Relapsed/Refractory (R/R) diffuse large B-cell lymphoma (DLBCL) represents a subgroup with a high incidence and dismal prognosis. Currently, there is a lack of robust models for predicting R/R DLBCL. Therefore, we conducted a retrospective study to identify key determinants to be incorporated into a novel nomogram to enhance the identification of DLBCL patients at elevated risk of refractoriness/recurrence.

We included 293 newly-diagnosed DLBCL patients from Harbin Medical University Cancer Hospital, collected from 2008-2017. Patients were randomly divided into a training cohort (n = 206) and a validation cohort (n = 87) at a 7:3 ratio. The training cohort underwent univariable analysis to select variables for a binary logistic regression model. These variables were also prioritized using a random forest algorithm. The developed nomogram was evaluated with the receiver-operator characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) for its clinical utility.

Univariable analysis pinpointed several factors significantly associated with refractoriness/recurrence, including pathological subtype, lactate dehydrogenase (LDH), International Prognostic Index (IPI), treatment, absolute lymphocyte count (ALC), lymphocyte/monocyte ratio (LMR), and prognostic nutritional index (PNI). Binary logistic regression highlighted pathological subtype, LDH, treatment, and ALC as key predictors, which were incorporated into the nomogram. The nomogram showed excellent calibration and accuracy in both cohorts, and comparative DCA and ROC analysis demonstrated its superior net benefit and area under the curve (AUC) compared to traditional indexes like IPI, R-IPI, and NCCN-IPI.

This nomogram serves as a valuable tool for predicting the likelihood of refractoriness or recurrence in DLBCL patients.

Recent studies on head and neck squamous cell carcinoma (HNSCC) tumorigenesis have revealed several dysregulated molecular pathways. The phosphatidylinositol-3-kinase (PI3K) signaling pathway is frequently activated in HNSCC, making it an attractive target for therapies. PHT-427 is a dual inhibitor of PI3K and the mammalian target of AKT/PDK1. This study evaluates the anticancer efficacy of the inhibitor PHT-427 loaded into polymeric nanoparticles (NP) based on α-TOS (NP-427) administered by intratumoral injection into a hypopharyngeal squamous cell carcinoma (FaDu cells) heterotopic xenograft mouse model. The nanocarrier system, based on block copolymers of N-vinylpyrrolidone (VP) and a methacrylic derivative of α-TOS (MTOS), was synthesized, and PHT-427 was loaded into the delivery system. First, we evaluated the effect of NP-427 on tumor growth by measuring tumor volume, mouse weight, survival, and the development of tumor ulceration and necrosis. In addition, we measured PI3KCA/AKT/PDK1 gene expression, PI3KCA/AKT/PDK1 protein levels, Epidermal Growth Factor Receptor (EGFR), and angiogenesis in the tumor tissue. PHT-427 encapsulation increased drug efficacy and safety, as demonstrated by decreased tumor volume, reduced PI3K/AKT/PDK1 pathway expression, and improved antitumor activity and necrosis induction in the mouse xenograft model. EGFR and angiogenesis marker (Factor VIII) expression were significantly lower in the NP-427 group compared to other experimental groups. Administration of encapsulated PHT-427 at the tumor sites proves promising for HNSCC therapy.

Depressive symptoms are prevalent among parents of children with cancer, significantly impacting their well-being. Problem-solving skills, strongly linked to depressive symptoms, offer a promising avenue for intervention. This study aimed to identify latent profiles of parental problem-solving skills and evaluate differences in depressive symptoms across these profiles.

A cross-sectional survey was conducted with 318 parents of children with cancer in mainland China. Self-reported data on demographics, problem-solving skills, and depressive symptoms were collected. Latent profile analysis was used to classify parental problem-solving skills into distinct profiles, and multiple logistic regression identified predictors of profile membership.

Three profiles of problem-solving skills were identified: (1) problem-oriented and constructive (n ​= ​94, 29.6%), (2) impulsivity-oriented and irrational (n ​= ​76, 23.9%), and (3) emotion-oriented and avoidant (n ​= ​148, 46.5%). Parents with higher education, greater income, and urban residency were more likely to belong to the problem-oriented group. Fathers predominated in the impulsivity-oriented group, while mothers were more represented in the emotion-oriented group. Significant differences in depressive symptoms were observed across profiles, with the problem-oriented group reporting the lowest levels.

This study highlights the heterogeneity of problem-solving skills among parents of children with cancer and underscores the need for tailored interventions. Addressing specific characteristics of each profile can improve parental well-being and provide targeted support for this vulnerable population.

ChiCTR2300071828.

Phototherapy is a treatment method that uses the characteristics of different bands of light to treat diseases. Tumor immunotherapy, on the other hand, treats tumors by regulating the body's immune system. The combination of phototherapy and immunotherapy can significantly enhance the treatment of melanoma. In this study, we prepared and characterized INEs, a novel ethosome composed of the photosensitizer IR251 and the Indoleamine-2, 3-dioxygenase (IDO) inhibitor NLG919. INEs demonstrated excellent phototherapeutic properties, strong phototoxicity, and a notable ability to inhibit IDO. Under 808 nm laser irradiation, INEs effectively induced immunogenic cell death (ICD) in melanoma cells. In vivo experiments demonstrated that INEs injection into primary tumors triggered ICD, promoted maturation of DC cells, and activated naive T cells, leading to the production of effector T cells (specifically CD4+ and CD8+ T cells) that targeted and killed tumor cells. Both primary and distant tumors were treated simultaneously with favorable biosafety. In conclusion, INEs represent a promising strategy for melanoma treatment by a combination of phototherapy and immunotherapy with high safety. This study provides new insights and a theoretical basis for the clinical treatment of melanoma.

Follistatin-like 3 (FSTL3) is a glycoprotein known to promote tumor growth, invasion, and angiogenesis in various cancers. However, its role in Colorectal Cancer (CRC), particularly concerning the hypoxia-inducible factor 1α (HIF1α) signaling pathway, remains unclear. The HIF1α pathway is critical in CRC progression, enabling tumor cells to adapt to hypoxia through angiogenesis, Epithelial-Mesenchymal Transition (EMT), and metabolic reprogramming. Analysis of The Cancer Genome Atlas (TCGA) and GSE39582 datasets revealed that FSTL3 is significantly upregulated in CRC tissues and correlates with poor Overall Survival (OS), Progression-Free Survival (PFS), and aggressive features such as venous, lymphatic, and perineural invasion. In vitro experiments demonstrated that FSTL3 overexpression in HCT15 and HCT116 cells promoted proliferation, migration, and cell cycle progression, whereas knockdown in LOVO and Caco2 cells suppressed these processes and induced apoptosis. Transcriptome sequencing and western blot analysis indicated that FSTL3 activated the HIF1α pathway by upregulating HIF1α, ANGPT2, and HK3, which are key regulators of angiogenesis and glycolysis. Importantly, treatment with the HIF1α inhibitor KC7F2 reversed the oncogenic effects of FSTL3 overexpression both in vitro and in vivo. In xenograft and tail vein metastasis models, KC7F2 suppressed tumor growth, reduced pulmonary metastasis, and restored lung tissue integrity, further downregulating FSTL3 and HIF1α expression. These findings suggest that FSTL3 promotes CRC progression via the HIF1α pathway and highlight its potential as a prognostic biomarker and therapeutic target for CRC treatment.

