subtype, Lugano stage at diagnosis and Ki-67 proliferation index (PI) in nodal lymphoma. 33 patients of age > 12 years with newly diagnosed nodal lymphoma underwent DCE-MRI. Ktrans, Kep and Ve were generated from extended Tofts model and correlated with lymphoma subtype, Lugano staging and Ki-67 PI. Mean Ktrans and Kep values were significantly higher in non-Hodgkin's lymphoma (NHL) than in Hodgkin's lymphoma (HL). Considering Ki-67 PI value of > 45% as aggressive lymphoma, the mean Ktrans (659.37 x 10-3min-1 versus 288.00 x 10-3min-1, p < 0.001) and Kep (1256.63 x 10-3min-1 versus 689.82 x 10-3min-1, p = 0.004) values in aggressive lymphomas were significantly higher compared to non-aggressive lymphomas. ROC curve analysis revealed a threshold Ktrans value of ≥ 359 x 10-3min-1 and Kep value of ≥ 853 x10-3 min-1 for diagnosing aggressive lymphomas with a sensitivity of 95%, 90%, specificity of 100%,82% and diagnostic accuracy of 91.7%,86.7% respectively. There was no significant difference in DCE-MRI parameters of various Lugano stage subgroups. DCE-MRI parameters have the potential to non-invasively predict the subtype, aggression and Ki-67 PI in nodal lymphoma. The knowledge that Ktrans is higher in aggressive lymphomas is novel. It adds to previous literature regarding MR perfusion in various neoplasms.

Gene mutation, clinical characteristics and pathology in resectable lung adenocarcinoma

ObjectiveWith the wide use of CT scan in clinical practice, more lung cancer was diagnosed in resectable stage. Pathological examination and genetic testing have become a routine procedure for lung adenocarcinoma following radical resection. This study analyzed special pathological components and gene mutations to explore their relationship with clinical characteristics and overall survival.MethodsClinical, pathological, and gene mutation data from 1,118 patients were collected. All patients underwent surgery at the Department of Thoracic Surgery, the Second Xiangya Hospital of Central South University. Patients were grouped based on pathological components and gene mutations. Differences in clinical features and overall survival were analyzed as well.ResultsPatients with mucinous, neuroendocrine, and poor-differentiated components were presented with more prognostic risk factors, including pleural invasion, carcinothrombosis, STAS, and advanced stages, along with varying frequencies of gene mutations. These factors significantly shortened overall survival. ALK and KRAS mutations were also associated with risk factors such as solid nodules, pleural invasion, STAS, and later stages. However, a significant reduction in overall survival was observed only in patients with the KRAS mutation. Relationship between gene mutations and pathological components still requires further investigation.ConclusionSpecial pathological components (mucinous, neuroendocrine, and poor-differentiated) and gene mutations had an influence on biological behavior of tumors, resulting in different clinical characteristics and prognosis.

Keratin Positive Giant Cell Rich Tumor of the Pelvic Bone with a HMGA2::NCOR2 Fusion: A Case Report.

Keratin positive giant cell rich tumor is a rare mesenchymal tumor first described in 2025. It can occur in both soft tissue and bone and predominantly affects young women. The tumor's biological behavior remains uncertain despite its low-grade classification. Characterized by keratin expression and a HMGA2::NCOR2 gene fusion, keratin positive giant cell rich tumors resemble conventional giant cell tumors but lacks H3-3A gene mutations. This article presents a 31-year-old woman with a keratin positive giant cell rich tumor in the pelvic bone, detailing her clinical presentation, diagnostic process, treatment, and postoperative recovery. Histological examination revealed numerous osteoclast-like giant cells within a mononuclear stroma, with RNA sequencing confirming the HMGA2::NCOR2 fusion. The patient's management included surgical resection, with no recurrence at six months follow-up. The discussion emphasizes the need for further research to understand keratin positive giant cell rich tumors pathogenesis and explore potential targeted therapies.

Bisphenol A exacerbates colorectal cancer progression through enhancing ceramide synthesis.

