Neoplasia最新文献

{"title":"Metabolic and imaging phenotypes associated with RB1 and TP53 loss in prostate cancer","authors":"Fahim Ahmad ,&nbsp;Margaret White ,&nbsp;Kazutoshi Yamamoto ,&nbsp;Daniel R. Crooks ,&nbsp;Supreet Agarwal ,&nbsp;Ye Yang ,&nbsp;Brian Capaldo ,&nbsp;Sonam Raj ,&nbsp;Aian Neil Alilin ,&nbsp;Anita Ton ,&nbsp;Stephen Adler ,&nbsp;Jurgen Seidel ,&nbsp;Colleen Olkowski ,&nbsp;Murali Krishna Cherukuri ,&nbsp;Peter L Choyke ,&nbsp;Kathleen Kelly ,&nbsp;Jeffrey R. Brender","doi":"10.1016/j.neo.2025.101235","DOIUrl":"10.1016/j.neo.2025.101235","url":null,"abstract":"<div><div>Advanced prostate cancer is treated with androgen receptor (AR) signaling inhibitors, which are initially effective, but most patients eventually develop resistance and progress to castrate-resistant prostate cancer (CRPC). Loss of RB1 in CRPC tumors is correlated with rapid progression and poor patient survival and, in combination with TP53 loss, predisposes patients to the development of transitional neuroendocrine prostate cancer (NEPC). Although progressive CRPC is clinically associated with higher 18FDG-PET SUVmax values, it is unknown whether inactivation of RB1 and/or TP53 is a driver of increased glucose import. Using a cohort of patient-derived xenograft (PDX)-derived CRPC organoids, we found that NEPC could not be conclusively distinguished from adenocarcinoma by 18FDG uptake alone, and PSMA protein levels did not correlate with cancer phenotype or 18FDG uptake. Castration-resistant models showed higher 18FDG uptake, but lower pyruvate-to-lactate conversion compared to their castration-sensitive counterparts. In parallel studies using castration-sensitive prostate cancer models, RB1/TP53 knockdown did not affect 18FDG uptake, but increased basal respiration and glycolytic activity, with combined depletion leading to glucose diversion into glycogenesis. These metabolic changes were reflected in increased lactate dehydrogenase flux detected by 13C-hyperpolarized magnetic resonance spectroscopy upon RB1 loss, but not in 18FDG uptake. The metabolic heterogeneity revealed here suggests that a multimodal molecular imaging approach can improve tumor characterization, potentially leading to a better prognosis in cancer treatment.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"70 ","pages":"Article 101235"},"PeriodicalIF":7.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145253296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age-diet interactions significantly influence intratumoral gene expression, gut microbiome signature and tumor microenvironment in colorectal cancer","authors":"Shivani Soni ,&nbsp;Pooja Mittal ,&nbsp;Jae Ho Lo ,&nbsp;Yan Yang ,&nbsp;Goar Smbatyan ,&nbsp;Keehoon Lee ,&nbsp;Junxiang Wan ,&nbsp;Hiroshi Kumagai ,&nbsp;Kelvin Yen ,&nbsp;Hemal H. Mehta ,&nbsp;Brendan Miller ,&nbsp;Lesly Torres-Gonzalez ,&nbsp;Francesca Battaglin ,&nbsp;Unnati Hemant Shah ,&nbsp;Michela Bartolini ,&nbsp;Wu Zhang ,&nbsp;David W. Craig ,&nbsp;Josh Millstein ,&nbsp;Pinchas Cohen ,&nbsp;Heinz-Josef Lenz","doi":"10.1016/j.neo.2025.101245","DOIUrl":"10.1016/j.neo.2025.101245","url":null,"abstract":"<div><div>Colorectal Cancer (CRC) is the third most prevalent malignancy, leading to significant morbidity and mortality globally. Epidemiological studies suggest that chronological age and diet are among the major contributing factors correlated with the incidence of CRC. Our study aimed to provide insights into the association between age, diet, and gut microbiome in CRC using molecular techniques including RNA sequencing, cytokine analysis, and metagenomic analysis. We used syngeneic MC38 mice model divided into two age groups (old and young) and three diet groups (standard chow, calorie-restricted and high-fat). The major findings of this study are that age and diet impact intratumoral gene signaling (nuclear and mitochondrial), and hub genes we identified are associated with prognosis in CRC. Fecal microbiome analysis showed that old microbiomes have higher alpha diversity compared to young mice. Our results demonstrate that interactions between host (age) and external (diet) factors regulate tumor growth mediated by cytokines, mitochondrial derived proteins, and the gut microbiome. Collectively, our findings advance current understanding of the mechanisms by which aging, diet and gut microbiota impact CRC onset and progression though further investigation is warranted.