Non-coding RNAs (ncRNAs) are frequently dysregulated in various cancers and have been implicated in the etiology and progression of cancer. Ovarian cancer, the most fatal gynecological cancer, has a poor prognosis and a high patient fatality rate due to metastases. In this study, we classified patients with ovarian cancer into three groups based on their ncRNA expression levels. Notably, an ncRNA transcribed by RNA polymerase III, RNA component of mitochondrial RNA processing endoribonuclease (RMRP), is highly expressed in a group with a poor prognosis. Functional assays using SKOV3 and HeyA8 human ovarian cancer cell lines revealed that while RMRP modulation had no significant effect on cell viability, it markedly enhanced cell invasion. Knockdown and ectopic expression experiments demonstrated that RMRP promotes the secretion of matrix metalloproteinase (MMP)-2 and -9, thereby facilitating ovarian cancer cell invasiveness. Transcriptomic analysis further revealed a positive correlation between RMRP expression and genes involved in cellular localization, including RAB31, a member of the Ras-related protein family. Notably, RAB31 knockdown abrogated the pro-invasive effects of RMRP, identifying it as a key downstream effector in SKOV3 and HeyA8 cells. In addition, MechRNA analysis identified RAB31 as a putative RMRP-interacting transcript. These findings establish RMRP as a critical regulator of RAB31-dependent MMP secretion and ovarian cancer cell invasion. Moreover, our results suggest that RMRP could serve as a promising prognostic biomarker for ovarian cancer.

Among cancer patients, those in advanced stages generally face higher mortality rates, highlighting the importance of early diagnosis in improving cure rates and survival outcomes. Compared to normal cells, tumor cells exhibit a lower polarity in their microenvironment, providing a promising avenue for early cancer detection. It is feasible to distinguish tumor cells from normal cells by leveraging the fluorescence response of probes to polarity. In this study, we designed a fluorescence probe, PCC, with high sensitivity to polarity for early cancer diagnosis. The probe demonstrated a remarkable fluorescence intensity increase of 100-fold in a low-polarity solvent (1,4-dioxane) compared to a high-polarity solvent (water). Additionally, PCC exhibited excellent tumor-targeting ability, large Stokes shift, strong anti-interference capability, and high photostability. When applied to tumor cells (HeLa and CT26、SGC-7901) and normal cells (RAW 264.7、HUVEC、L-02), the probe produced a fluorescence intensity difference exceeding fourfold. These findings indicate that PCC, as a polarity-sensitive fluorescence probe, holds significant promise for early cancer diagnosis.

To enhance immunotherapy efficacy in pancreatic cancer, it is crucial to characterize its immune landscape and identify key factors driving immune alterations. To achieve this, we quantitatively analyzed the immune microenvironment using multiplex immunohistochemistry, assessing the spatial relationships between immune and tumor cells to correlate with patient survival rates and oncological factors. Additionally, through Whole Exome Sequencing analysis based on public data, we explored genetic mutations that could drive these compositions. Finally, we validated T cell (Tc) migration mechanisms using patient-derived tumor organoids with induced KRAS mutation subtypes. Through this approach, we obtained the following meaningful results. First, immune cells in pancreatic cancer are denser in stromal regions than near tumor cells, with higher Tc distribution linked to increased patient survival rates. Second, the distance between tumor and Tc was within 100 μm, with higher Tc density found within 15-30 μm of the tumor cells. Third, while increasing CAF levels correspond to higher Tc density, higher ECM density tends to decrease Tc presence. Fourth, compared to KRAS G12D, KRAS G12V mutation increases various immune cells, notably Tc, which is closely linked to a dramatic rise in vascular cells. Finally, Tc migration was enhanced in tumor organoids with the G12V mutation, attributed to a reduction in the secretion of immunosuppressive cytokines. Our results indicate that KRAS mutation subtypes influence immune cell composition and function in the pancreatic cancer microenvironment, leading to varied immunotherapy responses. This underscores the need for personalized immune therapeutics and research models specific to KRAS mutations.

Breast cancer is a fatal malignancy facing human health, with most patients experiencing recurrence and resistance to chemotherapy. The immunosuppressive tumor microenvironment (TME) greatly limits the actual outcome of immunotherapy. This study aimed to develop a modality of theranostics nanoparticles for breast cancer based on a near-infrared light-triggered nanoparticle for the targeted delivery of ginsenoside Rg3 and immune adjuvants imiquimod (R837) for effective breast cancer immunotherapy. Folate-receptor (FA) targeting IR780-R837/ginsenoside Rg3-perfluorohexane (PFH) @ polyethylene glycol (PEG)-poly (lactide-co-glycolic acid) (PLGA) nanoparticles (FA-NPs) can be activated by near-infrared laser irradiation in tumors, which leads to rapid release of ginsenoside Rg3 and R837 in the regions with high expression of folate receptors and glucose transporter 1 (GLUT1). Meanwhile, the nanoparticles can be used as dual-mode contrast agents for photoacoustic and ultrasound imaging. This strategy provides a strong immune memory effect, which can prevent tumor recurrence after eliminating the initial tumor.

The development of deep learning algorithms has transformed medical image analysis, especially in brain tumor recognition. This research introduces a robust automatic microbrain tumor identification method utilizing the VGG16 deep learning model. Microscopy magnetic resonance imaging (MMRI) scans extract detailed features, providing multi-modal insights. VGG16, known for its depth and high performance, is utilized for this purpose. The study demonstrates the model's potential for precise and effective diagnosis by examining how well it can differentiate between areas of normal brain tissue and cancerous regions, leveraging both MRI and microscopy data. We describe in full the pre-processing actions taken to improve the quality of input data and maximize model efficiency. A carefully selected dataset, incorporating diverse tumor sizes and types from both microscopy and MRI sources, is used during the training phase to ensure representativeness. The proposed modified VGG19 model achieved 98.81% validation accuracy. Despite good accuracy, interpretation of the result still questionable. The proposed methodology integrates explainable AI (XAI) for brain tumor detection to interpret system decisions. The proposed study uses a gradient explainer to interpret classification results. Comparative statistical analysis highlights the effectiveness of the proposed explainer model over other XAI techniques.