Bisphenol A (BPA) is a typical environmental endocrine disruptor which have been broadly confirmed to be associated with malignant tumors, including colorectal cancer (CRC). Lipid metabolism reprogramming performed important biological effects in cancer progression. While the role of lipid metabolism in CRC progression upon BPA exposure remain elusive. Here, we found that BPA exposure enhanced de novo ceramide synthesis in vitro, along with upregulated ceramide synthase in high-BPA tumor tissue of CRC patients. Simultaneously, we demonstrated that BPA exposure exacerbated tumor biological behavior and epithelial mesenchymal transition (EMT), concurrent with elevated EMT expression of CRC tissue in high BPA group. Subsequently, the inhibition of ceramide synthase and pharmacological stimulation experiments revealed that ceramide accumulation activated EMT and exacerbated CRC progression, including Cer (d18:1/16:0) and Cer (d18:1/24:1). Collectively our findings elucidated the pathogenesis of ceramide accumulation escalating tumor progression under environmental BPA exposure, providing a strong basis for further investigation of dysregulated ceramide metabolism to boost tumor development and avoid metastatic relapse.

Platelet stimulation-regulated expression of ILK and ITGB3 contributes to intrahepatic cholangiocarcinoma progression through FAK/PI3K/AKT pathway activation

ObjectiveIntrahepatic cholangiocarcinoma (iCCA) is a highly lethal hepatobiliary malignancy with an increasing incidence annually. Extensive research has elucidated the existence of a reciprocal interaction between platelets and cancer cells, which promotes tumor proliferation and metastasis. This study aims to investigate the function and mechanism underlying iCCA progression driven by the interplay between platelets and tumor cells, aiming to provide novel therapeutic strategies for iCCA.MethodsThe associations between platelets and cancer development were investigated by analyzing the peripheral blood platelet count, degree of platelet activation and infiltration in the microenvironment of patients with iCCA. By co-culturing tumor cells with platelets, the influence of platelet stimulation on the epithelial-mesenchymal transition (EMT), proliferation, and metastasis of iCCA cells was assessed through in vitro and in vivo experiments. Quantitative proteomic profiling was conducted to identify key downstream targets that were altered in tumor cells following platelet stimulation. The RNA interference technique was utilized to investigate the impacts of gene silencing on the malignant biological behaviors of tumor cells.ResultsCompared with healthy adults, patients with iCCA presented significantly higher levels of peripheral blood platelet counts, platelet activation and infiltration degrees, which were also found to be correlated with patient prognosis. Platelet stimulation greatly facilitated the EMT of iCCA cells, leading to enhanced proliferative and metastatic capabilities. Mechanistically, proteomic profiling identified a total of 67 up-regulated and 40 down-regulated proteins in iCCA cells co-cultured with platelets. Among these proteins, two elevated targets ILK and ITGB3, were further demonstrated to be partially responsible for platelet-induced iCCA progression, which might depend on their regulatory effects on FAK/PI3K/AKT signaling transduction.ConclusionsOur data revealed that platelet-related indices were abnormally ascendant in iCCA patients compared to healthy adults. Co-culturing with platelets enhanced the progression of EMT, and the motility and viability of iCCA cells in vitro and in vivo. Proteomic profiling discovered that platelets promoted the development of iCCA through FAK/PI3K/AKT pathway by means of elevating the expression of ILK and ITGB3, indicating that both proteins are promising therapeutic targets for iCCA with the guidance of platelet-related indices.

Actinic keratosis with severe dysplasia and Bowen disease represent distinct pathways of intraepidermal squamous neoplasia: an immunohistochemical study

Intraepidermal squamous neoplasia is a precursor to invasive cutaneous squamous cell carcinoma. The most common type of intraepidermal squamous neoplasia is actinic keratosis (AK), although there is compelling clinicopathological evidence of a second distinct pattern of squamous dysplasia termed Bowen disease (BD). The distinction between these pathways of dysplasia has been inconsistently delineated in the literature.To further investigate the biological differences between AK and BD, a cohort of cases of intraepidermal squamous dysplasia including AK with mild/moderate dysplasia (n=26), AK with severe dysplasia (n=21) and BD (n=47) was prospectively collected. Immunohistochemistry was utilised to assess the protein expression of major tumour suppressor genes including p16, RB1 and p53.Most cases of BD showed complete loss of RB-1 (∼80%), strong and diffuse positive staining for p16 (∼80%), and mutant pattern (diffusely positive or completely negative) of p53 (∼79%). However, lesions of AK showed loss of RB-1 in only 6%, strong and diffuse positive staining for p16 in 4% and mutant pattern of p53 in 85% of case (p<0.001).The statistically significant difference in RB-1 and p16 expression between AK and BD confirms that the two morphologically distinct types of intraepidermal squamous neoplasia differ in protein expression of major tumour suppressor genes and provide evidence that they represent two distinct genomic pathways of squamous neoplasia. Recognition of clinical and genomic differences between different pathways of squamous neoplasia could potentially have an important role in predicting the biological behaviour and treatment of advanced tumours arising from these precursor lesions.