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"70 ","pages":"Article 101245"},"PeriodicalIF":7.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145363830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Wnt/β-catenin signaling enhances the efficacy of anti-CD38 immunotherapy in multiple myeloma","authors":"Heng Li ,&nbsp;Yunguang Chen ,&nbsp;Michaela Gregorova ,&nbsp;Tingting Yang ,&nbsp;Xiayi Zhang ,&nbsp;Xiaoyu Yu ,&nbsp;Zhen Wang ,&nbsp;Haiying Hua ,&nbsp;Long Ye ,&nbsp;Xiaowei Qi ,&nbsp;Marcel Spaargaren ,&nbsp;Steven T. Pals ,&nbsp;Zemin Ren","doi":"10.1016/j.neo.2025.101242","DOIUrl":"10.1016/j.neo.2025.101242","url":null,"abstract":"<div><h3>Background</h3><div>Previous studies have shown that the Wnt/β-catenin signaling pathway is aberrantly activated in multiple myeloma (MM) and regulates the growth of MM cells, while recent studies reported crosstalk between Wnt and STAT3 signaling in various non-MM systems. In addition, it has been shown that STAT3 regulates the expression of CD38, the key target of current antibody therapies in MM. Therefore, we aimed to investigate the impact of inhibiting the Wnt signaling on the efficacy of anti-CD38 immunotherapy.</div></div><div><h3>Methods</h3><div>We utilized dnTCF overexpression and β-catenin knockout to inhibit the Wnt signaling. Flow cytometry was used to analyze the expression of CD38. NK92MI-CD16 and CB-derived NK cells were used to conduct ADCC in cell lines and patient-derived MM. A xenograft mouse model was used to evaluate the therapeutic efficacy of inhibiting Wnt signaling in combination with daratumumab <em>in vivo</em>.</div></div><div><h3>Results</h3><div>We demonstrate that inhibition of Wnt signaling results in reduced STAT3 activity in both MM cell lines and primary MM samples. The suppression of STAT3 activity by Wnt signaling inhibition significantly enhances the expression of CD38, which is a crucial determinant of the clinical response to anti-CD38 treatment, viz. daratumumab. In accordance, targeting of Wnt signaling with the Wnt inhibitor ICG-001 greatly enhanced the anti-MM efficacy of daratumumab <em>in vitro</em> as well as in an <em>in vivo</em> mouse model.</div></div><div><h3>Conclusions</h3><div>These findings demonstrated that targeting Wnt signaling enhances the efficacy of daratumumab and provide a strong rationale for combining daratumumab with Wnt-signaling inhibition as a therapeutic strategy in MM.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"70 ","pages":"Article 101242"},"PeriodicalIF":7.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145363835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RANKL and CSF-1 are elevated in periovulatory follicular fluid of BRCA1 mutation carriers and increase proinflammatory signaling in fallopian tube epithelial cells","authors":"Alexandra Kollara ,&nbsp;Vidushi Madaan ,&nbsp;Jianhong Zhang ,&nbsp;Ellen M. Greenblatt ,&nbsp;Theodore J. Brown","doi":"10.1016/j.neo.2025.101237","DOIUrl":"10.1016/j.neo.2025.101237","url":null,"abstract":"<div><div>Pathogenic germline mutations in <em>BRCA1</em> predispose individuals to high-grade serous tubo-ovarian cancer (HGSTOC), which originates in the fallopian tube epithelium (FTE). Identified non-genetic risk factors are consistent with a potential role for repetitive exposure of FTE cells to follicular fluid during ovulation in the development of this disease. We previously showed that BRCA1 deficiency in non-malignant FTE cells associates with increased proinflammatory NFκB signaling, which could contribute to the development of HGSTOC. Additionally, exposure of <em>BRCA1</em> mutated primary FTE cells to periovulatory follicular fluid resulted in further increased levels of proinflammatory gene transcripts as compared to cells isolated from control patients. In this study, we compared cytokine levels in periovulatory follicular fluid collected from <em>BRCA1</em> mutation carriers to that of non-<em>BRCA1</em> mutation carriers. Follicular fluid was collected from 59 patients diagnosed with breast cancer undergoing controlled ovarian stimulation and oocyte retrieval as part of their oncofertility treatment. Samples included 13 patients with confirmed <em>BRCA1</em> mutations, 15 patients with mutations in other susceptibility