Tumor Progression Research Articles

Inflammation and Related Signaling Pathways in Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy, and inflammatory signaling is involved in its pathogenesis. Cytokines exert a robust effect on the progression of AML and affect survival outcomes. The dysregulation in the cytokine network may foster a pro-tumorigenic microenvironment, increasing leukemic cell proliferation, decreasing survival and driving drug resistance. The dominance of pro-inflammatory mediators such as IL-11β, TNF-α and IL-6 over anti-inflammatory mediators such as TGF-β and IL-10 has been implicated in tumor progression. Additionally, inflammatory cytokines have favored certain populations of hematopoietic stem and progenitor cells with mutated clonal hematopoiesis genes. This article summarizes current knowledge about inflammatory cytokines and signaling pathways in AML, their modes of action and the implications for immune tolerance and clonal hematopoiesis, with the aim of finding potential therapeutic interventions to improve clinical outcomes in AML patients.

Unveiling the role of TGF-β signaling pathway in breast cancer prognosis and immunotherapy

IntroductionThe TGF-β signaling pathway (TSP) is pivotal in tumor progression. Nonetheless, the connection between genes associated with the TSP and the clinical outcomes of breast cancer, as well as their impact on the tumor microenvironment and immunotherapeutic responses, remains elusive.MethodsBreast cancer transcriptomic and single-cell sequencing data were obtained from the The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. We identified 54 genes associated with the TSP from the Molecular Signatures Database (MSigDB) and analyzed both data types to evaluate TSP activity. Using weighted gene co-expression network analysis (WGCNA), we identified modules linked to TSP activity. To assess patient risk, we used 101 machine learning algorithms to develop an optimal TGF-β pathway-related prognostic signature (TSPRS). We then examined immune activity and response to immune checkpoint inhibitors and chemotherapy in these groups. Finally, we validated ZMAT3 expression levels clinically and confirmed its relevance in breast cancer using CCK-8 and migration assays.ResultsAt the single-cell level, TSP activity was most notable in endothelial cells, with higher activity in normal tissues compared to tumors. TSPRS was developed. This signature's accuracy was confirmed through internal and external validations. A nomogram incorporating the TSPRS was created to improve prediction accuracy. Further studies showed that breast cancer patients categorized as low-risk by the TSPRS had higher immune phenotype scores and more immune cell infiltration, leading to better prognosis and enhanced immunotherapy response. Additionally, a strong link was found between the TSPRS risk score and the effectiveness of anti-tumor agents. Silencing the ZMAT3 gene in the TSPRS significantly reduced the proliferation and invasiveness of breast cancer cells.DiscussionOur study developed a TSPRS, which emerges as a potent predictive instrument for the prognosis of breast cancer, offering novel perspectives on the immunotherapeutic approach to the disease.

CARMIL1-AA selectively inhibits macropinocytosis while sparing autophagy.

Macropinocytosis is reported to fuel tumor growth and drug resistance by allowing cancer cells to scavenge extracellular macromolecules. However, accurately defining the role of macropinocytosis in cancer depends on our ability to selectively block this process. 5-(N-ethyl-N-isopropyl)-amiloride (EIPA) is widely used to inhibit macropinocytosis but affects multiple Na+/H+ exchangers (NHE) that regulate cytoplasmic and organellar pH. Consistent with this, we report that EIPA slows proliferation to a greater extent than can be accounted for by macropinocytosis inhibition and triggers conjugation of ATG8 to single membranes (CASM). Knocking down only NHE1 would not avoid macropinocytosis-independent effects on pH. Moreover, contrary to published reports, NHE1 loss did not block macropinocytosis in multiple cell lines. Knocking down CARMIL1 with CRISPR-Cas9 editing limited macropinocytosis, but only by 50%. In contrast, expressing the CARMIL1-AA mutant inhibits macropinocytosis induced by a wide range of macropinocytic stimuli to a similar extent as EIPA. CARMIL1-AA expression did not inhibit proliferation, highlighting the shortcomings of EIPA as a macropinocytosis inhibitor. Importantly, autophagy, another actin dependent, nutrient-producing process, was not affected by CARMIL1-AA expression. In sum, constitutive or inducible CARMIL1-AA expression reduced macropinocytosis without affecting proliferation, RAC activation, or autophagy, other processes that drive tumor initiation and progression. [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text].

