Translational Oncology[JOURNAL]
Sun
200 papers
WDHD1 promotes hepatocellular carcinoma progression by affecting the cell cycle and immune evasion.
Xiang Z, Huang X, Zhu S … +5 more , Zhang X, Guo J, Chen Y, Huang Z, Hu S
Transl Oncol · 2026 May · PMID 41850053 · Full text
WD repeat and HMG-box DNA binding protein 1 (WDHD1) is dysregulated in various tumors; however, its role in hepatocellular carcinoma (HCC) remains unexplored. Herein, we observed that WDHD1 was significantly upregulated...
WD repeat and HMG-box DNA binding protein 1 (WDHD1) is dysregulated in various tumors; however, its role in hepatocellular carcinoma (HCC) remains unexplored. Herein, we observed that WDHD1 was significantly upregulated in HCC tissues and cell lines and correlated with poor prognosis. Regulatory analysis identified hsa-miR-22, hsa-miR-139, and the transcription factors EP300 and CREBBP as potential modulators of WDHD1. Functional assays revealed that WDHD1 knockdown suppressed cell proliferation, migration, and invasion, whereas its overexpression enhanced these oncogenic phenotypes both in vitro and in vivo. Furthermore, WDHD1 depletion promoted cellular apoptosis. Mechanistically, WDHD1 interacted with components of the CDC45-MCM-GINS (CMG) complex and maintained their structural integrity, thereby facilitating cell cycle progression. Drug sensitivity analysis indicated that elevated WDHD1 expression enhanced responsiveness to cell cycle-targeting agents. Additionally, high WDHD1 levels were associated with increased CD4 memory T cell infiltration, elevated tumor mutational burden (TMB), and enhanced expression of key immune checkpoint markers, suggesting a potential for improved response to immunotherapy in these patients. These findings suggest WDHD1 as a novel oncogenic driver and promising therapeutic target in HCC.
Impact of breast reconstruction and different surgical approaches after neoadjuvant therapy on the long-term survival of breast cancer patients.
Qiu Z, Zhang Y, Shou T … +3 more , Chen Y, Wang L, Wang Z
Transl Oncol · 2026 May · PMID 41850052 · Full text
INTRODUCTION: Large-scale studies on long-term survival after breast reconstruction (BR) following neoadjuvant therapy (NAT) are limited. This study compares long-term survival in breast cancer patients who had BR after...
INTRODUCTION: Large-scale studies on long-term survival after breast reconstruction (BR) following neoadjuvant therapy (NAT) are limited. This study compares long-term survival in breast cancer patients who had BR after NAT-either with nipple-sparing mastectomy (NSM) or total mastectomy (TM)-versus TM alone, to identify subgroups most likely to benefit. METHODS: We analyzed female breast cancer patients who received NAT in the SEER database, stratifying them into three groups: NSM with BR (n = 949), TM with BR (n = 3554), and TM without BR (n = 5465). Overall survival (OS) and breast cancer-specific survival (BCSS) were assessed using Cox proportional hazards models and propensity score matching (PSM). RESULTS: A total of 9968 patients were included in this study. Compared with TM alone, patients who underwent TM with BR had similar OS (Model 4, Table 3) and BCSS (HR: 0.90-0.96; all P > .05; Table 3). However, those who underwent NSM with BR were associated with better OS (HR: 0.29-0.60; all P < .05; Table 3) and BCSS (HR:0.31-0.64; all P < .05; Table 3). This association remained significant across PSM and multiple association inference models (Table 4) and was more robust in prespecified subgroups-including those aged <65 years and those with earlier-stage disease (Figure 3). CONCLUSIONS: This nationwide cohort study shows that, among patients receiving NAT, NSM with BR is associated with better OS and BCSS than TM alone-whereas TM with BR showed no survival benefit. NSM with BR is a feasible option for selected patients and warrants prospective validation.
Exploiting cellular senescence in hematologic malignancies.
Jiang P, Yang G, Li J … +6 more , Tian X, Yang X, Yang S, Wei J, Zhang X, Liu J
Transl Oncol · 2026 May · PMID 41844438 · Full text
Cellular Senescence is characterized by stable cell cycle arrest and major changes in cell morphology and physiology. Accumulating evidence indicates that senescence-associated phenotypic alterations in blood cells drive...
Cellular Senescence is characterized by stable cell cycle arrest and major changes in cell morphology and physiology. Accumulating evidence indicates that senescence-associated phenotypic alterations in blood cells drive the initiation and progression of hematologic malignancies. Therefore, we reviewed the phenotypes associated with cellular senescence and the regulatory mechanisms of cellular senescence in hematological malignancies. Notably, chemical induction of cellular senescence and selectively elimination of senescent cells can effectively inhibit tumor cell proliferation and enhance the efficacy of chemotherapy. This review also discusses the role of cellular senescence in the treatment of hematological malignancies, providing an in-depth understanding of the role of cellular senescence as a double-edged sword in cancer biology.
Personalized and HPV cancer vaccines in head and neck squamous cell carcinoma: from concept to clinical implementation.