genes and 31 patients confirmed as non-<em>BRCA1</em> mutation carriers. Levels of 92 inflammatory proteins were measured using an antibody array with a proximity extension assay. Partial Least-Squares Discriminant Analysis indicated that samples from <em>BRCA1</em> mutation carriers clustered separately from other samples, indicating <em>BRCA1</em> mutation status influences cytokine levels in follicular fluid. RANKL and CSF-1 were among 7 proteins found to be statistically elevated in follicular fluid from <em>BRCA1</em> mutation carriers. Treatment of an immortalized FTE cell line with RANKL and CSF-1 increased NFκB signaling and levels of proteins encoded by type I interferon-stimulated genes. These findings support further investigation exploring the potential of targeting RANKL and CSF-1 for HGSTOC prevention strategies in <em>BRCA1</em> mutation carriers.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"70 ","pages":"Article 101237"},"PeriodicalIF":7.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145259703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adverse prognosis of GM-CSF expression in human cutaneous melanoma","authors":"Elena García-Martínez ,&nbsp;Alicia Nieto-Valle ,&nbsp;Celia Barrio-Alonso ,&nbsp;Baltasar López-Navarro ,&nbsp;José Antonio Avilés-Izquierdo ,&nbsp;Verónica Parra-Blanco ,&nbsp;Alba Gutiérrez-Seijo ,&nbsp;Paloma Sánchez-Mateos ,&nbsp;Rafael Samaniego","doi":"10.1016/j.neo.2025.101240","DOIUrl":"10.1016/j.neo.2025.101240","url":null,"abstract":"<div><h3>Background</h3><div>GM-CSF, a myeloid-priming cytokine, exhibits context-dependent effects on tumor growth and, despite its clinical use, its role in human melanoma remains undefined.</div></div><div><h3>Methods</h3><div>A stage II-IV primary melanoma cohort (<em>n</em> = 80) was interrogated for GM-CSF/GM-CSFR expression at the single-cell level in tumor-associated macrophages (TAMs) and tumor cells (TCs). Invasion, survival and lung colonization assays were used to determine the pro-tumoral role of GM-CSF, and RNA-seq to analyze transcriptomic profiles.</div></div><div><h3>Results</h3><div>GM-CSF was significantly enriched in TAMs and TCs of primary cutaneous melanoma samples from patients who subsequently developed metastasis, compared with non-metastasizing ones, correlating with reduced disease-free and overall survival (<em>p</em> &lt; 0.0001). GM-CSF receptor subunits were present in both cell types and their expression did not correlate with clinical outcomes. GM-CSF activated non-canonical signaling pathways in TCs, promoted their invasiveness and enhanced in vivo lung colonization in a murine model. GM-CSF–primed macrophages secreted higher levels of inflammatory cytokines upon interaction with melanoma cells than those unprimed or primed with M-CSF. Reciprocally, RNA-seq analyses revealed a broader transcriptional reprogramming in melanoma cells exposed to GM-CSF-primed macrophages.</div></div><div><h3>Conclusions</h3><div>Our findings highlight a potentially pro-tumorigenic GM-CSF-driven paracrine axis in patients with poor-prognosis melanoma, supporting therapeutic strategies aimed at disrupting this signaling network.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"70 ","pages":"Article 101240"},"PeriodicalIF":7.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145318647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Steatohepatitis alters lymphocytes cytotoxicity and localization, accelerating colorectal liver metastases","authors":"Adi S. Yehezkel ,&nbsp;Eyal Yehezkel ,&nbsp;Nathalie Abudi ,&nbsp;Rinat Abramovitch","doi":"10.1016/j.neo.2025.101222","DOIUrl":"10.1016/j.neo.2025.101222","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>The liver is the most common site for distant metastasis. Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most common liver disease worldwide and significantly increases the risk of liver metastasis in colorectal cancer (CRC) patients. We aimed to elucidate hepatic immune cells alterations in response to the metabolic stress in MAFLD and their influence on the early stages of CRC liver metastasis (CRLM).</div></div><div><h3>Methods</h3><div>High-fat diet (HFD) and Western diet (WD), were used to create MAFLD and MASH respectively. MC38 cancer cells were injected intrasplenically to create CRLM model. Single-cell RNA sequencing (scRNA-seq), RT-PCR and immunohistology were used to study hepatic immune-cell composition, phenotypes, and localization.