Clinical outcomes of microwave ablation for solitary T1N0M0 papillary thyroid carcinoma: a more than 5-year follow-up study.

This study aimed to evaluate the long-term efficacy and safety of microwave ablation (MWA) for solitary T1N0M0 papillary thyroid carcinoma (PTC) and compare them between T1a and T1b disease. This retrospective study included 136 patients with solitary T1N0M0 PTC who were treated with MWA and followed up for more than 5 years. Outcomes were compared between patients with T1a and T1b disease. The primary outcomes were disease progression and disease-free survival (DFS). The secondary outcomes included the volume reduction rate (VRR), the rate of complete disappearance, and complications. During a mean follow-up period of 70.6 ± 10.5 months, the overall disease progression rate was 5.88%. The incidences of lymph node metastases (LNMs) and new tumors were 2.21% and 5.15%, respectively. No patient was diagnosed with local recurrence, distant metastasis, or death due to PTC. There were no significant differences between the T1a and T1b groups in terms of disease progression (3.81% vs 12.90%, p = 0.15), LNMs (1.90% vs 3.23%, p = 0.54), or new tumors (2.86% vs 12.90%, p = 0.08). The 5-year DFS rate was 94.85%, the VRR was 99.7% ± 2.0%, and 97.79% of the tumors disappeared. Hoarseness occurred in five patients (3.68%). MWA is a long-term effective and safe option for patients with solitary T1N0M0 PTC, providing a minimally invasive alternative for those who refuse surgery or active surveillance. Question MWA, as a minimally invasive alternative for treating PTC, lacks comparison with surgical resection and active surveillance. Findings MWA resulted in overall disease progression in 5.88% of patients with solitary T1N0M0 PTC over more than 5 years of follow-up. Clinical relevance MWA is a safe, effective, and minimally invasive treatment for solitary T1N0M0 PTC, with high DFS rates and low complication rates, benefiting patients seeking alternatives to surgery or active surveillance.

Pan-immune-inflammation value predicts immunotherapy response and reflects local antitumor immune response in rectal cancer.

The pan-immune-inflammation value reflects the systemic inflammatory response, and tumor-infiltrating lymphocytes indicate a local immune response in rectal cancer. However, the association between systemic inflammatory response, as indicated by the pan-immune-inflammation value, and local immune responses in rectal cancer remains unclear. This study analyzed 915 treatment-naïve rectal cancer patients from the Peking Union Medical College Hospital and PLA General Hospital (PLAGH) cohorts who underwent radical surgery to investigate the relationship between the pan-immune-inflammation value and immune responses. Lower pan-immune-inflammation value was significantly associated with improved disease-free survival and cancer-specific survival. Multivariate Cox regression models identified the pan-immune-inflammation value as an independent prognostic factor. In the PLAGH cohort, patients with low pan-immune-inflammation values had higher immune cell levels, activated immune pathways, and increased expression of immune checkpoint genes according to RNA sequencing. Hematoxylin and eosin staining and immunohistochemical analysis revealed that lower pan-immune-inflammation value was associated with higher tumor-infiltrating lymphocyte density, more mature tertiary lymphoid structures, increased CD8+ T cells, and elevated human lymphocyte antigen class I expression. Conversely, patients with high pan-immune-inflammation values exhibited pathways linked to tumor progression, such as angiogenesis, epithelial-mesenchymal transition, hypoxia, KRAS signaling, and TGF-ß signaling. Among patients receiving anti-PD-1 therapy, responders had low pre- and post-treatment pan-immune-inflammation values. The pan-immune-inflammation value is a reliable marker associated with distinct immune microenvironment characteristics and can effectively predict disease-free survival, cancer-specific survival, and response to immunotherapy.