Filippini DM, Le Tourneau C
Transl Oncol · 2026 May · PMID 41830840 · Full text
Head and neck squamous cell carcinoma (HNSCC) remains a challenging malignancy, with limited survival improvements despite recent advances with immune checkpoint inhibitors (ICIs). Within this context, personalized neoan...
Head and neck squamous cell carcinoma (HNSCC) remains a challenging malignancy, with limited survival improvements despite recent advances with immune checkpoint inhibitors (ICIs). Within this context, personalized neoantigen vaccines and HPV-targeted therapeutic vaccines are emerging as innovative strategies aimed at enhancing antitumor immunity. Personalized vaccines exploit tumor-specific mutational landscape to generate highly individualized T cell responses, demonstrating favorable safety profiles and durable immunogenicity in early-phase trials. Compounds such as TG4050, mRNA-4157, and PGV001 have shown early, hypothesis-generating signals of activity (from small early-phase studies), particularly in the adjuvant setting. HPV-targeted vaccines, including PDS0101, BNT113, and CUE-101, are being explored in HPV-positive HNSCC, mainly in combination with ICIs. While some early clinical activity has been observed, these signals should be interpreted cautiously given limited sample sizes, heterogeneous populations, and exploratory endpoints in many studies, and randomized trials such as ISA101b have failed to show survival benefits over ICIs alone. Overall, therapeutic vaccination appears safe and immunologically active, yet its efficacy is constrained by the immunosuppressive tumor microenvironment. The greatest clinical potential of therapeutic vaccination may lie in earlier disease stages, where the tumor burden is lower and immune modulation more feasible. Further clinical and translational research is needed to define the optimal integration of vaccine-based therapies into multimodal treatment paradigms for HNSCC.
Precision management of radiotherapy interruption in locoregionally advanced nasopharyngeal carcinoma: Induction chemotherapy counteracts the survival impact in high-risk patients defined by a novel model.
Li WJ, Su F, Ling LT … +14 more , Zhu BL, Deng B, Nong QQ, Yao Y, Zhou LQ, Cheng JW, Luo XW, Li Y, Guan Y, Li L, Qu S, Zhu XD, Bi M, Liang ZG
Transl Oncol · 2026 May · PMID 41825161 · Full text
PURPOSE: To develop a risk stratification model to identify high-risk locoregionally advanced nasopharyngeal carcinoma (NPC) susceptible to radiotherapy interruption (RTI) ≥5 days and evaluate whether induction chemother...
PURPOSE: To develop a risk stratification model to identify high-risk locoregionally advanced nasopharyngeal carcinoma (NPC) susceptible to radiotherapy interruption (RTI) ≥5 days and evaluate whether induction chemotherapy (IC) mitigated the associated survival detriment. METHODS: We retrospectively analyzed 820 patients treated with intensity-modulated radiotherapy, randomly allocated into training (n = 490) and validation (n = 330) cohorts. Prognostic factors for overall survival (OS) were screened using univariate and multivariate analyses. A Cox regression-based prognostic model was developed and evaluated via C-index and calibration plots. RTI ≥5 days impact on survival endpoints-OS, locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and failure-free survival (FFS)-was assessed across risk groups, with IC effect analyzed in high-risk patients using propensity score matching. RESULTS: A prognostic model incorporating age, T stage, N stage, and EBV-DNA >4000 copies/mL was established. The prognostic index (PI) stratified patients into high- and low-risk groups, with high-risk patients exhibiting significantly inferior survival in OS, DMFS, and FFS (all P < 0.05). The model demonstrated C-indices of 0.744 (training) and 0.658 (validation) for OS prediction, outperforming the 8th AJCC staging system. RTI ≥5 days significantly reduced OS in high-risk patients (training: HR 1.816, P = 0.034; validation: HR 2.310, P = 0.024) but not in low-risk patients. Importantly, IC ≥2 cycles eliminated RTI-associated survival differences in high-risk patients following confounding adjustment. CONCLUSION: The developed model effectively identified high-risk NPC patients vulnerable to RTI ≥5 days, with IC shown to mitigate this risk. These findings support the implementation of risk-stratified treatment strategies and proactive IC use to counter unavoidable treatment delays.
Molecular mechanisms and therapeutic targeting implications of ER/mTOR signaling axis-driven tumor progression in aggressive meningiomas.
Yao H, Zhu K, Li S … +7 more , Hei J, Wang S, Li W, Ye T, Jiang W, Martin T, Zhang S
Transl Oncol · 2026 Apr · PMID 41794007 · Full text
PURPOSE: Aggressive meningiomas pose substantial clinical challenges because of their high rates of recurrence. The aim of this study is to investigate the mechanistic role of estrogen receptor (ER)-mediated mTOR hyperac...
