Melanoma is the most dangerous type of skin cancer. Although it accounts for only about 1% of all skin cancer cases, it is responsible for the majority of skin cancer-related deaths. Early detection and accurate diagnosis are crucial for improving the prognosis and survival rates of patients with melanoma. This paper presents a novel approach for the automatic identification of cutaneous lesions by integrating convolutional neural networks (CNNs) with long short-term memory (LSTM) networks. In the proposed approach, the image of each skin lesion is divided into a sequence of tags of a particular size, which is then treated by the LSTM network to capture temporal dependence and relevant relationships between different spatial regions. This patching sequence allows the modeling system to analyze the local pattern in the image. Time CNN layers are later used to extract spatial functions, such as texture, edges, and color variation, on each patch. A Softmax layer is then used for classification, providing a probability distribution over the possible classes. We use the HAM10000 dataset, which contains 10,015 skin lesion images. Experimental results demonstrate that the proposed method outperforms recent models in several metrics, including accuracy, recall, precision, F1 score, and ROC curve performance.

Non-small-cell lung cancer (NSCLC) is the most common type of lung cancer. This study aimed to investigate the mechanism of vir-like m6A methyltransferase-associated protein (VIRMA, also called KIAA1429) in NSCLC cell proliferation. Levels of KIAA1429, long-chain non-coding RNAs translation regulatory long non-coding RNA 1 (lncRNA TRERNA1), and homeobox A6 (HOXA6) were measured in NSCLC cells and normal cells. The enrichment of KIAA1429 and m6A on lncRNA TRERNA1 was detected. LncRNA TRERNA1 stability and subcellular localization of lncRNA TRERNA1 were detected. The binding of EZH2 to lncRNA TRERNA1 was analyzed. The enrichment of EZH2 and H3K27me3 on the HOXA6 promoter was analyzed. The mechanism of KIAA1429 was validated in vivo. KIAA1429 and lncRNA TRERNA1 were overexpressed in NSCLC cells and HOXA6 was downregulated. Knockdown of KIAA1429 significantly reduced NSCLC cell proliferation. KIAA1429 enhanced lncRNA TRERNA1 RNA stability via m6A modification and upregulated lncRNA TRERNA1 expression, which recruited EZH2 and increased H3K27me3 modification in the HOXA6 promoter region, thus suppressing HOXA6 expression. LncRNA TRERNA1 overexpression or HOXA6 downregulation alleviated the inhibitory effect of KIAA1429 downregulation on NSCLC cell proliferation. KIAA1429 downregulation inhibited NSCLC cell proliferation in vivo. In conclusion, KIAA1429 promotes NSCLC proliferation through the TRERNA1/HOXA6 axis.

NSUN6 is a regulator of tRNA methylation that partially exists in the Golgi and centrosomes. It catalyzes the methylation of tRNACys and tRNAThr at the C72 site, which affects tRNA generation. However, its expression, prognosis, and immune invasion in pan-cancer have not been studied. This extensive research tapped into the TCGA database, gathering 33 carefully paired sets of cancer and nearby normal tissues, covering a broad spectrum of 33 different cancer types. Moreover, this study explored how NSUN6 expression relates to the presence of immune and stromal cells in the tumor's intricate immune environment. To further understand NSUN6's role, a detailed Gene Set Enrichment Analysis (GSEA) was conducted, revealing its enrichment patterns in various carcinoma subtypes and hinting at its involvement in tumor growth. Analysis of NSUN6 expression patterns revealed a significant increase in eight cancer types, including lung adenocarcinoma and pancreatic cancer (P < 0.001). Additionally, a reduction was observed in six cancer types, such as cholangiocarcinoma and thyroid cancer (P < 0.001). Survival analysis indicated that individuals with lung adenocarcinoma, pancreatic cancer, and other cancers expressing high levels of NSUN6 had improved prognosis. The association between NSUN6 expression and patient outcomes was evident, including overall survival, disease-specific survival, disease-free interval, and progression-free interval. Furthermore, individuals with high levels of NSUN6 expression showed significantly longer survival times than those with low levels (P < 0.05). The involvement of NSUN6 in immune infiltration was evident, GSEA showed a significant correlation between NSUN6 expression and the five most significant enrichment pathways in different tumors. The NSUN6 gene functions as an initial indicator for diagnosis in renal clear cell carcinoma, pancreatic cancer, lung adenocarcinoma, and low-grade brain glioma. There is an association between its elevated expression and the predictive outcome, as well as the immune system's infiltration, in 33 varieties of cancer. This study is limited by its reliance on in silico analyses without experimental validation. Additionally, the use of publicly available datasets may introduce variability due to differences in data sources and platforms.