Nanocarriers for Delivery of Anticancer Drugs: Current Developments, Challenges, and Perspectives

Cancer, the most common condition worldwide, ranks second in terms of the number of human deaths, surpassing cardiovascular diseases. Uncontrolled cell multiplication and resistance to cell death are the traditional features of cancer. The myriad of treatment options include surgery, chemotherapy, radiotherapy, and immunotherapy to treat this disease. Conventional chemotherapy drug delivery suffers from issues such as the risk of damage to benign cells, which can cause toxicity, and a few tumor cells withstand apoptosis, thereby increasing the likelihood of developing tolerance. The side effects of cancer chemotherapy are often more pronounced than its benefits. Regarding drugs used in cancer chemotherapy, their bioavailability and stability in the tumor microenvironment are the most important issues that need immediate addressing. Hence, an effective and reliable drug delivery system through which both rapid and precise targeting of treatment can be achieved is urgently needed. In this work, we discuss the development of various nanobased carriers in the advancement of cancer therapy—their properties, the potential of polymers for drug delivery, and recent advances in formulations. Additionally, we discuss the use of tumor metabolism-rewriting nanomedicines in strengthening antitumor immune responses and mRNA-based nanotherapeutics in inhibiting tumor progression. We also examine several issues, such as nanotoxicological studies, including their distribution, pharmacokinetics, and toxicology. Although significant attention is being given to nanotechnology, equal attention is needed in laboratories that produce nanomedicines so that they can record themselves in clinical trials. Furthermore, these medicines in clinical trials display overwhelming results with reduced side effects, as well as their ability to modify the dose of the drug.

Single-cell transcriptome sequencing and analysis provide a new approach for the treatment of small cell neuroendocrine carcinoma of the cervix.

Small cell neuroendocrine carcinoma of the cervix (SCNECC) is a rare gynecologic malignant tumor, which is lack of systematic research. In order to investigate its molecular characteristics, origin and pathogenesis, single-cell transcriptome sequencing (scRNA-Seq) of SCNECC were performed for the first time, the cellular and molecular landscape was revealed and the key genes for clinical prognosis were screened. This article initially performed the scRNA-Seq on a tumor tissue sample from a SCNECC patient, combined with scRNA-Seq data from a healthy cervical tissue sample downloaded from public database, the single-cell transcriptome landscape was constructed. Then, we investigated the cell types, intratumoral heterogeneity, characteristics of tumor microenvironment and potential predictive markers of SCNECC. We identified two malignant cell populations, tumor stem cells and malignant carcinoma cells, and revealed two tumor progression pathways of SCNECC. By analyzing gene expression levels in the pathophysiology of SCNECC, we found that the expression levels of ERBB4 and NRG1, as well as the expression profile of mTOR signaling pathway mediated by them, were significantly upregulated in malignant carcinoma cells. In addition, we also found that carcinoma cells were able to stimulate malignant cell proliferation through FN1 signaling pathway. The immune cells were in a stress state, with T cell depletion, macrophage polarization and mast cell glycolysis, these results suggested that carcinoma cells could interfere immune response and promote tumor escape through MIF, TGFb and other immunosuppressive related signaling pathways. This study revealed the mechanism of genesis and progression in SCNECC and the related important signaling pathways, such as mTOR, and provided new insights into the treatment of SCNECC.

CBX3 Downregulates HLTF to Activate PI3K/AKT Signaling Promoting Cholangiocarcinoma.

Cholangiocarcinoma (CCA) is an aggressive cancer with poor response to chemotherapy or radiation, necessitating novel therapeutic approaches. Epigenetic regulation, which is reversible, plays a significant role in cancer progression. CBX3 (HP1γ), a key heterochromatin protein, regulates gene expression by interacting with histone H3 lysine 9 trimethyl (H3K9me3) markers. While CBX3 is linked to tumor progression in various cancers, its role in CCA remains unclear. This study reveals that CBX3 and H3K9me3 enrich the HLTF promoter, a gene involved in chromatin remodeling and DNA repair. HLTF is often inactivated by hypermethylation in other cancers, suggesting tumor-suppressive properties. Depleting CBX3 in CCA cells elevates HLTF expression, reducing proliferation, while HLTF silencing reverses this effect. Furthermore, HLTF overexpression inhibits PI3K-AKT signaling activated by CBX3. These findings suggest CBX3 promotes CCA progression by suppressing HLTF expression.