Long non-coding RNAs (lncRNAs) exert significant influence on the development of cancer. However, their role in colorectal cancer (CRC) is not fully clarified. The expression levels of LINC01811 in CRC samples were determined using differential expression analysis and validated by RT-qPCR assays. Transwell assays were conducted to investigate the biological function of LINC01811 in CRC. To elucidate the mechanism by which LINC01811 acts as a molecular sponge for miR-214-3p and regulates YAP1 expression, binding site analysis, Luciferase reporter assay, RT-qPCR, and Western blotting were employed. We identified a novel oncogenic lncRNA LINC01811 in CRC tissues and cell lines. Our results showed that the suppression of LINC01811 significantly reduced CRC cell invasion and migration by regulating epithelial-mesenchymal transition-related markers, including MMP2, MMP9, vimentin, and E-cadherin in vitro. Furthermore, LINCO1811 modulated YAP1 expression by sequestering miR-214-3p, thereby promoting CRC progression by suppressing its activity. In summary, this study identified a novel lncRNA LINC01811 involved in CRC progression through the miR-214-3p/YAP1 axis.

The online version contains supplementary material available at 10.1007/s13205-025-04292-8.

Abnormal tumor blood vessels can significantly promote the malignant progression of tumors, prompting researchers to focus on drugs that normalize these vessels for clinical treatment. The combination of the Qi-tonifying drug Astragali Radix and the blood-activating drug Curcumae Rhizoma, referred to as AC, exhibited significant anti-tumor metastasis effects. However, the association between the anti-tumor metastasis effect of AC and its potential role in regulating tumor vascular remodeling warrants further exploration.

This study aimed to elucidate the mechanism through which AC induces tumor blood vessel normalization in colon cancer (CC).

The potential active components of AC were identified through UPLC-MS/MS. An orthotopic transplantation model of CC was established in BALB/c mice using the CT26-Lucifer cell line, and the effects of AC were evaluated using IVIS imaging, hematoxylin and eosin (H&E) staining, and immunohistochemistry. Network pharmacology and molecular biology analyses were employed to identify the potential direct targets of AC. Subsequently, RT-PCR and Western blotting techniques were utilized to validate the findings obtained from network pharmacology. Furthermore, ELISA and other methodologies were used to investigate glycolysis-related indicators, along with immunofluorescence technology to demonstrate changes in vascular leakage and perfusion characteristics associated with blood vessel normalization.

We identified HIF-1α as a potential direct target of AC. This interaction influences the glycolytic processes in both tumor cells and tumor-associated endothelial cells (TECs) by directly binding to HIF-1α and modulating its nuclear translocation, thereby determining the integrity of TEC junctions. Mechanistically, AC directly regulates the key enzyme PFKFB3 in glycolysis by modulating HIF-1α expression and inhibiting its nuclear translocation. This action reduces tumor glycolytic flux, decreases the internalization of VE-cad, and influences the expression of downstream matrix metalloproteinases (MMPs), thereby strengthening the adherens and tight junctions between TECs and restoring vascular integrity.

This study presents novel findings that AC can regulate glycolysis through the inhibition of HIF-1α nuclear translocation, thereby promoting the normalization of tumor blood vessels and effectively inhibiting tumor metastasis. These results suggested that AC may serve as an effective therapeutic agent for normalizing tumor blood vessels.

Ginseng peptides, small molecule active ingredients in ginseng, are mainly extracted naturally or synthesized chemically, but high costs and difficulties hinder further research. In this study, a ginseng hexapeptide FKEHGY, named antitumor peptide 0601 (AT0601) and its five tandem sequence repeats AT0605, were expressed in Bacillus subtilis WB600 for the first time, and the bioactivity study showed that the anticancer activity of AT0605 was even significantly higher than that of AT0601 for colon cancer CT26 cells, with IC50s of 16.82 ± 1.3 μM (48 h) and 855.57 ± 6.04 μM (48 h), respectively, i.e. AT0605 achieves the same inhibition rate for CT26 cells at a concentration 50 times lower than that of AT0601. Similar to the ginseng peptide AT0601, recombinant AT0605 also inhibited cell growth by blocking cells in the G1 phase and activated the mitochondria-associated caspase pathway to induce apoptosis. In conclusion, all two kinds of the recombinant ginseng peptides could also inhibit cell proliferation through mechanisms such as inhibiting cell cycle arrest and inducing a decrease in mitochondrial membrane potential.

Curcumin, a phenolic compound derived from turmeric, has demonstrated anti-tumor properties in preclinical models of various cancers. However, the exact mechanism of curcumin in treating bladder cancer remains unclear. This study aimed to elucidate the therapeutic targets and molecular mechanisms of curcumin in the treatment of BC through an integrated approach of network pharmacology, molecular docking, and molecular dynamics simulations. PharmMapper, SuperPred, TargetNet, and SwissTargetPrediction were utilized to acquire targets associated with curcumin, while GeneCards, CTD, DisGeNET, OMIM, and PharmGKB databases were utilized to obtain targets related to bladder cancer. The drug-disease interaction targets were obtained using Venny 2.1.0, and GO and KEGG enrichment analyses were then conducted with the DAVID tool. We constructed a protein-protein interaction (PPI) network and identified tenkey targets. In conclusion, AutoDock Tools 1.5.7 was utilized to conduct molecular docking simulations, followed by additional analysis of the central targets through the GEPIA, HPA, cBioPortal, and TIMER databases. A total of 305 potential anticancer targets of curcumin were obtained. The analysis of GO functional enrichment resulted in a total of 1105 terms, including 786 terms related to biological processes (BP), 105 terms related to cellular components (CC), and 214 terms related to molecular functions (MF). In addition, KEGG pathway enrichment analysis identified 170 relevant signaling pathways. Treating bladder cancer could potentially involve inhibiting pathways like the PI3K-Akt signaling pathway, MAPK signaling pathway, EGFR tyrosine kinase inhibitor resistance, and IL-17 signaling pathway. Activating TNF, ALB, CASP3, and ESR1 while inhibiting AKT1, EGFR, STAT3, BCL2, SRC, and HSP90AA1 can also hinder the proliferation of bladder tumor cells. According to the results of molecular docking, curcumin binds to these central targets in a spontaneous manner, exhibiting binding energies lower than - 1.631 kJ/mol. These findings were further validated at the transcriptional, translational and immune infiltration levels. By utilizing network pharmacology and molecular docking techniques, it was discovered that curcumin possesses diverse effects on multiple targets and pathways for treating bladder cancer. It has the potential to impede the growth of bladder tumor cells by suppressing various pathways including the PI3K-Akt and MAPK signaling pathways, as well as pathways associated with EGFR tyrosine kinase inhibitor resistance and the IL-17 signaling pathway. Curcumin could potentially disrupt the cell cycle advancement in bladder cancer cells by increasing the expression of TNF, ALB, CASP3, and ESR1 while decreasing AKT1, EGFR, STAT3, BCL2, SRC, HSP90AA1, and other targeted genes. These findings reveal the possible molecular pathways through which curcumin exerts its anticancer effects in bladder cancer, and this novel research strategy not only provides an important basis for an in-depth understanding of the anticancer mechanism of curcumin, but also offers new potential drugs and targets for the clinical treatment of bladder cancer. Therefore, this study is of great scientific significance and practical application value for promoting the development of bladder cancer therapeutic field. This finding provides strong support for the development of novel, safe and effective drugs for bladder cancer treatment.