Contribution of Cancer-Specific Protein Coronas to the Pro-Tumor Effects of Nanoplastics through Enhanced Cellular Interactions.

The potential impact of nanoplastics (NPs) on human carcinogenic processes is a matter of growing concern, particularly in light of the global plastic pollution crisis. Although the potential effects of NPs on human health have been well investigated, many uncertainties remain regarding their role in tumor behavior. Upon exposure, NPs can enter the bloodstream and are prone to interacting with plasma proteins to form a protein corona (PC), which can influence their interactions with cancer cells. However, how the PCs adsorbed on NPs affect the particle-to-tumor cell interaction and their effect on the tumor biological behavior remain unclear. To better understand the formation of PCs following NPs exposure in the bloodstream under various clinical conditions, we investigated the PC compositions of NPs derived from thyroid cancer (TC) patients and healthy volunteers. Our data revealed a significant enrichment of fibrinogen in the PCs formed on NPs derived from TC patient plasma, which in turn accelerated the endocytosis of NPs into TC cells. In addition, the uptake pathway of NPs into TC cells differed substantially between the two groups studied due to the different PC compositions in cancer patients and healthy individuals. Moreover, intriguingly alterations in the PCs induced by the clinical pathology status were also found to promote NPs engulfment by human macrophages, resulting in potent pro-inflammatory effects, in turn exerting pro-tumor effects. These findings emphasize the importance of considering the significance of a realistic biological identity on NPs and their interactions with cancer cells and also pinpoint the implications of the carcinogenesis outcomes of NPs exposure in humans.

Research progress on the molecular structure, function, and application in tumor therapy of zinc transporter ZIP4.

ZIP4, a pivotal member of the ZIP family, is the causative gene for the hereditary disorder AE (acrodermatitis enteropathica) in humans, and plays an essential role in regulating zinc ion balance within cells. While research on the molecular structure of ZIP4 continues, there remains a lack of full understanding regarding the stereo-structural conformation of ZIP4 molecules. Currently, there are two hypotheses concerning the transport of zinc ions into the cytoplasm by ZIP4, with some contradictions between experimental studies. Recent investigations have revealed that ZIP4 is involved in tumor growth, metastasis, drug tolerance, and various other processes. Most studies suggest that ZIP4 regulates the malignant biological behavior of tumors through zinc ions as a second messenger: however, latest research has identified that ZIP4 itself binds to Ephrin-B1 to regulate tumor metastasis. This review provides a comprehensive summary of the molecular structure of ZIP4 and its mechanism for transporting zinc ions while also exploring mutual regulation between zinc ions and ZIP4. Furthermore, it summarizes recent research progress on the role of ZIP4 in tumors and discusses its potential as a target for anticancer therapy based on an extensive analysis of research findings. These insights can guide future investigations into the role of ZIP4 in tumors.

Role of Advanced Magnetic Resonance Imaging in Differentiating among Glioma Subtypes and Predicting Tumor-Proliferative Behavior