PURPOSE: Aggressive meningiomas pose substantial clinical challenges because of their high rates of recurrence. The aim of this study is to investigate the mechanistic role of estrogen receptor (ER)-mediated mTOR hyperactivation in promoting meningioma progression and to evaluate the therapeutic potential of targeting this signaling axis with tamoxifen. METHODS: Analyses involving data from clinical registries have established sex as a predictor of adverse outcomes, while multiomics investigations have revealed the overexpression of ER in advanced-grade and recurrent tumors. Functional validation was conducted using ER knockdown models. Mechanistic insights were obtained through RNA sequencing, with orthogonal validation performed via qPCR and Western blotting, with a focus on regulators of the mTOR pathway (RICTOR, PIK3CA, and DEPTOR). Therapeutic efficacy was evaluated in meningioma cell models through pharmacological inhibition using tamoxifen. RESULTS: Clinical analysis was used to identify sex as a predictor of adverse outcomes, revealing that ER overexpression is significantly correlated with advanced tumor grades. Silencing of the ER markedly reduced malignant phenotypes, leading to decreased cell proliferation and invasion, while also inducing apoptosis. Mechanistically, ER activation resulted in the upregulation of RICTOR and PIK3CA expression, alongside suppression of DEPTOR, which directly activated mTOR signaling. Tamoxifen exhibited potent antitumor effects by reversing this oncogenic signaling cascade. CONCLUSION: This study revealed that the ER/mTOR axis is associated with sex-linked therapeutic vulnerability in aggressive meningiomas. This finding provides mechanistic evidence for ER-driven mTOR activation via the dysregulation of RICTOR/PIK3CA-DEPTOR. The demonstrated efficacy of tamoxifen supports its clinical repurposing as a targeted therapy for ER-positive meningiomas, offering a biologically rational strategy to address therapeutic resistance in this challenging malignancy.
Development and characterization of anti-CXCR4 chimeric antigen receptor T cells.
Seir G, Bubb QR, Sotillo E … +3 more , Gruber T, Richards RM, Czechowicz A
Transl Oncol · 2026 Apr · PMID 41780186 · Full text
Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL) are aggressive hematologic malignancies characterized by dysregulation of normal hematopoiesis and acquisition of stem-like, self-renewing properties le...
Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL) are aggressive hematologic malignancies characterized by dysregulation of normal hematopoiesis and acquisition of stem-like, self-renewing properties leading to oncogenesis. Current treatments primarily rely on toxic chemotherapies with or without hematopoietic stem cell transplantation (HSCT). These are associated with significant short- and long-term side effects and sub-optimal outcomes across treatment of both AML and ALL. Improved HSCT methods are needed that can both eliminate leukemic cells and improve outcomes. The C-X-C chemokine receptor type 4 (CXCR4) plays a key role in both normal hematopoiesis and leukemogenesis by attracting and retaining cells in the bone marrow niche. It has been targeted using antibody or drug-based approaches leading to clinical trials and therapeutics across indications. In the context of chimeric antigen receptor (CAR) T cells, it has been expressed as a co-receptor to improve bone marrow homing and amplify tumor eradication. Here, we confirm high CXCR4 expression across AML and ALL using publicly available tumor transcriptomic datasets. Subsequently, we report the development of anti-CXCR4 CAR-T cells that demonstrate potent activity against a panel of leukemic cell lines in vitro without activity against other T cells. We observe decreased CXCR4 protein expression in CAR-positive populations indicating a potential pathway for T cell survival. Our findings support the potential of anti-CXCR4 CAR-T cells as a broadly applicable strategy for eliminating both AML and ALL, with possible extension to hematopoietic stem and progenitor cells, unlocking the potential of this strategy as a dual HSCT-conditioning and anti-leukemia agent.
Single-cell analysis of TIGD genes in hepatocellular carcinoma: Prognostic value and functional characterization.
Liu J, Chen X, Liu C … +2 more , Yang C, Li B
Transl Oncol · 2026 Apr · PMID 41775084 · Full text
BACKGROUND: Hepatocellular carcinoma (HCC) is an aggressive cancer with limited therapies. Although transposable element-derived genes are increasingly linked to tumorigenesis, the role of the TIGD family in HCC remains...
BACKGROUND: Hepatocellular carcinoma (HCC) is an aggressive cancer with limited therapies. Although transposable element-derived genes are increasingly linked to tumorigenesis, the role of the TIGD family in HCC remains unclear. This study examined the expression, clinical significance, and stemness-related features of TIGDs in HCC, emphasizing their prognostic and therapeutic potential. METHOD: TIGD expression was analyzed using TCGA data via GEPIA2, cBioPortal, and Kaplan-Meier Plotter, with protein validation from the Human Protein Atlas. Single-cell RNA-seq data (GSE242889) were used to examine TIGD expression across hepatic cell types. Survival and Cox regression analyses assessed prognostic value, while functional enrichment and immune infiltration analyses explored biological roles. TIGD5-high and TIGD5-low epithelial subsets were compared for functional features and cell-cell communication. RESULTS: TIGD1, 3, 4, 5, 6, and 7 were significantly upregulated in HCC. High TIGD4, TIGD5, and TIGD6 expression correlated with poorer overall survival and served as independent prognostic markers. TIGD5 exhibited the broadest and highest expression across immune and stromal compartments. Stratification of epithelial cells into TIGD5-high and TIGD5-low subsets revealed distinct functional phenotypes: TIGD5-high cells showed enrichment in extracellular matrix organization, growth factor signaling, and immune regulatory pathways, with enhanced communication probability within the tumor microenvironment. Notably, TIGD5+ epithelial cells demonstrated increased interaction strength and MIF signaling pathway engagement compared to TIGD5- counterparts. Functional analyses indicated roles in RNA splicing, DNA replication, and cell-cycle regulation. TIGDs also showed associations with immune infiltration, particularly Th2 cells. CONCLUSION: TIGD4, TIGD5, and TIGD6 exhibit oncogenic potential and may serve as prognostic biomarkers and therapeutic targets in HCC. Their stem-cell-associated expression highlights a novel connection between transposable element-derived genes and liver cancer stemness.