Lung cancer ranks as the primary contributor to cancer-related fatalities on a global scale, hallmarked by a poor prognosis. Programmed cell death (PCD) is critically involved in regulating the onset, progression, and treatment of lung adenocarcinoma (LUAD). Existing prognostic models concerning PCD focus solely on individual mechanisms and fail to account for the intricate interaction among multiple regulatory mechanisms. In this study, the LUAD samples were sorted into low immune cell invasion subtype (C1) and high immune cell invasion subtype (C2) by clustering analysis. A PCD prognostic signature model was developed by LASSO Cox regression analysis. Tumors in the high-risk group were categorized as "cold" and characterized by immunosuppression, which was linked to an unfavorable prognosis and sensitivity to drug therapy. However, the opposite was true for the low-risk group, which was associated with a favorable prognosis and sensitivity to immunotherapy. Single-cell analysis found that the PCD signature model could activate several immune cells, thereby affecting the tumor microenvironment (TME) of LUAD. Furthermore, ENO1, could be used as a target for LUAD prognosis and immunotherapy. This study aims to comprehensively explore the functional mechanisms of various PCD regulatory patterns in LUAD to provide accurate prognosis and personalized treatment plans.

This study aims to elucidate the functional mechanisms of LncRNA DRAIC in renal cell carcinoma, particularly its regulation of tumor progression via microRNA-145-3p and ABRACL. The downstream targets of LncRNA DRAIC were predicted using databases, and their interactions with microRNA-145-3p were experimentally validated. The effects of LncRNA DRAIC overexpression on the proliferation, invasion, and migration of renal carcinoma cells were evaluated using stable cell lines, CCK-8 assays, Transwell assays, subcutaneous tumor transplantation in nude mice, and in vivo fluorescence imaging experiments. Techniques such as Western blot and RT-PCR were utilized to monitor the expression levels of ABRACL under the regulation of LncRNA DRAIC, further confirming its role in renal carcinoma cell functions. Overexpression of LncRNA DRAIC significantly enhanced the proliferation, invasion, and migration capabilities of renal carcinoma cells. Moreover, it was discovered that LncRNA DRAIC regulates the expression of ABRACL by modulating microRNA-145-3p, thereby affecting the functionality of renal carcinoma cells. This reveals the critical mechanisms of LncRNA DRAIC in renal cell carcinoma, where it governs tumor cell biology through microRNA-145-3p and ABRACL, offering new targets and theoretical foundations for the treatment of renal cell carcinoma.

There are complex associations between the imaging phenotype and underlying histopathology of hepatocellular carcinomas (HCC). The recently proposed SMARS score (acronym comprising Shape of tumour, Mosaic architecture, AFP level, Rim APHE, and Satellite lesion) could discriminate proliferative and non-proliferative HCC tumours in a non-invasive way and was associated with treatment outcomes. However, a systematic validation of this score is needed and it is unclear whether associations with histopathology features exist. The present study elucidates possible correlations between the SMARS score defined by CT and MRI images with immunohistochemistry features of the pathological specimens in a curatively treated HCC cohort. A total of 44 patients (mean age: 59.6 ± 10.7 years) with histologically confirmed HCC, who underwent curative surgical resection, were included in the present analysis. Contrast enhanced MRI and CT images were performed before surgery and the SMARS score was calculated. The pathological specimens were analyzed for programmed death ligand 1 (PD-L1), Glypican-3, CD3-tumour infiltrating lymphocyte, CD68 positive cells, CD34 positive microvessel density (MVD). The median SMARS score derived from MRI images was 1.4 (interquartile range: -0.32; 2.18) and from CT images it was - 0.32 (interquartile range: -1.08; 0.56). According to the proposed threshold, 29 tumours were categorized as proliferative HCC (82.9%) and six tumours as nonproliferative HCC (17.1%) accordingly to the MRI SMARS score. According to the CT SMARS score 24 tumours were categorized as proliferative HCC (61.5%) and 15 as nonproliferative HCC (38.5%). The SMARS score derived from MRI images showed no correlations with the PD-L1, CD68, CD3 and MVD parameters. However, a moderate association was shown between the SMARS score with the Glypican-3 expression (r = 0.37, p = 0.03). The SMARS score derived from CT images, instead, showed correlations with two of the PD-L1 parameters (for PD-L1 tumour positive score r=-0.37, p = 0.02 and for PD-L1 combined positive score r=-0.35, p = 0.03) while no other association with the remaining parameters was detected. The SMARS score as a promising novel imaging score is associated with the Glypican-3 and PD-L1 expression in curatively treated HCC patients. Differences between the CT and MRI defined score needs to be investigated in further trials on larger patient cohorts.