Abstract Objective Gliomas are a devastating and heterogeneous group of primary brain tumors. Previously, the source of glioma was undetermined. Recent literature indicates that neural stem cells, or progenitors, are proposed to be the source of glioma. The prognosis of different types of gliomas differs due to their various biological tissue types. Besides the histological grade, the two useful immunohistochemistry markers that show the tumor's biological behavior are isocitrate dehydrogenase (IDH) labeling and the Ki-67 labeling index. We sought to determine the magnetic resonance imaging (MRI) characteristics associated with IDH mutational status and ascertain whether MRI combined with IDH mutational status, can better predict the clinical outcomes of gliomas. Materials and Methods This period study was conducted in the Department of Radiology, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu, India for 5 years (May 2016–May 2021). The study cohort included 30 patients diagnosed with gliomas who underwent preoperative MRI followed by surgical resection and histopathological examination. Preoperative MRI images were done to assess qualitative tumor characteristics such as location, margin of tumor, extent, cortical involvement, cystic component, mineralization or hemorrhage, and contrast enhancement. Discussion Differences in MRI features between IDH-mutant (MT) and IDH-wild-type (WT) groups were analyzed using the chi-square test for categorical variables and the Mann–Whitney U test for continuous variables. Statistical analysis was conducted using SPSS software. Results Among the 30 patients evaluated, 18 had IDH-WT and 12 had IDH-MT type gliomas. Male predominance (73.33%) was noted in our study. Brainstem location, indistinct borders (83.33%), less cortical involvement (72.22%), less cystic changes (88.89%), more area of necrotic component (44.44%), significantly increased choline/creatine (Cho/Cr) ratio, and choline/N-acetyl aspartate (Cho/NAA) ratio favors IDH-WT tumors. Positive T2-fluid-attenuated inversion recovery mismatch sign is more frequently seen in IDH-MT (7/12; 58.33%) tumors than in IDH-WT (4/18; 22.22%) tumors. Whereas well-defined contours (66.67%), more cortical involvement (83.33%), more cystic changes (58.33%), and less area of necrotic component favor IDH-MT type tumors. Conclusion MRI is a very promising and valuable tool for differentiating among glioma subtypes and predicting tumor-proliferative behavior in glioma cases. The combination of MRI characteristics with IDH mutation status enhances the predictive accuracy for clinical outcomes in glioma patients. This approach could potentially guide treatment planning and improve prognostic assessments.

An integrative analysis based on multiple cell death patterns identifies an immunosuppressive subtype and establishes a prognostic signature in lower-grade glioma

Background Cell death modulates the biological behaviors of tumors. However, the comprehensive role of the multiple forms of cell death in lower-grade glioma (LGG) is unknown. Methods We collected the transcriptional data of LGG patients from public repositories to comprehensively examine six cell death patterns (autophagy, apoptosis, cuproptosis, necroptosis, ferroptosis, and pyroptosis) in LGG samples and systematically correlated these patterns with patient survival, underlying biological processes, and drug sensitivity using serial bioinformatics analysis, clinical sample validation and in vitro assays. Results We identified and independently validated three reproducible cell death-based clusters associated with distinct clinical outcomes and tumor microenvironment characteristics. The Tumor Immune Dysfunction and Exclusion algorithm was applied for predicting how these three clusters would respond to immune checkpoint blockade (ICB) therapy; we found potential resistance of cluster B to ICB therapy. We also performed drug screening to identify cluster-specific drugs. Furthermore, a scoring system, designated as the CDPM score, was developed to estimate the cell death patterns of patients with LGG; this system could predict both LGG patients’ prognosis and immunotherapy efficacy. By performing multiplex immunofluorescence staining, we validated the correlations of GNAL expression with the molecular and clinical features of LGG in an independent LGG cohort. Finally, in vitro assays showed that GNAL promoted apoptosis and inhibited the proliferation of LGG cells. Conclusion The new cell death-based subtype system indicates several features of LGG biology and reveals novel insights into the use of precision medicine for treating LGG. The CDPM score could be used to predict the immunotherapy response and prognosis of LGG patients; moreover, it could indicate a novel direction for improving LGG management.

The role of short-chain fatty acid metabolism in the pathogenesis, diagnosis and treatment of cancer.

Short-chain fatty acids (SCFAs), which are saturated fatty acids consisting of six or fewer carbon atoms, have been found to be closely associated with the biological behavior of malignant tumors. This manuscript provides a comprehensive review on the role of SCFAs in regulating cell cycle, apoptosis, tumor angiogenesis, epithelial-mesenchymal transition, protein regulatory pathways, and histone regulation in promoting the development of malignant tumors. Furthermore, we discuss the potential therapeutic strategies targeting SCFAs for treating malignant tumors. This review offers a theoretical foundation for investigating the mechanisms by which SCFAs impact malignant tumors and provides insights into developing novel treatment targets.

MiR-155-5p regulates autophagy and apoptosis of glioma cells through RICTOR.