Sohlh2 inhibited the angiogenesis of hepatocellular carcinoma through the HIF-1α/VEGFA pathway.
Liu Q, Zhang Y, Wu Y … +2 more , Chen S, Wang J
Transl Oncol · 2026 Apr · PMID 41775083 · Full text
PURPOSE: To investigate the role of Sohlh2 in hepatocellular carcinoma (HCC) and its potential mechanisms. METHODS: This study focused on Hep3B and HepG2 cells and employed lentiviral transfection to create Sohlh2 overex...
PURPOSE: To investigate the role of Sohlh2 in hepatocellular carcinoma (HCC) and its potential mechanisms. METHODS: This study focused on Hep3B and HepG2 cells and employed lentiviral transfection to create Sohlh2 overexpression and knockdown models. Through CCK8, flow cytometry, angiogenesis and immunofluorescence experiments, the effects of Sohlh2 on tumor cell proliferation, cell cycle progression, apoptosis, and angiogenesis were investigated. Additionally, its regulatory role in the HIF-1α/VEGFA pathway was explored. The experiments were repeated after introducing the Sohlh2 agonist CoCl and antagonist LW6. Additionally, a Hep3B tumor-bearing mouse model was established to evaluate the effect of Sohlh2 on liver cancer growth. RESULT: Experimental results indicated that Sohlh2 was highly expressed in normal human hepatocytes but was downregulated in HCC cells. Overexpression of Sohlh2 inhibited HCC cell proliferation by blocking the transition from the G0/G1 phase to the S phase, promoted apoptosis, suppressed the expression of HIF-1α and CD31, and consequently inhibited tumor angiogenesis. Conversely, downregulation produced the opposite effects. In vivo and in vitro mechanistic studies indicated that HIF-1α agonists reversed the anti-proliferative, pro-apoptotic, and anti-angiogenic effects induced by Sohlh2 overexpression in HCC. Conversely, the antagonist LW6 significantly mitigated the effects of Sohlh2 knockdown. CONCLUSION: Our research suggested that that Sohlh2 exerted a tumor-suppressing gene function in hepatocellular carcinoma by inhibiting the HIF-1α/VEGFA signaling pathway. These findings provided a potential molecular target for the development of anti-angiogenic therapies in HCC.
The Hippo pathway in clear cell renal cell carcinoma (ccRCC): a nexus with the VHL disruption?
Waeckel T, Lefranc R, Waeckel M … +4 more , Riffet M, Tillou X, Levallet G, Bazille C
Transl Oncol · 2026 Apr · PMID 41764979 · Full text
BACKGROUND: Clear cell renal cell carcinoma (ccRCC) represents 70% of kidney cancers, with 20-50% recurrence risk after surgery. Despite therapeutic advances, no reliable biomarkers have been identified for patient strat...
BACKGROUND: Clear cell renal cell carcinoma (ccRCC) represents 70% of kidney cancers, with 20-50% recurrence risk after surgery. Despite therapeutic advances, no reliable biomarkers have been identified for patient stratification or treatment response prediction. While VHL gene alterations are well-established in ccRCC pathogenesis, the role of the Hippo pathway remains underexplored despite ample evidence of its involvement. OBJECTIVE: This review synthesizes current knowledge on Hippo pathway alterations in ccRCC and examines its crosstalk with the VHL/HIF axis, identifying potential biomarkers and therapeutic targets. STRATEGY: We comprehensively analyzed literature on Hippo pathway components in ccRCC, focusing on molecular mechanisms, clinical correlations, and interactions with VHL signaling. RESULTS: Multiple Hippo pathway alterations characterize ccRCC: RASSF1A hypermethylation, NF2 mutations (particularly in aggressive variants), SAV1 downregulation associated with 14q loss, and LATS1/2 methylation-mediated inactivation. These changes result in YAP/TAZ nuclear accumulation and oncogenic transcription. Importantly, chromosome 3p loss simultaneously disrupts both VHL and RASSF1, creating a unique double-hit scenario. The VHL-Hippo crosstalk operates through multiple mechanisms: HIF-induced GPRC5A and VEGFR signaling inhibit LATS1/2 phosphorylation, promoting YAP/TAZ activation, while active YAP/TAZ enhances pro-angiogenic gene transcription, amplifying hypoxic responses. Low expression of RASSF1A, SAV1, and LATS1/2, coupled with high YAP/TAZ activity, correlates with advanced tumor stage, higher grade, and poorer survival. CONCLUSIONS: The Hippo pathway represents a critical yet underappreciated dimension of ccRCC biology, offering promising biomarkers for risk stratification and novel therapeutic targets. The Hippo-VHL nexus presents multiple intervention points that could enhance current treatment.