Monoclonal antibodies (mAbs) have revolutionized the treatment of multiple myeloma (MM), demonstrating remarkable effectiveness, despite potential adverse events (AEs). This study aims to identify unexpected signals of disproportionate reporting (SDRs) for cardiovascular (CV) and respiratory AEs associated with mAbs in MM treatment.

From January 2015 to December 2023, reports involving suspected drugs (daratumumab, elotuzumab, elranatamab, isatuximab, belantamab mafodotin, teclistamab, and talquetamab) were analyzed in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. Descriptive analysis was followed by disproportionality analyses first comparing mAbs to all other drugs (reference group, RG1), and subsequently conducting a sensitivity analysis against other MM drugs (RG2).

Out of 13,496,241 reports, 31,052 (0.2%) were associated with MM, with 6574 (0.1%) linked to CV and respiratory adverse events, primarily involving older population (n = 3441; 52.3%) and male (n = 3338; 50.8%) patients. Disproportionality analyses identified unexpected SDRs for daratumumab, including cardiac failure (n = 322; RG1: ROR = 4.74, CI 95% = 4.24-5.29; RG2: ROR = 4.42, 95% CI = 3.91-4.99), embolic and thrombotic event, such as pulmonary embolism (162; RG1: 2.44, 2.09-2.85), deep vein thrombosis (126; RG1: 2.95, 2.47-3.52), and respiratory failure (192; RG1: 4.06, 3.52-4.68; RG2: 4.2, 3.59-4.91). Isatuximab was linked to cardiac arrhythmia, such as atrial fibrillation (46; RG1: 2.54, 1.9-3.4; RG2: 1.35, 1.01-1.81), embolic and thrombotic event, including deep vein thrombosis (26; RG1: 2.93, 1.99-4.3) and pulmonary embolism (89; RG1: 6.56, 5.32-8.1; RG2: 2.93, 2.37-3.63). Elotuzumab showed also SDRs for atrial fibrillation (56; RG1: 3.68, 2.82-4.79; RG2: 1.96, 1.5-2.56) and deep vein thrombosis (41; RG1: 5.49, 4.03-7.47).

Unexpected CV and respiratory AEs with clinical relevance not previously reported in literature have been identified underlining the importance of pharmacovigilance.

Exploring the potential of BOLA3-DT as a diagnostic biomarker in prostate cancer.

Expression of the lncRNA BOLA3-DT was analyzed between normal and tumor samples in the GDC TCGA PRAD (Genomic Data Commons: The Cancer Genome Atlas Prostate Adenocarcinoma Collection) dataset. Disease progression-related clinicopathological parameters such as serum PSA level (ng/ml) and Gleason score were associated with the expression of BOLA3-DT using the same GDC TCGA PRAD dataset. To validate these findings, the expression of BOLA3-DT was checked in our sample set of 15 PCa (prostate cancer) and 15 BPH (benign hypertrophy of the prostate) patients.

In the GDC TCGA PRAD dataset, the expression of the lncRNA BOLA3-DT was significantly downregulated in prostate cancer tissue samples (n = 492) compared to adjacent normal (n = 52; p < 0.0001), and, there was a significant negative correlation between the expression of the lncRNA BOLA3-DT and the serum PSA level (p < 0.01). However, no significant association was found between the lncRNA BOLA3-DT expression and the Gleason score (p > 0.05). In this study, it was found that BOLA3-DT was downregulated in PCa tissue samples compared to BPH samples (p > 0.05). In the GDC TCGA PRAD dataset, it was revealed that BOLA3-DT could serve as an excellent diagnostic marker with a sensitivity of 86.9% and a specificity of 84.6% (AUC-0.916).

LncRNA BOLA3-DT, a novel long non-coding RNA, was found to be downregulated in prostate cancer. The expression of the lncRNA BOLA3-DT can serve as a diagnostic marker in prostate cancer.

The objective of this study is to determine an optimal threshold for the maximum standardized uptake value (SUVmax) of 18 F-fluorodeoxyglucose PET/CT to predict the newly proposed high-grade tumor classification and assess its prognostic significance in invasive lung adenocarcinoma (LUAD).

Surgical specimens from 185 patients with pathological stage I invasive LUAD in the training group, along with 90 patients in the validation group, were analyzed using the novel IASLC grading system. The receiver operating characteristic curve was used to determine the optimal SUVmax threshold and assess its predictive accuracy. Disease-free survival (DFS) and overall survival (OS) were analyzed using Kaplan-Meier survival curves and Cox regression analysis.

Linear correlation analysis demonstrated a significant positive association between SUVmax and the proportion of high-grade histological patterns ( R ² = 0.346, P  < 0.001). The optimal SUVmax cutoff for predicting grade 3 tumors was 3.8, with an area under the curve of 0.866 in the training dataset and 0.899 in the validation dataset. Multivariate logistic regression analysis identified an SUVmax >3.8 as an independent predictor of grade 3 tumors ( P  < 0.001). In Cox regression analysis, SUVmax >3.8 was independently associated with reduced DFS (HR = 4.009, 95% CI: 1.568-10.250, P  = 0.004) and OS (HR = 5.536, 95% CI: 1.175-26.075, P  = 0.030).

As a noninvasive preoperative parameter, SUVmax >3.8 is a significant indicator of high-grade tumors as classified by the IASLC grading system and is strongly associated with worse DFS and OS.