Photoacoustic polydopamine-indocyanine green (PDA-ICG) nanoprobe for detection of senescent cells

Cellular senescence is considered an important tumour suppression mechanism in response to damage and oncogenic stress in early lesions. However, when senescent cells are not immune-cleared and persist in the tumour microenvironment, they can drive a variety of tumour-promoting activities, including cancer initiation, progression, and metastasis. Additionally, there is compelling evidence demonstrating a direct connection between chemo(radio)therapy-induced senescence and the development of drug resistance and cancer recurrence. Therefore, detection of senescent cells in tissues holds great promise for predicting cancer occurrence earlier, assessing tumour progression, aiding patient stratification and prognosis, and informing about the efficacy of potential senotherapies. However, effective detection of senescent cells is limited by lack of biomarkers and readout strategies suitable for in vivo clinical imaging. To this end, a nanoprobe composed of biocompatible polydopamine (PDA) nanoparticle doped with FDA-approved indocyanine green (ICG) dye, namely PDA-ICG, was designed as a contrast agent for senescence detection using photoacoustic imaging (PAI). In an in vitro model of chemotherapy-induced senescence, PDA-ICG nanoprobe showed an elevated uptake in senescent cells relative to cancer cells. In addition to its improved photostability, 2.5-fold enhancement in photoacoustic signal relative to ICG was observed. Collectively, the results indicate that the PDA-ICG nanoprobe has the potential to be used as a contrast agent for senescence detection of chemotherapy-induced senescence using PAI.

Long-term outcomes of active surveillance for low-risk papillary thyroid carcinoma: Progression patterns and tumor calcification.

Active surveillance (AS) for low-risk papillary thyroid carcinoma (PTC) is acknowledged as a valid management strategy. While older age is identified as a favorable factor for progression, long-term evidence is scarce and lifelong monitoring has been deemed essential. This study investigated progression patterns and tumor calcification under long-term AS and explored the possibility of ending follow-up. A total of 650 patients with low-risk PTC who chose AS were enrolled. Progression was defined as either tumor enlargement (≥3mm from initiation) or development of clinically apparent lymph node metastasis. The median observation period was 8years; 45.2% were under surveillance for ≥10years. Overall, 80 patients (12.3%) exhibited progression. Median age and observation period at the time of progression were 55 and 4years, respectively. Only 2 patients showed progression after 15years of follow-up and 5 patients showed progression after reaching 80years old. Among 71 patients experiencing tumor enlargement, surgery was performed immediately in 32 patients. The remaining 39 patients continued surveillance, but only 5 demonstrated ongoing enlargement thereafter. Of 40 surgeries due to progression, 36 were conducted within the first 10years. The degree of calcification correlated with age and observation periods. No progression occurred after the development of rim calcification. Progression during AS was extremely rare in older patients with long-term surveillance and in tumors with rim calcification. It may be feasible to consider ending scheduled surveillance visits for these patients. Instances of progression halting after enlargement are not uncommon.

Immunohistochemical Staining Properties of Osteopontin and Ki-67 in Feline Meningiomas

The high recurrence rate of feline meningioma despite the generally benign histomorphology warrants additional markers of clinical aggressiveness. The Ki-67 index is commonly used as prognostic marker for meningioma recurrence in people. Osteopontin (OPN) is a protein involved in tumor progression and may be a potential malignancy marker. To date, osteopontin expression has not been investigated in feline meningioma. The aim of this study was to evaluate the extent of Ki-67 and osteopontin immunostaining of feline meningioma and to find possible associations with WHO (World Health Organization) grades and subtypes. Fifty-three feline meningioma samples were graded according to the human WHO classification and underwent immunohistochemical examination for Ki-67 and OPN. Fifty samples were classified as WHO grade I and three as WHO grade II. The mean Ki-67 ratio was 9.19 ± 9.47. Osteopontin expression was correspondingly high with a mean OPN IHC score of 150.17 (0–242.8), and a median Allred score of 7 (0–8). There was no significant correlation with Ki-67 index, osteopontin expression, WHO grades, or subtypes. The overall high expressions of osteopontin and Ki-67 may help explain the tendency for recurrence of feline meningioma. The human WHO grading system may not be sufficient to accurately estimate the clinical behavior of meningioma in this species.