Glioma characterized by the high degree of drug resistance and the poor prognosis is the most common primary malignant tumors of the brain. And miRNA is involved in a variety of biological behaviors of tumors, enhancing or inhibiting the occurrence and development of tumors. Therefore, the present study aims to explore whether miR-155-5p can regulate autophagy and apoptosis of glioma through RICTOR. The significantly differential gene miR-155-5p was identified from the Gene Expression Omnibus (GEO; http://www.ncbi.nlm.nih.gov/geo) databases GSE165937 and GSE138764 using bioinformatics analysis, and its expression was validated by quantitative real-time polymerase chain reaction (qRT-PCR). The putative target genes of miR-155-5p were predicted through interrogation of relevant databases, followed by identification of key target genes. Subsequently, core target genes were selected for functional enrichment analysis. The U87MG cell line was utilized as the experimental model and divided into Negative Control1 (NC1) group, Mimic group, Negative Control2 (NC2) group, Inhibitor group, and NC + 3-methyladenine (3-MA) group. The expression levels of miR-155-5p, RICTOR, P62, LC-3, Bax, Bcl-2, and Caspase-3 were assessed using qRT-PCR, cellular fluorescence imaging, and Western blotting; while apoptosis in the U87MG cell line was evaluated via flow cytometry. The results showed that miR-155-5P was highly expressed in glioma cells, which could inhibit the expression of Bax, Caspase-3, LCII/LCI and Beclin-1, and increase the expression of Bcl2 and P62. Flow cytometry and cell fluorescence were used to verify the above results. Moreover, when U87MG cells treated with miR-155-5p inhibitor were inhibited by 3-MA, the results showed that miR-155-5p enhanced the anti-apoptotic ability of U87MG cells by regulating autophagy. In addition, the bioinformatics results show that miR-155-5p survival prognosis in glioma into a strong negative correlation, while the survival prognosis of RICTOR in glioma showed a strong positive correlation. The core target genes Kyoto Encyclopedia of Genes and Genomes (KEGG) mainly occurred in PI3K-AKT signaling pathway; in addition, qRT-PCR and Western blot confirmed the regulatory effect of miR-155-5P on RICTOR. MiR-155-5p regulates autophagy and apoptosis-related proteins in glioma cells through RICTOR, affecting the occurrence and development of glioma.

The MCIB Model: A Novel Theory for Describing the Spatial Heterogeneity of the Tumor Microenvironment

The tumor microenvironment (TME) can be regarded as a complex and dynamic microecosystem generated by the interactions of tumor cells, interstitial cells, the extracellular matrix, and their products and plays an important role in the occurrence, progression and metastasis of tumors. In a previous study, we constructed an IEO model (prI-, prE-, and pOst-metastatic niche) according to the chronological sequence of TME development. In this paper, to fill the theoretical gap in spatial heterogeneity in the TME, we defined an MCIB model (Metabolic, Circulatory, Immune, and microBial microenvironment). The MCIB model divides the TME into four subtypes that interact with each other in terms of mechanism, corresponding to the four major links of metabolic reprogramming, vascular remodeling, immune response, and microbial action, providing a new way to assess the TME. The combination of the MCIB model and IEO model comprehensively depicts the spatiotemporal evolution of the TME and can provide a theoretical basis for the combination of clinical targeted therapy, immunotherapy, and other comprehensive treatment modalities for tumors according to the combination and crosstalk of different subtypes in the MCIB model and provide a powerful research paradigm for tumor drug-resistance mechanisms and tumor biological behavior.

Surgical Treatment of Primary Mast Cell Tumor in Mucosal Surface of Lower Lip in a Dog: A Case Report

Introduction: Mast cell tumors (MCTs) have been described as a form of cancer affecting a specific type of blood cell that typically plays a role in the body's reaction to allergens and inflammatory processes. The MCTs have been classified as skin tumors in dogs which can also affect other areas of the body, such as the spleen, liver, gastrointestinal tract, and bone marrow. The present study investigated the clinical and histological signs, biological behavior, and treatment of primary oral mast cell tumors. Case report: A 3-year-old neutered female, weighing 18 kg and classified as a medium mixed breed, was referred to a veterinary clinic in Mashhad (Iran) due to the presence of a pink, lobulated mucosal mass located on the internal surface of her lower lip. Although the vital signs were normal, clinical examination, radiology, and an incisional biopsy were performed from the lesion site under general anesthesia for histology study. Histopathological features were similar to those of mastocytoma in this case. On presentation, no concurrent mass was found on other sides of the body. Mandibular lymph nodes were not enlarged; however, the incisor teeth of the mandible were loosed. Accordingly, the primary oral MCTs were diagnosed. The surgery was done and After a follow-up period of 150 days post-excisional surgery for a Mast cell tumor, the patient remained alive and exhibited no visible signs of tumor recurrence or surgical complications. Conclusion: The current case report defined a primary Mast cell tumor with slow tumor growth and without metastasis in the mucosal surface of the lower lip in a dog treated by complete excisional surgery only, unlike some previous studies of primary oral MCTs in dogs with aggressive biological behaviors.