Protein kinase R (PKR) functions both as a promoter and inhibitor in various cancers; however, its role in pancreatic ductal adenocarcinoma (PDAC) remains unclear. We investigated the role of PKR in PDAC. PKR expression in PDAC cell lines was assessed using real-time reverse transcriptase polymerase chain reaction and western blotting. The effect of PKR on cell proliferation was examined using MTS assay. To determine the mechanisms of PKR's action on PDAC, RNA-sequencing analysis was performed, and the effects of PKR knockdown on cell cycle progression and apoptosis in PDAC cells were examined using flow cytometry. PDAC cell lines transfected with PKR-targeting short interfering RNAs or treated with PKR inhibitors exhibited significantly reduced proliferation. RNA-sequencing analysis revealed substantial upregulation of GADD45A expression upon inhibition of PKR expression. Following PKR silencing, cell cycle analysis showed marked accumulation of cells in G1 phase, consistent with the role of GADD45A as a cell cycle regulator. Proliferation inhibition caused by PKR knockdown was reversed by downregulation of GADD45A, suggesting that PKR and GADD45A interact to regulate PDAC cell growth. PKR promotes PDAC cell proliferation by modulating the cell cycle via regulation of GADD45A expression, demonstrating its potential as a therapeutic target for PDAC.

The Nuclear Factor of Activated T-cells cytoplasmic 1 (NFATc1) is identified to be an oncogene in several human cancers. However, its specific role in HCC progression and the relevant mechanisms remain unclear. To investigate this, we analyzed NFATc1 expression in clinical HCC samples (n = 289) using RT-qPCR, Western blotting, and immunohistochemistry (IHC). In vitro assays assessed HCC cell proliferation, migration, invasion, apoptosis, and cell cycle, while in vivo studies using BALB/c nude mice evaluated the effects of NFATc1 on HCC growth and metastasis. Mechanistic studies were conducted to explore NFATc1's downstream signaling pathways. Results revealed that NFATc1 is significantly upregulated in HCC tissues compared to adjacent non-cancerous tissues, correlating with poor prognosis. Overexpression of NFATc1 enhanced HCC cell proliferation, migration, and invasion both in vitro and in vivo, while silencing NFATc1 reduced these malignant traits. Mechanistic analysis indicated that NFATc1 activation correlates with NF-κB/TMP21 signaling and senescence-associated secretory phenotype (SASP) amplification, independent of growth arrest. These findings suggest that NFATc1 plays a pivotal role in HCC progression, potentially through the modulation of SASP activation. Targeting NFATc1 and its signaling pathways could be a promising therapeutic approach for HCC.