Prostate cancer (PCa) is the most commonly diagnosed cancer in men in the United States, following skin cancer, with an incidence rate of 112.7 per 100,000 men per year. The need for a reliable, non-invasive diagnostic tool for early PCa detection (screening, biochemical residual disease) remains unmet due to the limitations of PSA testing, which often leads to overdiagnosis and overtreatment. The PROSTest is a novel, blood-based qPCR assay that assesses gene expression to diagnose PCa and predict patient outcomes to different treatments. This study aimed to validate the sensitivity and specificity of the PROSTest in a diverse cohort of US-based PCa patients compared to healthy controls.

This prospective study included 143 PCa patients and 92 healthy controls. Blood samples were collected, and the PROSTest was conducted following RNA isolation and cDNA production, using a predefined 27-gene algorithm to provide a binary output. The assay's sensitivity and specificity were evaluated using receiver operating characteristic (ROC) analysis, with a 50% score cut-off distinguishing PCa from non-PCa patients. Analytical reproducibility was assessed with intra- and inter-assay comparisons of Ct values and PROSTest scores.

The PROSTest demonstrated a sensitivity of 94% (95% CI 89-98%) and a specificity of 88% (95% CI 80-94%) in distinguishing PCa patients from controls, with an area under the ROC curve (AUROC) of 0.97. The false positive rate among controls was 12%. Intra- and inter-assay reproducibility was confirmed with no significant differences in Ct values or PROSTest scores between operators or assays. PROSTest scores were significantly higher in PCa patients compared to controls and in those undergoing treatment versus untreated patients.

This validation study confirms the high sensitivity and specificity of the PROSTest in detecting PCa in a diverse USA cohort. The assay's robustness and reproducibility support its potential as a reliable diagnostic tool for PCa detection and monitoring. Further studies are warranted to evaluate its utility across broader populations and treatment settings.

Brain metastasis (BM) is a significant factor contributing to the poor prognosis of patients with non-small cell lung cancer (NSCLC). Secreted phosphoprotein 1 (SPP1) is implicated in the progression and metastasis of several cancers. The role of SPP1 in NSCLC remains unclear, especially in NSCLC BM. This study aimed to identify genes associated with NSCLC BM and to investigate the involvement of SPP1 in NSCLC BM. Integrated genomic analysis was utilized to identify candidate genes in NSCLC. The expression levels of SPP1 were evaluated in NSCLC tissues and cell lines. In vitro and in vivo experiments were conducted to assess the effect of SPP1 on NSCLC cell behavior and BM. The potential mechanisms of SPP1 were demonstrated by CO-IP and liquid chromatography-mass spectrometry (LC-MS). The underlying mechanism involving the PI3K/AKT/mTOR pathway was explored. The results showed that SPP1 expression was upregulated in NSCLC tissues and cell lines. Depletion of SPP1 using shRNA inhibited cell proliferation, migration, and invasion in vitro and suppressed BM in vivo. Mechanistically, SPP1 facilitates the ubiquitination of P85α by interacting with the ubiquitin ligase RNF114, thus playing a role in regulating NSCLC BM through the PI3K/AKT/mTOR signaling pathway. Moreover, immunohistochemistry staining confirmed higher expression of SPP1 in NSCLC tissues with BM compared to those without BM. In summary, elevated SPP1 expression was associated with poor clinical outcomes in NSCLC patients. This study highlights the role of SPP1 as a regulator of cell metastasis and suggests its potential as a novel therapeutic target for BM in NSCLC.

The initiation and progression of clear cell renal cell carcinoma (ccRCC) are closely linked to significant metabolic alterations. Specifically, lipid metabolism alterations and their association with the high invasiveness in ccRCC require further investigation. After conducting RNA-sequencing (RNA-seq), we discovered that Hydroxyacyl-CoA Dehydrogenase Trifunctional Multienzyme Complex Subunit Beta (HADHB) was significantly downregulated in the highly invasive ccRCC cell line. It was found that the expression of HADHB in ccRCC tumor tissues was lower than that in paracancer tissues, which is associated with poor patient prognosis. Subsequently, we confirmed that highly invasive ccRCC exhibited an increased lipid accumulation due to the suppression of mitochondrial fatty acid transport and enhanced conversion of fatty acids to triglycerides within cancer cells. Specifically, the downregulation of HADHB inhibited mitochondrial fatty acid β-oxidation (FAO) in cancer cells, leading to partial impairment of mitochondrial function and decreased ATP production. However, this trade-off involving the reduction of a high-yield ATP production conferred an advantage by reducing reactive oxygen species (ROS) generation within cancer cells, thereby protecting them from oxidative stress and enhancing their invasive potential. Furthermore, the downregulation of HADHB promoted epithelial-mesenchymal transition (EMT) and angiogenesis in cancer cells, accelerating the progression of ccRCC and endowing ccRCC cells with metastatic capabilities.

Non-small cell lung cancer (NSCLC) is a prominent cause of cancer death worldwide. Sennoside A (SA) is the primary anthraquinone active component from Rheum officinale Baill and exerts antitumor functions in multiple human tumors. This research aimed to elucidate the function and mechanism of SA in NSCLC. SA functions in NSCLC were determined using Cell Counting Kit-8 (CCK-8) assay, Terminal deoxynucleotidyl transferase dUTP nick-end labeling analysis, Transwell assay, Enzyme-Linked Immunosorbent Assay (ELISA), and Western blot. Meanwhile, the SA mechanism in NSCLC was examined with Western blot, immunofluorescence assay, CCK-8 assay, Transwell analysis, and ELISA. Furthermore, SA functions in NSCLC growth in vivo were assessed by the establishment of a tumor xenograft model, hematoxylin-eosin staining, analysis of NSCLC tissue apoptosis, and immunohistochemistry assays. Functionally, less than 200 µM SA had no significant effect on normal human bronchial epithelial cell BEAS-2B cell viability. Furthermore, H460 cell viability was decreased when the SA dose was greater than or equal to 25 µM (IC50 = 53.34 µM). A549 cell viability was reduced when the SA dose was greater than or equal to 12.5 µM (IC50 = 48.21 µM). Also, SA repressed NSCLC cell proliferation and boosted cell apoptosis. SA restrained NSCLC cell invasion and tumor microenvironment. Mechanically, SA weakened NSCLC cell proliferation, invasion, and tumor microenvironment, yet this impact was abolished after transfecting pcDNA3.1-TRAF6, which indicated that SA repressed NSCLC cell proliferation, invasion, and tumor microenvironment through inactivating TRAF6/NF-κB. Moreover, SA reduced subcutaneous tumor volume and promoted NSCLC tissue apoptosis in vivo. SA repressed NSCLC cell proliferation, invasion, and tumor microenvironment through inactivating TRAF6/NF-κB.