Progress of Cancer Stem Cells in Retinoblastoma.

The theory of cancer stem cells is a breakthrough discovery that offers exciting possibilities for comprehending the biological behavior of tumors. More and more evidence suggests that retinoblastoma cancer stem cells promote tumor growth and are likely to be the origin of tumor formation, drug resistance, recurrence, and metastasis. At present, some progress has been made in the verification, biological behavior, and drug resistance mechanism of retinoblastoma cancer stem cells. This article aims to review the relevant research and explore future development direction.

CT-based radiomic consensus clustering association with tumor biological behavior in clinical stage IA adenocarcinoma: a retrospective study.

Research has demonstrated that radiomics models are capable of forecasting the characteristics of lung cancer. Nevertheless, due to radiomics' poor interpretability, its applicability in clinical settings remains restricted. This investigation sought to verify the correlation between radiomics features (RFs) and the biological behavior of clinical stage IA adenocarcinomas. A retrospective analysis was conducted on patients diagnosed with clinical stage IA lung adenocarcinoma who underwent resection between May 2005 and December 2018. Detailed radiomics examination of the primary tumor was carried out utilizing preoperative computed tomography (CT) images. Subsequently, patients were grouped based on their RFs using consensus clustering, enabling comparison of tumor biological characteristics among the clusters. Survival disparities among the clusters were evaluated through Kaplan-Meier and Cox analyses. A consensus cluster analysis was performed on 669 patients [median age, 58 years; interquartile range (IQR), 50-64 years, 257 males, 412 females], and three distinct clusters were identified. Cluster 2 was associated with radiological solid adenocarcinoma [119 of 324 (36.7%), P<0.001], larger tumors with median tumor size of 2.1 cm with IQR of 1.7 to 2.5 cm (P<0.001), central tumor [91 of 324 (28.1%), P=0.002], pleural invasion [87 of 324 (26.9%), P<0.001], occult lymph node metastasis (ONM) [106 of 324 (32.7%), P<0.001], and a higher frequency of metastasis or recurrence [62 of 324 (19.1%), P<0.001]. The frequency of histological grade 3 was the highest in Cluster 3 [8 of 34 (23.5%), P<0.001]. Cluster 1 was associated with pure ground glass nodules (pGGNs) [184 of 310 (59.4%), P<0.001], smaller tumors with median tumor size of 1.1 cm with IQR of 0.8 to 1.4 cm (P<0.001), no pleural invasion [276 of 310 (89.0%), P<0.001], histological grade 1 [114 of 248 (46.0%), P<0.001], ONM negative [292 of 310 (94.2%), P<0.001], and a lower rate of metastasis or recurrence [298 of 310 (96.1%), P<0.001]. Differences in tumor biological behavior were detected among consensus clusters based on the RFs of clinical stage IA adenocarcinoma.

Identification and experimental verification of a biomarker by combining the unfolded protein response with the immune cells in colon cancer.

The unfolded protein response (UPR) is associated with immune cells that regulate the biological behavior of tumors. This article aims to combine UPR-associated genes with immune cells to find a prognostic marker and to verify its connection to the UPR. Univariate cox analysis was used to screen prognostically relevant UPRs and further screened for key UPRs among them by machine learning. ssGSEA was used to calculate immune cell abundance. Univariate cox analysis was used to screen for prognostically relevant immune cells. Multivariate cox analysis was used to calculate UPR_score and Tumor Immune Microenvironment score (TIME_score). WGCNA was used to screen UPR-Immune-related (UI-related) genes. Consensus clustering analysis was used to classify patients into molecular subtype. Based on the UI-related genes, we classified colon adenocarcinoma (COAD) samples by cluster analysis. Single-cell analysis was used to analyze the role of UI-related genes. We detected the function of TIMP1 by cell counting and transwell. Immunoblotting was used to detect whether TIMP1 was regulated by key UPR genes. Combined UPR-related genes and immune cells can determine the prognosis of COAD patients. Cluster analysis showed that UI-related genes were associated with clinical features of COAD. Single-cell analysis revealed that UI-related genes may act through stromal cells. We defined three key UI-related genes by machine learning algorithms. Finally, we found that TIMP1, regulated by key genes of UPR, promoted colon cancer proliferation and metastasis. We found that TIMP1 was a prognostic marker and experimentally confirmed that TIMP1 was regulated by key genes of UPR.