Identification of gasdermin B function in the progression of renal clear cell carcinoma by a pan-cancer analysis

The Gasdermin (GSDM) protein family is critically involved in pyroptosis, which participates in the onset and progression of human malignancies. The exact role and impact of the GSDM family genes in various malignancies, particularly renal clear cell carcinoma (KIRC), is still uncertain. The present results indicated GSDMB gene expression significantly upregulated in individuals with KIRC, whose diagnostic effectiveness was confirmed through ROC analysis. Kaplan–Meier analysis also revealed KIRC patients had poor survival prognosis. The high expression of GSDMB served as an independent risk factor for overall survival (OS) in KIRC, based on multivariate cox analysis for confirmation. A nomogram based on GSDMB expression and clinical characteristics displayed remarkable diagnostic effectiveness for KIRC. Collectively, these findings may shed light on functions of GSDM family genes in tumor progression and offer new directions for future research into their potential as therapeutic targets in various types of tumors. Furthermore, the outcomes of this research highlighted that the prediction of treatment responses in KIRC patients may get improved through in-depth exploration into the impact of GSDMB expression on individuals with KIRC patients.

BAP1 inactivation promotes lactate production by leveraging the subcellular localization of LDHA in melanoma.

BRCA1-associated protein 1 (BAP1) acts as a tumor suppressor and can affect the cell cycle, tumor immunity, and cellular metabolism through multiple pathways. In melanoma, BAP1 mutations promote tumor cell glycolysis, leading to increased lactate production. The tumor microenvironment with high lactate levels is often associated with immunosuppression and tumor progression. The inhibitory effect of BAP1 on glycolysis has been found in a variety of tumors, but the specific mechanism by which BAP1 inhibits lactate production still needs to be elucidated. In this study, we show that BAP1 can interact directly with lactate dehydrogenase (LDHA), causing LDHA to accumulate in the nucleus. Conversely, BAP1 deletion leads to the accumulation of LDHA in the cytoplasm, catalyzing the production of lactate from pyruvate that results in increased lactate levels inside and outside the cell. By elucidating the interaction between BAP1 and LDHA and the subsequent effects on lactate production in melanoma cells, this work provides insights into the mechanism of BAP1-mediated metabolic regulation. Furthermore, it may provide novel directions for the clinical treatment of BAP1-mutant melanoma.

Targeting the JAK-STAT pathway in colorectal cancer: mechanisms, clinical implications, and therapeutic potential

Colorectal cancer (CRC) remains one of the most prevalent and fatal malignancies worldwide, consistently ranking among the top three in terms of incidence and mortality. Despite notable advancements in early detection and therapeutic interventions, survival outcomes for advanced-stage CRC are still dismal, largely due to issues such as drug resistance and metastasis. Recent research has increasingly implicated the JAK-STAT signaling pathway as a pivotal contributor to CRC pathogenesis. This evolutionarily conserved pathway plays a key role in transmitting extracellular signals to the nucleus, thereby modulating gene expression involved in numerous fundamental biological processes. In CRC, dysregulation of the JAK-STAT pathway is frequently observed and is strongly associated with tumor progression, including processes such as cellular proliferation, apoptosis, metastasis, immune evasion, and the sustenance of cancer stem cells. Given its integral role in CRC advancement, the JAK-STAT pathway has gained recognition as a viable therapeutic target. Extensive evidence from preclinical and clinical models supports the efficacy and safety of targeting components of the JAK-STAT pathway, presenting new therapeutic possibilities for patients with CRC, particularly in addressing drug resistance and enhancing treatment outcomes. This review offers a detailed exploration of the JAK-STAT pathway, focusing on its regulatory mechanisms in CRC-related malignancies. Moreover, it examines the association between JAK-STAT protein expression, clinical features, prognosis, and its therapeutic potential in CRC management.