Colorectal cancer (CRC) is one of the most common malignant tumors with high incidence and mortality. The challenge remains to construct reliable prognostic prediction models and to further elucidate the key molecular mechanisms of tumor progression. To address this, we performed WGCNA based on 120 immune cell expression profiles from GEO sources to obtain a collection of monocytes/macrophages-related genes. The prognostic model was constructed by univariate survival analysis and LASSO regression analysis. Then, the prognostic model was validated by Multivariate Cox regression, Kaplan-Meier survival analysis and ROC analysis. In this prognostic model, we identified that PLIN2 has a potential value for CRC prognosis. PLIN2 expression in monocytes/macrophages was verified by scRNA-seq datasets and spatial transcriptome datasets, and PLIN2 was found to promote macrophage transformation to M2 subtype. Clinical specimens and tissue microarrays confirmed the differential expression and prognostic value of PLIN2 in CRC patients. Functional experiments demonstrated that PLIN2 gene overexpression promoted the proliferation, migration and invasion of CRC cells and significantly facilitated tumor growth in vivo. Mechanistically, we revealed that CD36 is a potential downstream target gene of PLIN2. The CD36 inhibitor Sulfo-N-succinimidyl Oleate significantly reversed PLIN2-induced proliferation, migration, invasion, and EMT activity of CRC cells in vitro and in vivo. Immunoprecipitation and immunofluorescence experiments confirmed that PLIN2 could interact with CD36. PLIN2 stabilized CD36 protein expression by inhibiting the proteasomal degradation pathway, thereby promoting CD36-mediated EMT activity. Overall, our study highlights that the PLIN2/CD36 axis regulates EMT activity and CRC progression, suggesting that interventions in this signaling pathway may offer a promising therapeutic approach to CRC progression. Schematic diagram elucidating the role of PLIN2 in CRC by Figdraw. FA is transported into the cell via CD36-mediated endocytosis. In CRC cells, PLIN2 promotes stability of CD36 and interacts with CD36 to activate the EMT process. However, the CD36 inhibitor SSO inhibits the binding of FAs to CD36 and attenuates its endocytosis, thereby reversing the PLIN2-mediated EMT process. Ultimately, the PLIN2-induced enhancement of CRC cell proliferation, migration, and invasion is attenuated by the CD36 inhibitor SSO.

Biomarker-enriched, chemotherapy-free treatments for patients with advanced gastric and gastroesophageal junction cancer have not been widely explored. In this multicenter, phase 2 trial (NCT04363801), we evaluated the efficacy and safety of second-line doublet immunotherapy, combining DKN-01, an immunomodulating antibody targeting Dickkopf-related protein 1 (DKK1), with the anti-programmed cell death-1 (PD1) antibody, tislelizumab in patients with advanced gastric/gastroesophageal junction cancer and elevated tumor DKK1 expression, a putative predictive biomarker for DKN-01. Here we report part B (second line cohort) of the larger DisTinGuish trial. The primary endpoint was safety and tolerability, with secondary endpoints including objective response rate (ORR), overall survival (OS), progression free survival (PFS), and disease control rate (DCR). The trial met the prespecified primary endpoint. In the safety population (n = 52), 21 (40.4%) patients reported at least 1 DKN-01-related adverse event, most of which were low-grade, with fatigue (15.4%) and nausea (9.6%) being most common. The ORR was 21.7% in the overall population (n = 46) and 31.8% in the programmed death-ligand 1 (PD-L1) ≥ 5% population. The median OS was 8.2 months, median PFS 1.4 months, and DCR rate 34.8% in the overall population. Although exploratory, the results of this trial compare favorably against second-line benchmarks of Keynote-061 and RAINBOW and support the safety and tolerability of DKN-01 combined with tislelizumab.

Oligometastasis represents a transitional state between early localized disease and widespread metastasis, characterized by limited tumor burden and distinct tumor biological behavior. Due to the relatively restricted number of metastatic lesions and involved organs, aggressive systemic therapy combined with local consolidative therapy offers potential for cure. With rapid advancements in molecular targeted therapies and immunotherapy, comprehensive management of oligometastatic non-small cell lung cancer (NSCLC) has gained increasing attention. This review summarizes the definition of NSCLC oligometastasis, recent therapeutic progress, and existing challenges, aiming to provide insights for clinical diagnosis and treatment strategies.
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Primary pulmonary mucoepidermoid carcinoma (PMEC) is an exceedingly rare malignancy originating from bronchial submucosal glands, accounting for <0.2% of lung cancers. Histologically characterized by a triphasic composition of mucinous, epidermoid, and intermediate cells, PMEC is classified into low-grade (favorable prognosis) and high-grade (aggressive behavior) subtypes. This study aimed to investigate the clinicopathological characteristics and prognostic indicators of PMEC.