Circ-CDK8 regulates SLC7A11-mediated ferroptosis by inhibiting miR-615-5p to promote progression in oral squamous cell carcinomas.

Introduction: Ferroptosis is a new mode of programmed cell death distinct from necrosis, apoptosis, and autophagy, induced by iron-ion-dependent lipid peroxide accumulation. Circular RNAs are a class of endogenous non-coding RNAs that regulate the biological behavior of tumors. However, the role of circ-CDK8 in regulating ferroptosis, migration, and invasion of oral squamous cell carcinoma (OSCC) remains unknown. Methods: The effect of circ-CDK8 on OSCC cell ferroptosis, migration, and invasion was evaluated using CCK-8, wound healing, transwell, reactive oxygen species (ROS), malondialdehyde (MDA), and GSH assays and Western blotting. Bioinformatics analyses and luciferase reporter assays were performed and revealed targeted relationships between circ-CDK8 and miR-615-5p, miR-615-5p and SLC7A11. Interference with circ-CDK8 expression reduced SLC7A11 expression by sponging miR-615-5p, suppressed OSCC cell migration and invasion, and promoted ferroptosis by increasing ROS, MDA, and iron levels and decreasing GSH and GPX4 levels in OSCC cells. Furthermore, in vivo, animal experiments confirmed that circ-CDK8 interference inhibited OSCC cell proliferation and SLC7A11 expression. Results: Collectively, this study revealed a novel strategy to upregulate erastin-induced ferroptosis in OSCC cells via the circ-CDK8/miR-615-5p/SLC7A11 axis, providing new insights into OSCC and a potential therapeutic strategy for OSCC.

Unveiling the multifaceted roles of microRNAs in extracellular vesicles derived from mesenchymal stem cells: implications in tumor progression and therapeutic interventions.

Mesenchymal stem/stromal cells (MSCs) have the capacity to migrate to tumor sites in vivo and transmit paracrine signals by secreting extracellular vesicles (EVs) to regulate tumor biological behaviors. MSC-derived EVs (MSC-EVs) have similar tumor tropism and pro- or anti-tumorigenesis as their parental cells and exhibit superior properties in drug delivery. MSC-EVs can transfer microRNAs (miRNAs) to tumor cells, thereby manipulating multiple key cancer-related pathways, and further playing a vital role in the tumor growth, metastasis, drug resistance and other aspects. In addition, tumor cells can also influence the behaviors of MSCs in the tumor microenvironment (TME), orchestrating this regulatory process via miRNAs in EVs (EV-miRNAs). Clarifying the specific mechanism by which MSC-derived EV-miRNAs regulate tumor progression, as well as investigating the roles of EV-miRNAs in the TME will contribute to their applications in tumor pharmacotherapy. This article mainly reviews the multifaceted roles and mechanism of miRNAs in MSC-EVs affecting tumor progression, the crosstalk between MSCs and tumor cells caused by EV-miRNAs in the TME. Eventually, the clinical applications of miRNAs in MSC-EVs in tumor therapeutics are illustrated.

Construction and validation of a prognostic model for overall survival time of patients with ovarian cancer by metabolism-related genes.

Ovarian cancer is a female-specific malignancy with high morbidity and mortality. The metabolic reprogramming of tumor cells is closely related to the biological behavior of tumors. The prognostic signature of the metabolism-related gene (MRGs) was established by LASSO-Cox regression analysis. The prognostic signature of MRGs was also prognosticated in each clinical subgroup. These genes were subjected to functional enrichment analysis and tissue expression exploration. Analysis of the MRG prognostic signature in terms of immune cell infiltration and antitumor drug susceptibility was also performed. A MRG prognostic signature including 21 genes was established and validated. Most of the 21 MRGs were expressed at different levels in ovarian cancer than in normal ovarian tissue. The enrichment analysis suggested that MRGs were involved in lipid metabolism, membrane organization, and molecular binding. The MRG prognostic signature demonstrated the predictive value of overall survival time in various clinical subgroups. The monocyte, NKT, Tgd and Tex cell scores showed differences between the groups with high- and low-risk score. The antineoplastic drug analysis we performed provided information on ovarian cancer drug therapy and drug resistance. In vitro experiments verified that PLCH1 in 21 MRGs can regulate the apoptosis and proliferation of ovarian cancer cells. This metabolism-related prognostic signature was a potential prognostic factor in patients with ovarian cancer, demonstrating high stability and accuracy.