Dissecting incidence and mortality inequalities of six types of liver diseases in 39 alcohol-dominant countries and 93 virus-dominant countries under the aging context: Insights from the Global Burden of Disease Study 2021.
Meng N, Chen Y, Zhai C … +5 more , Sun H, Wang Y, Zhao D, Wang F, Zou Y
Transl Oncol · 2026 Apr · PMID 41763069 · Full text
BACKGROUND: Chronic liver disease (CLD) and liver cancer (LC) pose significant global health challenges affecting millions of people worldwide. An etiology-region-time specific understanding of their global burden is nec...
BACKGROUND: Chronic liver disease (CLD) and liver cancer (LC) pose significant global health challenges affecting millions of people worldwide. An etiology-region-time specific understanding of their global burden is necessary. METHODS: This study utilized data from the 2021 Global Burden of Disease Study, encompassing incidence, prevalence, mortality, and Disability-Adjusted Life Years (DALYs) attributed to CLD and LC. RESULTS: In 2021, global deaths from CLD and LC were 1,425 thousand and 483 thousand, respectively, with a decline in age-standardized death rates (ASDR) by 31.9% and 3.7% from 1990 to 2021. By categorizing the 21 regions into alcohol-dominant (Region A, 39 countries), HBV-dominant (Region B, 60 countries), and HCV-dominant (Region C, 33 countries), distinct health inequities emerged. In Region A, Romania and Ukraine face rising incidence and mortality rates due to alcohol-induced liver disease. In Region B, HBV-related rates are high in Nigeria and Mali, while China has reduced. Region C, including the Central African Republic and Libya, shows high HCV-induced rates, highlighting regional disparities. The incidence and mortality rates of CLD are negatively correlated with the Human Development Index (HDI), with varying regional trends. In Region A, health inequities have narrowed, while they have intensified in Regions B and C. Significant health inequities exist, with CB and CC burdens more concentrated in high-HDI countries where inequities are diminishing, whereas CA burdens are predominantly in low-HDI countries, where inequities are more pronounced. CONCLUSION: These findings highlight the urgent need to address health inequities in liver disease burden across specific regions.
A2AR as a key target for immune microenvironment remodeling in prostate cancer.
Yan L, Yang Z, Zhao X … +2 more , Chen Y, Wang Z
Transl Oncol · 2026 Apr · PMID 41763068 · Full text
This study elucidates the critical role of adenosine A2A receptor (A2AR) signaling in prostate cancer progression through comprehensive molecular characterization and clinical validation, demonstrating that A2AR overexpr...
This study elucidates the critical role of adenosine A2A receptor (A2AR) signaling in prostate cancer progression through comprehensive molecular characterization and clinical validation, demonstrating that A2AR overexpression in prostate cancer cells drives profound immunosuppression via coordinated upregulation of CD73-mediated adenosine production, subsequent activation of immunosuppressive pathways including ARG1, TGF-β, and IL-10 secretion, and induction of immune checkpoint molecules PD-L1 and Galectin-9, which collectively promote myeloid-derived suppressor cell expansion and CD8 T cell exhaustion while creating an immunologically privileged tumor microenvironment. Clinical correlation analyses across multiple patient cohorts reveal that elevated A2AR expression serves as a powerful independent predictor of aggressive disease progression and poor clinical outcomes, particularly in metastatic castration-resistant prostate cancer, where it exhibits stronger prognostic value than in other solid tumors. A2AR activation not only helps tumors resist immune checkpoint inhibitors but also blocking A2AR can work well with PD-1/PD-L1 treatments by reversing the immune suppression caused by adenosine and boosting the body's ability to fight tumors. The potential for using these findings in real-world clinical settings is backed by models showing that combining A2AR expression with adenosine pathway activity and immune profiling greatly improves the accuracy of risk assessment compared to standard prognostic markers, while earlier studies show that targeting this pathway could be a viable treatment option. These results collectively position A2AR as a master regulator of prostate cancer immunosuppression and a promising biomarker-guided therapeutic target, particularly for combination immunotherapy approaches in advanced disease settings where current treatment options remain limited.
Markers of immune activation and immunotherapy responsiveness are increased in 3D Pancreatic cancer organoids when primed with photodynamic- and chemo-therapy.
Cabral FV, Quilez-Alburquerque J, Szoo MJ … +3 more , de Silva P, Saad MA, Hasan T
Transl Oncol · 2026 Apr · PMID 41762540 · Full text
Pancreatic ductal adenocarcinoma (PDAC) remains highly resistant to chemotherapy and immunotherapy due to a dense tumor stroma and an immunosuppressive tumor microenvironment. In this study, we explored whether the photo...