A series of 6,7-dimethoxy-4-anilinoquinazoline derivatives, which have amidine (4a-4d, 5a-5c, 6a-6d) and amidoxime (4e, 5d, 6e) moieties, were synthesized and evaluated their anticancer activity on various cancerous cell lines (H1975, HCC827, and H23). Among the synthesized compounds, 4c was found to be the most potent inhibitor of EGFR, comparable to erlotinib, with higher than 10 μM EC50 values for H1975 and H23 and 0.16 μM EC50 value for HCC827 cells. 4c activated mitochondrial apoptosis signaling and suppresses EGFR downstream signaling, such as ERK1/2 and PI3K/Akt pathways in HCC827 NSCLC cells (EGFR Del19) as erlotinib. Molecular docking and molecular dynamics simulations studies were performed to evaluate the interaction and binding energies of all synthesized compounds against EGFR wild type, EGFR T790M/L858R, EGFR L858R, and EGFR exon-19 deletion mutant (del-747-749). 4c showed a similar binding profile with erlotinib as stable binding interaction values. Also, 4c formed additional hydrogen bonds via the amidine group in its structure, potentially increasing its affinity and stability within the binding pocket. Hence, 4c was selected as a lead compound for further pharmacomodulation.

Myxoid pleomorphic liposarcoma is a rare and aggressive subtype of soft tissue sarcomas (STS). It primarily arises from adipose tissue and exhibits a high rate of recurrence and metastatic potential. We report the case of a 35-year-old male gym trainer with a 5-month history of a painless, progressively enlarging mass on the right posterior aspect of chest, diagnosed with myxoid pleomorphic liposarcoma following imaging and histopathological evaluation of the excised specimen. Surgical excision with clear margins and adjuvant radiotherapy resulted in a favorable outcome with no recurrence at 7 months. This case emphasizes the importance of early diagnosis and multidisciplinary approach in managing a rare soft tissue sarcoma to prevent complications from a delayed intervention.

Immune checkpoint inhibitor plus chemotherapy (ICT) is the standard treatment for extensive-stage small cell lung cancer (ES-SCLC). We previously reported that oligometastasis (OM) is a predictor of ICT efficacy, however, the relationship between ICT efficacy and OM in older patients remains unknown. Therefore, this study examined the efficacy of ICT in the older patients including the influence of OM.

We enrolled patients with ES-SCLC who received ICT as first-line treatment between September 2019 and June 2022. Patient characteristics and treatment efficacy were compared between older (≥75 years) and non-older (<75 years) patients.

We enrolled 228 patients, including 42 older patients. The prevalence of synchronous oligometastasis (SOM) at the start of first-line treatment was 21.0 % and 21.4 % (p = 1.0) in the older and non-older groups, respectively. The progression-free survival (PFS) with first-line therapy was 5.4 and 4.5 months (p = 0.55) and overall survival (OS) was 11.5 and 12.6 months (p = 0.74) for the SOM and non-SOM subgroups in the older group, respectively. For second-line treatment, PFS was 4.5 and 6.3 months (p = 0.79), and OS after second-line initiation was 16.0 and 13.2 months (p = 0.55) in oligoprogression (OP) and non-OP patients in the older group, respectively.

The frequencies of SOM and OP were not significantly different between older and non-older patients. Although the small number of older patients in this study makes it impossible to conclude definitively, we did not observe a significant prognostic prolongation in older patients with OM as in non-older patients.

Breast cancer (BC) is the most common malignant tumor and the leading cause of cancer-related deaths among women worldwide. Great progress has been recently achieved in controlling breast cancer; however, mortality from breast cancer remains a substantial challenge, and new treatment mechanisms are being actively sought. Programmed cell death (PCD) is associated with the progression and treatment of many types of human cancers. PCD can be divided into multiple pathways including autophagy, apoptosis, mitotic catastrophe, necroptosis, ferroptosis, pyroptosis, and anoikis. Ubiquitination is a post-translational modification process in which ubiquitin, a 76-amino acid protein, is coupled to the lysine residues of other proteins. Ubiquitination is involved in many physiological events and promotes cancer development and progression. This review elaborates the role of ubiquitin-specific protease (USP) in programmed cell death, which is common in breast cancer cells, and lays the foundation for tumor diagnosis and targeted therapy.

Silver nanoparticles (AgNPs) are increasingly known to have anticancer effects, but few studies have examined their adverse effects, so the underlying mechanisms are not yet fully understood. The current study investigated the critical influence of AgNPs on angiogenesis in 4T1 breast cancer-bearing mice.

The sub-lethal dose of AgNPs (0.25 mg/kg) was carried out. Female BALB/c mice (N = 35) were divided into 7 groups; normal control, cancer control, AgNPs control (one dose of (0.25 mg/kg) AgNPs), single dose AgNPs before cancer, single dose AgNPs after cancer, 5 doses AgNPs after cancer, and doxorubicin. 4T1 breast cancer cell induction was performed subcutaneously on the left flank. Intraperitoneal (IP) administration of AgNPs and doxorubicin was carried out for all studied groups.

Weight gain was normal in all study groups except the doxorubicin-treated group. Administering AgNPs before cancer induction promotes tumorigenesis, raises MMP-2 and MMP-9 activity, and increases CD31 and Ki67 expression. The cancer control group experienced the same outcomes. On the other hand, depending on the administered doses, the injection of AgNPs after tumor induction resulted in a notable decrease in tumor volume. In the doxorubicin-treated group, similar results were observed, while a dose of AgNPs‌ before cancer induction lead to increasing tumor volume compared to the cancer control group. The differences of biochemical markers including LDH, ALP, AST, ALT, BUN, and Cr between different groups were not significant. Significant differences were seen among all studied groups except doxorubicin and single dose AgNPs before cancer groups for serum TAC levels.

It appears that AgNPs are considered a double-edged sword in the fight against cancer. AgNPs not only have anti-cancer effects on tumor size and angiogenesis, but they also might have cancer-stimulating roles. To confirm this conclusion, more detailed investigations are needed.

Clear cell renal cell carcinoma (ccRCC) accounts for 70% of renal cell carcinoma (RCC) cases. Although surgery remains the mainstay treatment, renal injury and high metastasis rates after nephrectomy dramatically reduce patient quality of life. Drugs that stimulate the immune system by targeting checkpoint pathways improve overall survival in patients with RCC. Here, we investigated the applicability of lysophosphatidylcholine acyltransferase 3 (LPCAT3) as a target for immunotherapy.