</div></div><div><h3>Results</h3><div>Both diets significantly increased CRLM establishment, while only WD altered hepatic inflammation. The WD-promotes IL-10 and TGF-β1 elevation, an anti-inflammatory cytokines, inhibiting cytotoxic CD8⁺ T cells and NK cells and supporting an immunosuppressive environment. Although MASH led to an increased presence of hepatic CD8⁺ and NK cells, their infiltration into metastatic foci was reduced and was associated with a decrease in expression of cytotoxic markers. In our murine model of MASH, CD8⁺ T-cell depletion reduced the number of CRLM foci, which was accompanied by a decrease in IFN-γ-associated cytokines and a significant increase in the infiltration of granzyme-B expressing NK cells, ultimately enhancing cytotoxic killing ability.</div></div><div><h3>Conclusions</h3><div>This research underscores the crucial influence of diet-induced immune changes on CRLM establishment and progression. It illustrates that the co-localization of immune cells within liver metastases significantly affects their functionality, highlighting potential therapeutic strategies to balance immune exhaustion and activation.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"69 ","pages":"Article 101222"},"PeriodicalIF":7.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144907856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PD-L1(+) tumor-associated macrophages induce CD8(+) T Cell exhaustion in hepatocellular carcinoma","authors":"Takuto Nosaka ,&nbsp;Masahiro Ohtani ,&nbsp;Junki Yamashita ,&nbsp;Yosuke Murata ,&nbsp;Yu Akazawa ,&nbsp;Tomoko Tanaka ,&nbsp;Kazuto Takahashi ,&nbsp;Tatsushi Naito ,&nbsp;Yoshiaki Imamura ,&nbsp;Kenji Koneri ,&nbsp;Takanori Goi ,&nbsp;Yasunari Nakamoto","doi":"10.1016/j.neo.2025.101234","DOIUrl":"10.1016/j.neo.2025.101234","url":null,"abstract":"<div><div>The therapeutic efficacy of immune checkpoint inhibitors (ICIs) in patients with hepatocellular carcinoma (HCC) is profoundly influenced by the tumor immune microenvironment (TIME), where tumor-associated macrophages (TAMs) expressing programmed death-ligand 1 (PD-L1) serve as key modulators of immune suppression and tumor progression. Although PD-L1(+) TAMs have attracted increasing attention, their precise immunological functions in patients with HCC remain incompletely understood. In this study, we conducted an integrated analysis combining single-cell transcriptomics, spatial profiling, <em>in vitro</em> functional assays, and <em>in vivo</em> therapeutic modeling to clarify the role of PD-L1(+) TAMs in HCC. Single-cell RNA sequencing of tumor samples from patients with HCC (GSE189903) revealed that intratumoral PD-L1(+) TAMs were enriched for immune-related signaling pathways and expressed chemokines including CXCL9, CXCL10, and CXCL11. In vitro, GM-CSF–induced PD-L1(+) macrophages promoted CD8(+) T cell exhaustion, characterized by increased expression of TIM3 and suppression of cytotoxic molecules such as GZMB. Spatial analysis using multiplex immunofluorescence staining of surgical specimens from 113 patients with HCC demonstrated that close proximity between PD-L1(+) TAMs and CD8(+) T cells within tumors was an independent predictor of early postoperative recurrence and poor outcome. Moreover, in a murine orthotopic liver cancer model, the combination of anti–GM-CSF and anti–PD-L1 antibodies inhibited the differentiation of PD-L1(+) TAMs, reduced their contact with CD8(+) T cells, alleviated T cell exhaustion, and potentiated antitumor immunity. These findings highlight the critical contribution of PD-L1(+) TAMs to immune evasion in patients with HCC and support their therapeutic targeting as a strategy to enhance ICI responses.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"69 ","pages":"Article 101234"},"PeriodicalIF":7.