Neoadjuvant immunochemotherapy has emerged as an indispensable therapeutic modality for non-small cell lung cancer (NSCLC). However, its clinical application experience remains limited, and the associations between various clinical factors and treatment benefits remain undefined. This study aims to evaluate the efficacy and safety of neoadjuvant immunochemotherapy in patients with stage IB-IIIB NSCLC in a real-world setting, analyze survival outcomes among subgroups with diverse clinical characteristics, and identify potential clinical predictive factors for pathological response.

Gut microbiota modulation is an emerging strategy to improve cancer therapy outcomes. This study evaluated the safety and therapeutic potential of combining oral vancomycin-a non-absorbed, gut-restricted antibiotic with primary activity against gram-positive bacteria-with stereotactic body radiotherapy (SBRT) in early-stage non-small cell lung cancer (NSCLC). The underlying hypothesis was that vancomycin-induced changes in gut microbiota could enhance the antitumor effects of SBRT.

Neoadjuvant immune checkpoint blockade (nICB) has revolutionized cancer treatment, yet the underlying mechanisms of resistance in bladder cancer remain to be explored.

Spatial transcriptomics (ST) encompasses rich multi-modal information related to cell state and organization. Precisely identifying spatial domains with consistent gene expression patterns and histological features is a critical task in ST analysis, which requires comprehensive integration of multi-modal information. Here, we propose TriCLFF, a contrastive learning-based multi-modal feature fusion framework, to effectively integrate spatial associations, gene expression levels, and histological features in a unified manner. Leveraging an advanced feature fusion mechanism, our proposed TriCLFF framework outperforms existing state-of-the-art methods in terms of accuracy and robustness across four datasets (mouse brain anterior, mouse olfactory bulb, human dorsolateral prefrontal cortex, and human breast cancer) from different platforms (10x Visium and Stereo-seq) for spatial domain identification. TriCLFF also facilitates the identification of finer-grained structures in breast cancer tissues and detects previously unknown gene expression patterns in the human dorsolateral prefrontal cortex, providing novel insights for understanding tissue functions. Overall, TriCLFF establishes an effective paradigm for integrating spatial multi-modal data, demonstrating its potential for advancing ST research. The source code of TriCLFF is available online at https://github.com/HBZZ168/TriCLFF.

Data on long-term outcomes for men with prostate cancer treated according to current guidelines are limited. We aimed to estimate the long-term risk of death from prostate cancer and other causes in men with nonmetastatic prostate cancer who received primary treatment according to current guidelines.

The NCCN Guidelines for Thyroid Carcinoma address the management of different types of thyroid carcinoma, including papillary, follicular, oncocytic, medullary, and anaplastic carcinoma. The NCCN Thyroid Carcinoma Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights focus on the panel's most recent recommendations regarding systemic therapies for thyroid carcinoma as well as the supporting clinical data.

The role of the lung microbiota in cancer remains unclear. Here, we reveal that Staphylococcus is selectively enriched in metastatic tumor lesions and is associated with tumor recurrence in lung cancer patients. Using patient-derived bacterial strains, we employ a combination of cell line, organoid, mouse allograft, and xenograft models to demonstrate that S. nepalensis and S. capitis promote the metastatic potential of lung cancer cells. Mechanistically, lactate secreted by S. nepalensis and S. capitis upregulates MCT1 expression in tumor cells, facilitating lactate uptake and activating pseudohypoxia signaling. These effects can be eliminated by knocking out the lactate-producing genes (D-lactate dehydrogenase [ddh]/L-lactate dehydrogenase [ldh]) in the bacterial strains. Furthermore, we show that inhibiting MCT1 attenuates Staphylococcus-induced tumor metastasis both in vitro and in vivo. Collectively, our results demonstrate that tumor-resident Staphylococcus species promote lung cancer metastasis by activating host pseudohypoxia signaling and further identify key regulators as potential targets for therapeutic development.

We aimed to assess the frequency of systemic anti-cancer therapy (SACT) use in patients with advanced non-small cell lung cancer (NSCLC), comparing Māori and non-Māori. Secondary aims were to assess predictive factors for patients managed with SACT, SACT agent regimens and lung cancer-specific mortality.