In the present study, high LPCAT3 expression in ccRCC was identified using The Cancer Genome Atlas (TCGA) data and validated in two external cohorts from the Gene Expression Omnibus (GEO) database. qRT-PCR was performed to identify the mRNA level of LPCAT3 in tumors and adjacent normal tissues. And immunohistochemistry was used to evaluate the protein level of LPCAT3 between two groups of samples. Furthermore, gene set enrichment analysis was performed to explore the biological processes and pathways related to LPCAT3 expression. Key gene expression and correlation analyses were performed to determine the crosstalk among LPCAT3 expression, ferroptosis, and endoplasmic reticulum stress (ERS). Subsequently, CIBERSORT was used to analyze the immune infiltration status of patients with high and low LPCAT3 expression.

TCGA and GEO data revealed that LPCAT3 expression in ccRCC tumor tissues was higher than that in adjacent normal tissues; moreover, patients with high LPCAT3 expression had better survival outcomes. qRT-PCR and immunohistochemistry verified the high LPCAT3 expression in tumor tissue. Pathways related to ferroptosis and ERS were upregulated in patients with high LPCAT3 expression. Univariate and multivariate regression analyses revealed that low LPCAT3 levels represent an independent risk factor for ccRCC. LPCAT3 expression was positively correlated with M2 macrophage infiltration levels but negatively correlated with the memory B cell, CD8+ T cell, follicular helper T cell, regulatory T cell, activated natural killer cell, and activated memory CD4+ T cell infiltration levels.

LPCAT3was identified as a ccRCC biomarker and may regulate immune infiltration and prognosis in ccRCC by mediating ferroptosis and ERS. Thus, it has potential for exploitation as a prognostic and immune therapeutic target for patients with ccRCC.

To explore the role of GFPT2 in the sensitivity of STK11/KRAS lung cancer cells to cisplatin chemotherapy, and its underlying mechanism.

A549 and H460 cells were used to analyze the effect of GFPT2 on cisplatin chemotherapy sensitivity, as both carry KRAS mutations and H460 has LKB1 inactivation mutations, meeting the requirements of a KRAS/LKB1 co mutant tumor model. The levels of UDP-GlcNAc, OGT, OGA, and O-GlcNAc in the HBP pathway were also determined. To verify the potential role of HBP, we added OGT inhibitors. In vivo, we constructed a nude mouse model bearing A549 tumor to further validate the results of in vitro cell experiments.

GFPT2 silencing can significantly inhibit cell proliferation, invasion, and migration, promote cell apoptosis, and enhance the effect of cisplatin (p < 0.05). After OSMI-1 processing, GFPT2 enhances O-GlcNAc modification levels via the OGT-mediated HBP, thereby decreasing the sensitivity of STK11/KRAS mutant cells to cisplatin chemotherapy. In addition, GFPT2 silencing enhances the chemotherapy sensitivity of cisplatin and inhibits tumor growth, while overexpression of GFPT2 weakens this effect (p < 0.05). The above results provide new targets and combination therapy options for the clinical treatment of KRAS/LKB1 mutant lung cancer.

Our study found that inhibiting GFPT2 can enhance the chemotherapy sensitivity of cisplatin to STK11/KRAS/LKB1 mutant NSCLCs cells through the OGT mediated HBP pathway, filling a key gap in the chemotherapy resistance mechanism of KRAS/LKB1 mutant lung cancer.

To calculate national trends and estimates of cancer-related hospitalizations, hospital outcomes, and hospitalization costs. The current study was a retrospective analysis of National Inpatient Sample data, collected during 2008 to 2019. Adult cancer hospitalizations were identified by Clinical Classifications Software codes. We estimated weighted frequencies, proportions, and trends in cancer-related hospitalizations, hospital outcomes, and hospitalization costs. The primary outcome of the study was cancer-related hospitalizations, and secondary outcomes were the reasons for hospitalization, disposition status, hospital length of stay, and hospitalization cost. There were 371 million weighted hospitalizations during 2008 to 2019, of which 15.1% (56 million) were cancer related. The most common cancer types were breast cancer (11.9%), secondary malignancies (11.2%), and prostate cancer (10.3%), and the most common reasons for cancer-related hospitalizations were septicemia (4.8%), pneumonia (4.7%), and complications of surgical procedures or medical care (3.1%). Trend analysis showed that the total number of cancer-related hospitalizations increased from 12,963 to 16,500 per 100,000 hospitalizations during the study period (relative increase, 27.3%). Mortality rates decreased from 5.1% to 4.0% (relative decrease, 21.6%), while hospital length of stay decreased from 3.5 to 3.2 days (relative decrease, 8.6%), during the study period. Disposition to home or short-term facilities decreased (relative decrease, 3.1%), while to long-term facilities increased (relative increase, 20.6%) during the same period. Total hospitalization cost increased from $55.5 billion in 2008 to $76.4 billion in 2019 (relative increase, 37.7%). Our study provides preliminary estimates and findings for developing an evidence base for understanding cancer-related hospitalizations.

This study aimed to explore the risk of stroke death (SD) in cancer patients, estimate rates, and identify risk factors associated with SD.

In this retrospective study, we used the 17 National Cancer Institute Surveillance, Epidemiology, and End Results registries (2000-2020). A total of 5,922,533 patients diagnosed with their first primary cancer were included. The primary outcome was the standardized mortality ratio (SMR) of SD in cancer patients. Secondary outcomes included SD incidence rates and risk factors. Rates were calculated per 100,000 persons with the annual percentage change (APC).

Among included patients, 56,686 (2.0 %) died due to stroke. Compared to the general population, younger patients (≤39 years) (SMR: 2.31) and patients receiving no treatment (SMR: 1.36) had the highest risk. Cancer types with the fastest-declining SD rates were in the male genital (APC: -13.9 %) and breast (APC: -11.8 %). Older age (hazard ratio [HR]: 1.11, p < 0.001), male sex (HR: 1.06, p < 0.001), and non-white race (HR: 1.13, p < 0.001) were associated with increased risk of SD. Cancers of the nervous system (HR: 3.42, p < 0.001), respiratory (HR: 1.38, p < 0.001), and head and neck (HR: 1.37, p < 0.001) had higher risk of SD vs. breast cancer. Patients with primary chemotherapy (HR: 0.69, p < 0.001) and radiotherapy (HR: 0.69, p < 0.001) demonstrated less risk vs. those without treatment.

SD has declined over the years for both sexes and all cancer types. Older age, non-white race, and certain cancers (nervous system, respiratory system, and head and neck) pose significant risks for SD.