Pancreatic ductal adenocarcinoma (PDAC) remains highly resistant to chemotherapy and immunotherapy due to a dense tumor stroma and an immunosuppressive tumor microenvironment. In this study, we explored whether the photodynamic priming (PDP) effect, a fallout of Photodynamic therapy (PDT), an approved treatment, could improve the treatment responses in 3D mouse-derived organoids. The organoids reproduced key features of pancreatic tumors and showed strong resistance to chemotherapy (nanoliposomal irinotecan, nal-IRI) and immune checkpoint inhibitor (anti-PD-1) when used alone. PDP overcame this resistance by enhancing the uptake and activation of nal-IRI, thereby increasing tumor cell death. PDP also triggered immunogenic cell death, marked by the release of danger signals that promote immune activation. When organoids were co-cultured with autologous peripheral blood mononuclear cells (PBMCs), PDP enhanced immune-mediated tumor killing. Notably, combining PDP with low doses of chemotherapy and PD-1 blockade resulted in complete tumor eradication. These effects were associated with increased immune activation and improved responsiveness to immunotherapy. Together, these findings show that PDP remodels the pancreatic tumor microenvironment, enhances chemotherapy efficacy, and sensitizes tumors to immune checkpoint inhibitors. This strategy uses clinically approved agents and offers a promising, translatable approach to overcoming treatment resistance in pancreatic cancer.
Construction and validation of golgi apparatus-related genes as predictors of the immune microenvironment and prognosis in colorectal cancer.
Chen J, Wang F
Transl Oncol · 2026 Apr · PMID 41762539 · Full text
BACKGROUND: Colorectal cancer (CRC) is the third most common cancer globally, and the identification of novel biomarkers remains an urgent priority in clinical practice and research. Although the Golgi apparatus plays a...
BACKGROUND: Colorectal cancer (CRC) is the third most common cancer globally, and the identification of novel biomarkers remains an urgent priority in clinical practice and research. Although the Golgi apparatus plays a crucial role in tumorigenesis and cancer progression, its role in CRC remains unclear. METHODS: A comprehensive bioinformatics analysis of the transcriptome was conducted using the TCGA and GSE87211 datasets. A reliable risk signature model based on Golgi apparatus - related genes (GARGs) was constructed. Subsequently, we performed an in - depth single - cell RNA sequencing analysis. Finally, based on the consistent evidence across all analytical layers, GDI1 was selected for subsequent functional validation in cellular assays. RESULTS: By integrating univariate Cox regression and LASSO analysis, we identified a five-GARG signature to construct a prognostic model. This model stratified patients into high- and low-risk groups with significantly different overall survival. The high-risk group was associated with elevated stromal and ESTIMATE scores, along with increased infiltration of monocytes and M0 macrophages, suggesting a potentially more immunosuppressive and tumor-promoting microenvironment. Bioinformatic predictions indicated that the high-risk group might show enhanced sensitivity to Dasatinib, Sapitinib, and SB216763; this was preliminarily supported by our subsequent in vitro drug sensitivity assays. Cell-cell communication analysis suggested that macrophages might primarily influence the microenvironment through the tumor necrosis factor (TNF) signaling pathway. Critically, functional experiments demonstrated that silencing GDI1 significantly inhibited cell proliferation and migration and induced apoptosis, supporting its potential oncogenic role in COAD. CONCLUSION: Collectively, our work links GARG expression to CRC prognosis and immune features, and functionally implicates GDI1 in tumor cell aggressiveness, supporting its further study as a potential therapeutic target.
From prostate specific antigen to genomic signatures: Advances in biomarkers for prostate cancer diagnosis and prognosis.
Hamed NW, Elbeljihy HS, Hussin SA … +3 more , Fouda RM, Oy EK, W Magar R
Transl Oncol · 2026 Apr · PMID 41762538 · Full text
Prostate cancer is one of the most prevalent malignancies affecting men worldwide. It arises from the uncontrolled proliferation of abnormal cells within the prostate gland, an essential component of the male reproductiv...
Prostate cancer is one of the most prevalent malignancies affecting men worldwide. It arises from the uncontrolled proliferation of abnormal cells within the prostate gland, an essential component of the male reproductive system, and exhibits highly variable clinical behaviour, ranging from indolent, localised tumours to aggressive, metastatic disease. Early detection significantly improves treatment outcomes and survival rates, emphasising the urgent need for more sensitive and specific diagnostic approaches. This review provides a comprehensive overview of diagnostic and prognostic biomarkers associated with prostate cancer, highlighting their potential in early detection and disease monitoring. Traditional biomarkers such as digital rectal examination (DRE), prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), and alkaline phosphatase (ALP) are discussed alongside emerging molecular markers that offer enhanced accuracy and predictive value. These include PCA3, SelectMDx, ExoDx Prostate (EPI), bone-specific ALP (BALP), 4Kscore, circulating tumour cells (CTCs), prostate health index (PHI), Oncotype DX Genomic Prostate Score (GPS), Decipher test, and ERG gene fusion. Additionally, the review addresses key genetic alterations implicated in prostate carcinogenesis, including mutations in BRCA1/2, HOXB13, and PTEN deletions, as well as changes in the androgen receptor pathway. By evaluating recent advancements and applications of these biomarkers, this review aims to enhance understanding of their role in improving early diagnosis, prognosis, and personalised management of prostate cancer.