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145201187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PDGFRA in paediatric high-grade glioma – target or distraction?","authors":"Natalie Le ,&nbsp;Jingwei Chen ,&nbsp;Paul G. Ekert ,&nbsp;Lauren M. Brown ,&nbsp;Neevika Manoharan","doi":"10.1016/j.neo.2025.101231","DOIUrl":"10.1016/j.neo.2025.101231","url":null,"abstract":"<div><div>Paediatric high-grade gliomas (pHGGs) are aggressive and molecularly heterogenous paediatric brain tumours with extremely poor survival outcomes. Receptor tyrosine kinases (RTKs) are recurrently altered in a significant proportion of pHGGs and can be potentially targeted with tyrosine kinase inhibitors (TKIs). <em>PDGFRA</em> is the most frequently altered RTK in pHGG and as such, represents an attractive therapeutic target, yet patients harbouring <em>PDGFRA</em> aberrations have largely failed to respond to TKIs. This raises the question as to whether PDGFRA is the only oncogenic dependency in all cases of pHGG, or alternatively, if there are unrecognised mechanisms conferring TKI resistance. Here we explore the mechanisms by which specific PDGFRA alterations drive oncogenesis and potentially mediate therapeutic resistance, to ascertain whether PDGFRA is a clinically useful target or merely a distraction.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"69 ","pages":"Article 101231"},"PeriodicalIF":7.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic analysis uncovers biological diversity in molecularly defined endometrial carcinomas","authors":"Dawn R. Cochrane ,&nbsp;Gian Luca Negri ,&nbsp;Jutta Huvila ,&nbsp;Forouh Kalantari ,&nbsp;David A. Farnell ,&nbsp;Nissreen Mohammad ,&nbsp;Emily Thompson ,&nbsp;Winnie Yang ,&nbsp;Amy Lum ,&nbsp;Sandra E. Spencer ,&nbsp;Ryan Riley ,&nbsp;Amy Jamieson ,&nbsp;Samuel Leung ,&nbsp;Derek Chiu ,&nbsp;Christine Chow ,&nbsp;Jamie L.P. Lim ,&nbsp;Martin Köbel ,&nbsp;Stefan Kommoss ,&nbsp;Friedrich Kommoss ,&nbsp;Blake Gilks ,&nbsp;Jessica N. McAlpine","doi":"10.1016/j.neo.2025.101229","DOIUrl":"10.1016/j.neo.2025.101229","url":null,"abstract":"<div><div>While endometrial cancer has an overall favorable prognosis, some patients have poor outcomes and may benefit from further refinements of the current classification systems. Molecular classification stratifies endometrial cancer patients into four prognostic subtypes: <em>POLE</em>mut, MMRd (mismatch repair deficient), p53abn, and NSMP (no specific molecular profile), where patients with <em>POLE</em>mut have the best prognosis and p53abn has the worst prognosis. We used proteomic profiling to assess if additional prognostic or predictive information could be identified across or within molecular subtypes. Global proteome profiling of formalin fixed, paraffin embedded samples, that had clinicopathologic and outcome data, was performed on 184 endometrial cancers encompassing all four molecular subtypes, including replicate samples of the same tumor, and both biopsy and final hysterectomy specimens. To ensure representation of each subtype, we profiled an approximately equal distribution in the 148 unique tumors; 34 (23%) <em>POLE</em>mut, 40 (27%) MMRd, 35 (24%) p53abn and 39 (26%) NSMP, rather than the population-based distributions. There was high reproducibility in the proteomic profiles of intra-tumor replicate samples, and between matched biopsy and hysterectomy tumor samples. Consensus clustering identified four clusters with different prognosis, named ‘Adhesion’, ‘Immune’, ‘Proliferation’, and ‘Metabolic’ based on the functional characteristics of the enriched proteins. We associated protein expression features with common mutations, molecular subtype, and outcomes. These results demonstrate the biologic diversity within endometrial cancers, both between and within molecular subtypes, and provide candidate features for functional and clinical investigation.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"69 ","pages":"Article 101229"},"PeriodicalIF":7.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145087803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Single-cell proteomic analysis reveals Multiple Myeloma heterogeneity and the dynamics of the tumor immune microenvironment in precursor and advanced states” [Neoplasia 66 (2025) 1101189]","authors":"Mohamed Kamal ,&nbsp;Stephanie N. Shishido ,&nbsp;Jeremy Mason ,&nbsp;Krina Patel ,&nbsp;Elisabet E. Manasanch ,&nbsp;Robert Z. Orlowski ,&nbsp;Peter Kuhn","doi":"10.1016/j.neo.2025.101226","DOIUrl":"10.1016/j.neo.2025.101226","url":null,"abstract":"","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"69 ","pages":"Article 101226"},"PeriodicalIF":7.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145004604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}