The formation of purinosomes, dynamic complexes involved in de novo purine biosynthesis, has been recognized as a critical process for cell growth. Although their upregulation in cancer cells suggests their potential as a therapeutic target, the specific role of purinosomes in hepatocellular carcinoma (HCC) remains uncertain. The purinosome score was found to have prognostic value. Enrichment analyses indicated a connection between purinosome-related genes and cell cycle regulation. Moreover, our research has demonstrated a correlation between the upregulation of genes associated with purinosomes and the enhanced formation of purinosomes in Huh-7 cells. Pyrimethamine has been identified as a promising therapeutic option for targeting purinosome to exert anti-cancer effects. Furthermore, the purinosome score exhibited an positive relationship with the response to immunotherapy. It may guide the stratification of liver cancer patients and screen for populations that may benefit from immunotherapy. This study examines the prognostic and predictive value of purinosome in liver cancer, suggesting that targeting purinosome formation with pyrimethamine or immunotherapy could benefit patients with high purinosome scores.

Non-small cell lung cancer (NSCLC) can arise from insertions in exon 20 of the EGFR gene, among other alterations. We carried out an external quality assessment (EQA) to evaluate the accuracy of laboratory methods and to highlight the importance of detecting and identifying genetic alterations, such as EGFR exon 20 insertion, in patients with NSCLC.

The 2021 EGRF exon 20 EQA program consisted of two rounds, in which four formalin-fixed paraffin-embedded specimens (round 1: two positive for EGFR exon 20 insertions/duplications, one positive for a common EGFR alteration, and one wild-type; round 2: three positive for EGFR exon 20 insertions/duplications and one wild-type) obtained from patients with NSCLC were tested.

Approximately 80% of the invited laboratories participated in each round. The most common DNA isolation techniques used were the cobas® DNA Sample Preparation Kit (46.7%) in round 1 and QIAamp (37.1%) in round 2. The most frequently used genotyping method in both rounds was the cobas® EGFR Mutation Test (round 1: 53.3%; round 2: 37.1%). In both rounds, 71.1% and 73.6% of the tests, respectively, reported the expected result. The lowest success rate was observed in the H773delinsRY Exon 20 determination (round 1: 17.8%; round 2: 31.4%). This alteration was correctly determined only by next-generation sequencing.

The variability in the genotyping methods and the success rate obtained in our study highlight the importance of EQA in Spain to ensure high performance.

Soft tissue sarcomas (STS) are a rare group of malignant tumors originating from soft tissues. The study systematically evaluates the global burden of soft tissue and extraosseous sarcomas from 1990 to 2021 across diverse populations.

We examined incidence, mortality, and disability-adjusted life years (DALYs) using data from the Global Burden of Disease (GBD) 2021 database. Estimated annual percentage change (EAPC) assessed trends from 1990 to 2021. Cross-country inequality was evaluated using the socio-demographic index (SDI), inequality slope index, and concentration index. Decomposition analysis identified key drivers of changes in disease burden. Frontier analysis pinpointed countries with potential for improvement, while Bayesian age-period-cohort (BAPC) projected trends through 2036.

Although the absolute numbers of cases, deaths, and DALYs increased, the global age-standardized incidence rate (ASIR), mortality (ASMR), and DALYs (ASDR) decreased. Males consistently exhibited higher rates than females, with the highest rates in individuals aged 95 and older. In high-SDI regions, ASIR slightly increased, whereas ASMR and ASDR decreased. The gap between high- and low-SDI countries widened over time. Projections indicate that by 2036, absolute numbers will increase, while age-standardized rates will further decline.

Despite the increasing absolute burden, the global age-standardized rates have declined, likely reflecting multiple contributing factors. However, the persistent disparities underscore the need for improved access to care and targeted public health interventions to mitigate the global burden.

This study evaluated the effectiveness and safety of tislelizumab plus lenvatinib (TL group) and tislelizumab monotherapy (T group) in patients with stage C hepatocellular carcinoma (HCC) according to the Barcelona Clinic Liver Cancer (BCLC) staging system after lenvatinib failure, and it analyzed the factors influencing the effectiveness of TL as a second-line treatment. This retrospective analysis involved 51 patients treated at a single center between January 2019 and July 2023. Survival outcomes and tumor responses were compared between the TL and T monotherapy groups. Prognostic factors for overall survival (OS) and progression-free survival (PFS) were identified using Cox proportional hazard regression models. Among patients with BCLC stage C advanced HCC who experienced lenvatinib treatment failure, median PFS was significantly longer in the TL group than in the T group (6.8 months vs. 4.5 months, p = 0.003), and OS was notably extended in the TL group (14.0 months vs. 10.4 months, p = 0.012). Although the disease control rate (64% vs. 53.8%, p = 0.461) and objective response rate (20% vs. 7.7%, p = 0.202) were numerically higher in the TL group, these differences did not reach significance. Child-Pugh B liver function and tislelizumab monotherapy were independent prognostic factors for poor OS, whereas only tislelizumab monotherapy was an independent prognostic factor for poor PFS, Child-Pugh B was not a prognostic factor for PFS. Subgroup analysis demonstrated the OS benefit of tislelizumab plus lenvatinib in patients with Child-Pugh A liver function (14.0 months vs. 12.0 months, p = 0.013) but not in those with Child-Pugh B liver function (7.7 months vs. 6.1 months, p = 0.225). In the TL group, the most frequent treatment-related adverse events (AEs) were hand-foot skin reaction (32%), hypertension (28%), diarrhea (32%), and hypothyroidism (20%). Grade 3 or higher AEs occurred in 24% of patients in the TL group, and hand-foot skin reaction and diarrhea were the most frequent grade 3 or higher AEs. The incidence of AEs was comparable between the two groups. As a second-line treatment, the combination of tislelizumab and lenvatinib was well tolerated and associated with improved OS and PFS versus tislelizumab alone for patients with advanced HCC, particularly in those with Child-Pugh A liver function.

Colorectal cancer (CRC) is a leading contributor to global cancer-related morbidity and mortality. Glycosylation is a common post-translational protein modification. Aberrant protein glycosylation is a hallmark of cancer, affecting biological processes and driving malignant CRC phenotypes. Specifically, abnormal N-glycosylation manifests as structural alterations in high mannose, sialylated, and fucosylated structures, collectively promoting cancer stemness and invasiveness. Concurrently, O-GlcNAcylation facilitates tumorigenesis through metabolic reprogramming and oncogene activation. Dysregulated mucin-type O-glycans (e.g., Core-1/Core-3 imbalance) and elevated SLex/SLea antigen expression are significantly correlated with tumor adhesion, metastatic dissemination, and adverse clinical outcomes. Furthermore, protein glycosylation contributes to chemoresistance through anti-apoptotic mechanisms, aberrant signaling activation, and pro-angiogenic pathways. This review systematically examines the dynamic evolution of protein glycosylation during CRC progression from normal mucosa to adenoma to adenocarcinoma. It also evaluates the CRC diagnostic and therapeutic implications of glycoproteins and glycans. This review can provide a molecular understanding for advancing CRC diagnostics and treatment.