Machine Learning Integration with Single-Cell Transcriptome Sequencing Datasets Reveals the Impact of Tumor-Associated Neutrophils on the Immune Microenvironment and Immunotherapy Outcomes in Gastric Cancer

The characteristics of neutrophils play a crucial role in defining the tumor inflammatory environment. However, the function of tumor-associated neutrophils (TANs) in tumor immunity and their response to immune checkpoint inhibitors (ICIs) remains incompletely understood. By analyzing single-cell RNA sequencing data from over 600,000 cells in gastric cancer (GSE163558 and GSE183904), colorectal cancer (GSE205506), and lung cancer (GSE207422), we identified neutrophil subsets in primary gastric cancer that are associated with the treatment response to ICIs. Specifically, we focused on neutrophils with high expression of CD44 (CD44_NEU), which are abundant during tumor progression and exert significant influence on the gastric cancer immune microenvironment. Machine learning analysis revealed 22 core genes associated with CD44_NEU, impacting inflammation, proliferation, migration, and oxidative stress. In addition, multiple immunofluorescence staining and gastric cancer spatial transcriptome data (GSE203612) showed a correlation between CD44_NEU and T-cell infiltration in gastric cancer tissues. A risk score model derived from seven essential genes (AQP9, BASP1, BCL2A1, PLEK, PDE4B, PROK2, and ACSL1) showed better predictive capability for patient survival compared to clinical features alone, and integrating these scores with clinical variables resulted in a prognostic nomogram. Overall, this study highlights the heterogeneity of TANs, particularly the CD44_NEU critical influence on immunotherapy outcomes, paving the way for personalized treatment strategies.

Methylation changes and INS-IGF2 expression predict progression in early-stage Wilms tumor.

Wilms tumor, the most common pediatric kidney cancer, accounts for 5% of childhood cancers and is classified by stage and histological subtype. Despite high survival rates (80-85%), approximately 15% of patients experience relapse, reducing survival to around 50%. Epigenetic changes, particularly DNA methylation, play a critical role in Wilms tumor pathogenesis. This study investigates the prognostic potential of DNA methylation in stage I and II patients with favorable histology, aiming to identify early relapse biomarkers. Genome-wide methylation was assessed using methylation microarrays in tumor tissues from relapsed patients (n = 9) and those with complete responses (n = 9), alongside normal tissues (n = 3 each). Differentially methylated probes and regions were analyzed, with additional ROC and survival analyses. Real-time PCR was used to measure IGF2 and INS-IGF2 gene expression. The analysis revealed hypomethylation in intergenic regions in remission patients, identifying 14 differentially methylated positions as potential biomarkers. Increased INS-IGF2 expression was associated with relapse, suggesting its role in disease progression. While the study concentrated on stages I and II patients, where relapse rates are lower, this focus inherently led to a smaller sample size. Despite this, the findings provide valuable insights into the potential role of DNA methylation markers for monitoring disease progression and guiding personalized treatment in Wilms tumor patients.

Mathematical model of tumor immune microenvironment with application to the combined therapy targeting the PD-1/PD-L1 pathway and IL-10 cytokine antibody.

The tumor microenvironment constitutes a complex system shaped by the intricate interactions among tumor cells, immune cells, and cytokines. Within this environment, the interplay between immune cells and cytokines is crucial in influencing tumor growth and progression. Despite advancements in clinical tumor immunotherapy, there remains a gap in comprehensive simulations of tumor immune responses, particularly regarding cytokine-driven processes. This study aims toaddress this gap by investigating the regulatory interactions among tumor cells, immune cells, and cytokines to simulate the complexities of tumor immunotherapy. We develop a comprehensive modeling and computational framework incorporating PD-1 inhibitors and interleukin-10 (IL-10) antibodies. Through detailed mathematical analysis, we elucidate the impact of changes in the immune microenvironment on tumor cellsnumber. Our findings highlight the significant therapeutic effect of anti-PD-1 and IL-10 inhibitors, with increased drug dosage correlating with a reduction in tumor burden. Furthermore, combination therapy demonstrates a marked extension of survival with reduced dosages compared to monotherapy. Based on model simulations, we proposed prognostic predictions by assessing the microenvironmental status before treatment. The findings indicate a promising method forenhancing treatment effectiveness and offering potentialadvantages to patients receiving tumor immunotherapy.