Molecular epidemiology of the expression of urokinase plasminogen activator receptor-associated protein (uPARAP) in mesenchymal malignancies.
Wang CC, Barkholt P, Wozniak A … +9 more , Vanleeuw U, Lee CJ, De Sutter L, De Cock L, Verbeeck K, Engelholm LH, Lynch C, Mumberg D, Schöffski P
Transl Oncol · 2026 Apr · PMID 41734474 · Full text
INTRODUCTION: Sarcomas are highly heterogenous and rare malignant tumors derived from mesenchymal cells. The current standard treatments for advanced disease have low response rates and are typically associated with cons...
INTRODUCTION: Sarcomas are highly heterogenous and rare malignant tumors derived from mesenchymal cells. The current standard treatments for advanced disease have low response rates and are typically associated with considerable toxicity. The aim of this study was to investigate the expression of a potential novel therapeutic target and its clinical correlation in sarcomas, namely urokinase plasminogen activator receptor-associated protein (uPARAP/Endo180/CD280). MATERIALS AND METHODS: We evaluated uPARAP expression in various sarcoma subtypes and in normal tissues using 12 tissue microarrays. Expression was assessed on immunohistochemically stained slides and scored according to staining intensity and the percentage of positive tumor cells. Clinical correlations between uPARAP expression and selected parameters (gender and sample origin) were analyzed using generalized estimating equations, and survival outcomes were evaluated with Kaplan-Meier and log-rank tests. RESULTS: Our results demonstrated limited uPARAP expression in normal tissues, while high expression was observed in the majority of analyzed sarcoma subtypes, particularly high (>80% of highly positive cases) in fibrosarcoma, synovial sarcoma, undifferentiated pleomorphic sarcoma, malignant peripheral nerve sheath tumor, and various bone sarcomas. Based on the correlation analyses between uPARAP expression and selected clinical parameters or survival outcomes, most subtypes did not show a statistically significant association. CONCLUSION: In conclusion, this study highlights the potential of uPARAP as an innovative target for targeted treatments, such as novel antibody-drug conjugates in sarcoma.
Lactylation profiling reveals novel biomarkers and immune interactions in pancreatic cancer.
Xu D, Chen Q, Wang L … +4 more , Li L, Cheng K, Liu X, Lin K
Transl Oncol · 2026 Apr · PMID 41734473 · Full text
Pancreatic cancer, known for its aggressive nature and poor prognosis, often eludes early detection and effective treatment. This study investigates the underexplored terrain of protein lactylation in pancreatic cancer t...
Pancreatic cancer, known for its aggressive nature and poor prognosis, often eludes early detection and effective treatment. This study investigates the underexplored terrain of protein lactylation in pancreatic cancer to identify potential biomarkers and understand its immunological implications. Proteomic and transcriptomic analyses were conducted to profile lactylation changes, identifying 11 upregulated and 1 downregulated lactylation-related proteins. Intersection analysis between proteomics and transcriptomics highlighted four key genes (COQ9, GAA, LYST and TP53) with consistent expression trends, suggesting their central role in the lactylation pathway within pancreatic cancer. ROC curve analysis underscored the diagnostic potential of GAA and LYST, with AUCs over 0.9. Further, ssGSEA revealed significant correlations between these core genes and various immune cells, indicating an immune-modulatory role. Notably, most core lactylation-related genes were positively associated with immune checkpoint molecules, barring COQ9. GSEA of gene expression groups delineated three conserved upregulated KEGG pathways, with additional REACTOME pathway analysis uncovering 68 conserved pathways. These findings highlight lactylation's involvement in pancreatic cancer progression and its possible exploitation for diagnostic and therapeutic advancements.
Somatic mutations in cervicovaginal samples: assessing their role in ovarian cancer detection and prognosis.
Pelegrina B, Paytubi S, Benavente Y … +18 more , Marin F, López-Querol M, Onieva I, Frias-Gomez J, Pavon-Diaz C, Martínez JM, Fernandez-Gonzalez S, Dorca E, Vidal A, Barahona M, Pérez-Escanilla Y, Brunet J, Pineda M, Pijuan L, Ponce J, Matias-Guiu X, Alemany L, Costas L
Transl Oncol · 2026 Apr · PMID 41734472 · Full text
BACKGROUND: Most patients with ovarian cancer are diagnosed at a late stage because of the lack of early stage symptoms or effective screening methods. To address this issue, we evaluated the presence of DNA somatic vari...