Fungal Influences on Cancer Initiation, Progression, and Response to Treatment.

Fungal dysbiosis is increasingly recognized as a key factor in cancer, influencing tumor initiation, progression, and treatment outcomes. This review explores the role of fungi in carcinogenesis, with a focus on mechanisms such as immunomodulation, inflammation induction, tumor microenvironment remodeling, and interkingdom interactions. Fungal metabolites are involved in oncogenesis, and antifungals can interact with anticancer drug, including eliciting potential adverse effects and influencing immune responses. Furthermore, mycobiota profiles have potential as diagnostic and prognostic biomarkers, emphasizing their clinical relevance. The interplay between fungi and cancer therapies can impact drug resistance, therapeutic efficacy, and risk of invasive fungal infections associated with targeted therapies. Finally, emerging strategies for modulating mycobiota in cancer care are promising approaches to improve patient outcomes.

Long non-coding RNA H19 as a prognostic biomarker for oral squamous cell carcinoma

BackgroundH19, a 2.3 kb lncRNA, has been linked to tumor metastasis and progression, but its significance in oral squamous cell carcinoma (OSCC) remains unclear. H19 was initially thought to have a tumor-suppressive function, but recent studies have shown that it possesses both tumor-promoting and suppressive functions. The variation in H19 expression may be due to the influence of tobacco or low basal expression levels. However, there are limited studies available on the association between H19 and its role in the prognosis of OSCC.ObjectiveThe present study analyzes the expression of H19 correlated with clinicopathological parameters, tobacco habit, loco-regional recurrence, and overall survival.MethodsA longitudinal study was undertaken using 96 formalin-fixed paraffin-embedded (FFPE) OSCC tissues and 30 FFPE adjacent normal mucosa (NM) tissues from patients who had surgery between 2015 and 2018. The tissues were subjected to quantitative reverse-transcription PCR (qRT-PCR) to determine H19 expression. The differential expression levels of H19 in OSCC were compared to clinicopathological variables and risk habits using the t-test and ANOVA. H19 expression correlated overall survival was analyzed by drawing the Kaplan–Meier curve followed by the log-rank test. A multivariate Cox proportional hazards regression analysis was performed to determine the ability of H19 to independently predict loco-regional recurrence and overall survival for OSCC.ResultH19 was significantly underexpressed in OSCC compared to NM in both the study cases and the TCGA OSCC database. The lower expression of H19 was significantly associated with the tobacco smoking habit and was not associated with any clinical or pathological features. Multivariate Cox’s proportional hazards regression analysis indicated that low H19 expression and positive lymph node metastasis were independent predictors of overall survival for OSCC. Higher age, higher TNM staging, and low H19 expression were independent predictors of loco-regional recurrence.ConclusionThe findings in the present study indicate that H19 is a novel prognostic marker and may provide a therapeutic strategy for the targeted treatment of OSCC, and tobacco may play a role in the expression of H19.

TMEM35B as a novel biomarker for diagnosing gliomas.

There is little information about transmembrane protein 35B (TMEM35B) expression in glioma, and its functions in glioma remains no clue. Immunohistochemistry was used to measure TMEM35B expression levels and CCK8 and Transwell assays were analyzed the proliferative and migratory and invasive. TMEM35B protein was significantly higher in gliomas and correlated with a higher tumor TNM stages. Receiver operating characteristic curve analysis revealed that TMEM35B had high diagnostic value in distinguishing among glioma, normal tissues, tumor stages III+IV, and I+II. Additionally, TMEM35B knockdown inhibited the proliferative, migratory, and invasive capacities of glioma cells. TMEM35B expression is upregulated in gliomas, and its knockdown hinders tumor progression, highlighting the protein as a potential biomarker for glioma diagnosis.