BACKGROUND: Most patients with ovarian cancer are diagnosed at a late stage because of the lack of early stage symptoms or effective screening methods. To address this issue, we evaluated the presence of DNA somatic variants in cervicovaginal samples to aid the detection and prognosis of ovarian cancer. METHODS: We employed next-generation sequencing (NGS) with molecular identifiers to analyze samples from a case-control study involving women diagnosed with ovarian cancer and age-matched controls. The study included Pap smear samples from 43 patients with ovarian cancer and 99 controls, 27 paired vaginal self-samples, 16 endometrial aspirates, and 13 tumor samples from cases, for a total of 198 samples. RESULTS: Pathogenic and likely pathogenic variants were identified in 25.6 % (11/43, 95 % confidence interval -CI-:13.5-41.2) of Pap smear samples from patients with ovarian cancer. These variants were also found in 33.3 % of the control samples, leading to a specificity of 66.7 % (66/99, 95 %CI:56.5-75.8 %). Among the paired samples, we observed pathogenic and likely pathogenic variants in 14.3 % (2/14, 95 %CI:1.78-42.8) of the vaginal samples, 77.8 % (7/9, 95 %CI:40.0-97.2) of the endometrial aspirates, and 69.2 % (9/13, 95 %CI:39.6-90.9) of the tumor samples. In the age- and stage-adjusted survival models, women with variants detected in Pap smear samples had poorer overall survival than those without variants (hazard ratio -HR-=4.27, 95 %CI:1.06-17.23; P = 0.041). CONCLUSIONS: DNA somatic variants in cervicovaginal samples have limited diagnostic value for detecting ovarian cancer. However, their presence may have prognostic significance, warranting further investigation. Future research could explore multimodal strategies that integrate molecular markers with imaging or other approaches to improve early detection.
Cystic lesions and their role in pancreatic cancer risk stratification.
Lyons R, Maher SG, Lysaght J
Transl Oncol · 2026 Apr · PMID 41724074 · Full text
The prognosis for patients diagnosed with pancreatic cancer has changed little over the past 4 decades. Fewer than 20 % of patients are diagnosed at a stage amenable to potentially curative surgery and therapeutic resist...
The prognosis for patients diagnosed with pancreatic cancer has changed little over the past 4 decades. Fewer than 20 % of patients are diagnosed at a stage amenable to potentially curative surgery and therapeutic resistance remains widespread, compounded by a lack of therapeutic targets. Early detection of pancreatic cancer is notoriously difficult, due to non-specific symptoms that delay early diagnosis in addition to limited sensitivity of current imaging modalities. However, pancreatic cystic lesions (PCLs), such as intraductal papillary mucinous neoplasms (IPMNs), provide a unique opportunity for earlier disease intervention. Indeed, PCLs can be stratified by risk of malignant transformation, but current stratification guidelines remain highly contended within the field. Importantly, accumulating evidence suggests that inflammatory and immunogenetic mechanisms may influence both cyst development and malignant progression, yet these immunobiological factors are not currently integrated into PCL risk-stratification and management frameworks. In this review, we focus on the immunobiological dimension of PCLs, highlighting the interplay between chronic inflammation, immune dysregulation, and genetic alterations that may drive cystogenesis and malignant transformation. Furthermore, we assess the evidence to support integrating an immunobiological aspect to existing risk stratification guidelines to enhance identification of high-risk pre-malignant PCLs. Such integration may ultimately identify high-risk patients more accurately and inform surveillance and therapeutic intervention strategies to prevent late-stage pancreatic cancer.
SELE is associated with reduced breast cancer susceptibility: Evidence from Mendelian randomization and single-cell transcriptome.
Chen H, Hu W, Liu R … +2 more , Liu Q, Cheng X
Transl Oncol · 2026 Apr · PMID 41722201 · Full text
BACKGROUND: The role of circulating proteins in breast cancer (BC) early diagnosis remains unclear. We investigated genetically predicted associations between circulating proteins and BC risk using Mendelian randomizatio...
BACKGROUND: The role of circulating proteins in breast cancer (BC) early diagnosis remains unclear. We investigated genetically predicted associations between circulating proteins and BC risk using Mendelian randomization (MR). This study aims to identify novel protein biomarkers through an integrative multi-omics approach. METHODS: Using a two-sample MR framework, we assessed genetically determined circulating protein associations with BC risk/subtypes. Analysis incorporated large-scale protein quantitative trait loci (pQTL) and genome-wide association studies (GWAS) data, strengthened by cross-validation, sensitivity analyses (MR-Egger, MR-PRESSO), and meta-analysis. We further performed genetic colocalization, molecular docking, and phenome-wide MR (PheWAS-MR). Bulk and single-cell RNA sequencing data were analyzed to compare gene expression of causal proteins between healthy and BC tissues. This multi-layered validation enhances the robustness of causal inference. RESULTS: Three circulating proteins are associated with reduced BC risk-SELE (OR = 0.98, 95 % CI: 0.97-0.98), CDH1 (OR = 0.94, 95 % CI: 0.93-0.95), ALPI (OR = 0.95, 95 % CI: 0.94-0.96). CNTNAP2 is associated with elevated BC risk (OR = 1.02, 95 % CI: 1.01-1.03). Colocalization supported shared causal variants for SELE and ALPI. Molecular docking simulation indicates high binding affinity of SELE-simvastatin. SELE expression was significantly reduced in endothelial cells of BC tissue, and PheWAS-MR revealed SELE's association with 123 phenotypes, highlighting its extensive pleiotropic effects. CONCLUSIONS: This study provides robust genetic evidence for the causal roles of SELE, CDH1, and ALPI in reducing BC risk. The integrative proteomic-genetic-transcriptomic approach identifies potential therapeutic targets and offers new insights into BC pathogenesis, presenting hypotheses for clinical validation.
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