Pathobiology最新文献

{"title":"The Human Immunodeficiency Virus Type 1 Budding Machinery: Deconstructing the Endosomal Sorting Complexes Required for Transport-Mediated Scission Pathway.","authors":"Mahmoud M Yaseen, Nizar Abuharfeil","doi":"10.1159/000551438","DOIUrl":"10.1159/000551438","url":null,"abstract":"<p><strong>Background: </strong>The final step of the Human immunodeficiency virus type 1 (HIV-1) replication cycle, virion budding and scission from the host cell membrane, is executed not by a viral enzyme but by the hijacked host endosomal sorting complexes required for transport (ESCRT) machinery.</p><p><strong>Summary: </strong>This review synthesizes current knowledge on how HIV-1 Gag polyprotein recruits and coordinates the ESCRT pathway. We detail the critical roles of the PTAP and YPX_nL late-domain motifs in engaging Tsg101 (ESCRT-I) and ALIX adaptors, which nucleate the assembly of constrictive ESCRT-III polymers and the VPS4 ATPase to catalyze membrane fission. We examine the plasticity of these recruitment pathways, the regulatory influence of ubiquitination, and how cell-type-specific factors impact budding efficiency. Furthermore, we assess emerging connections between ESCRT function, viral pathogenesis, and therapeutic opportunities.</p><p><strong>Key messages: </strong>The ESCRT-dependent budding of HIV-1 is a robust yet vulnerable process, characterized by redundant entry points converging on an essential core scission engine. This mechanistic understanding reveals critical virus-host interfaces that present promising targets for novel antiviral strategies aimed at disrupting this late stage of the viral life cycle.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-23"},"PeriodicalIF":2.0,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147675366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FAT1 Is Differentially Expressed in Cancers Affecting the Serosal Cavities.","authors":"Ben Davidson, Arild Holth","doi":"10.1159/000551734","DOIUrl":"10.1159/000551734","url":null,"abstract":"<p><strong>Introduction: </strong>FAT1 is mutated in many types of cancer. The objective of this study was to analyze the diagnostic role of FAT1 protein in cancers affecting the serosal cavities.</p><p><strong>Methods: </strong>FAT1 protein expression by immunohistochemistry was analyzed in 256 effusions (139 peritoneal, 116 pleural, 1 pericardial), consisting of 96 tubo-ovarian carcinomas, 56 breast carcinomas, 44 mesotheliomas, 28 uterine corpus and cervical carcinomas, 15 lung carcinomas, 13 gastrointestinal carcinomas, and 4 cancers of other origin.</p><p><strong>Results: </strong>FAT1 expression was most common in gastrointestinal carcinomas (12/13; 92%), followed by lung (9/15; 60%), breast (31/56; 55%), and uterine cervical (4/8; 50%) carcinomas, with infrequent expression in other tumors, including tubo-ovarian carcinomas (5/96; 5%). Mesotheliomas were uniformly negative. Staining of a limited series of surgical specimens showed comparable results for patient-matched breast carcinomas (29/41; 71%), whereas tubo-ovarian carcinomas were more frequently positive (16/57; 28%), though often focally, compared to effusions. Eight epithelioid mesotheliomas were negative (0/8; 0%). Survival analysis for 42 breast carcinoma patients with effusion for whom clinical data were available showed no association with overall (p = 0.398) or disease-free (p = 0.255) survival.</p><p><strong>Conclusion: </strong>FAT1 is commonly expressed in carcinomas of gastrointestinal, lung, or breast origin but is rarely expressed in tubo-ovarian carcinoma effusions and is absent in mesothelioma. Whether this difference is of use in the diagnostic setting remains to be established.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-8"},"PeriodicalIF":2.0,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147531721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chimeric Antigen Receptor Natural Killer T-Cell Therapy for Tumors: Promise and Progress.","authors":"Ruo-Bing Wang, Xuan Wang, Kun-Kun Han, Guo-Dong Chen, Yi-Li Yang, Xin Xu, Tao Zhang","doi":"10.1159/000551197","DOIUrl":"10.1159/000551197","url":null,"abstract":"<p><strong>Background: </strong>Therapy based on chimeric antigen receptor-engineered invariant natural killer T cells (chimeric antigen receptor natural killer T [CAR-NKT] cells) is an innovative cellular immunotherapy strategy that offers advantages over conventional CAR-T cell therapy in the treatment of solid tumors.</p><p><strong>Summary: </strong>This article reviewed the research progress and current application of CAR-NKT cells in solid tumors. Current studies have shown that CAR-NKT cells can efficiently recognize tumor-associated antigens, infiltrate the tumor microenvironment, and exert antitumor effects through direct killing and cytokine secretion. Compared with CAR-T therapy, CAR-NKT therapy exhibits stronger antitumor potency and a reduced incidence of graft-versus-host disease. Furthermore, CAR-NKT cells can enhance antitumor immunity by regulating dendritic cells, NK cells, and CD8+ T cells. Early clinical trials for neuroblastoma and preclinical trials for other solid tumors have shown good safety and preliminary efficacy, and therapies have great potential for clinical translation.</p><p><strong>Key messages: </strong>However, this therapy still faces challenges such as optimizing antigen selection, insufficient in vivo expansion and persistence, tumor heterogeneity, and immune suppression barriers. Future directions include advancing cytokine engineering and combination therapies. Collectively, CAR-NKT cells provide new ideas and new means to break through the difficulties in treating solid tumors and hold the promise of becoming the next generation of cellular immunotherapy.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-13"},"PeriodicalIF":2.0,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147321853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in Renal Cell Carcinoma Diagnosis: A Review on Biomarkers.","authors":"Agnese Orsatti, Fernanda Fernandes-Pontes, João Ricardo E Silva, Nuno Tiago Tavares, Carmen Jerónimo, Rui Henrique, Ângelo Rodrigues, Costantino Ricci, João Lobo","doi":"10.1159/000550723","DOIUrl":"10.1159/000550723","url":null,"abstract":"<p><strong>Background: </strong>Renal cell carcinoma (RCC) is a heterogeneous disease, with the last World Health Organization (WHO) classification introducing several novel entities, among which the molecularly defined RCCs. This growing complexity highlights the need for integration of morphology, immunohistochemistry (IHC) and molecular techniques, ensuring accurate classification and reducing the \"RCC not otherwise specified (NOS) category.\"</p><p><strong>Summary: </strong>Molecular assays such as next-generation sequencing (NGS) and fluorescence in situ hybridization (FISH) are increasingly necessary for diagnosing molecularly defined RCCs. IHC remains fundamental for diagnosing both \"old\" and newly defined RCCs, representing a surrogate for molecular alterations such as fumarate-hydratase and succinate-dehydrogenase deficiency, anaplastic lymphoma kinase rearrangements, SMARCB1 loss, and TFE3 rearrangements. However, entities like ELOC-mutated RCC require molecular testing for diagnosis. Liquid biopsy offers a further diagnostic tool. Circulating microRNAs can support diagnosis, classification, and monitoring. Furthermore, circulating tumor DNA (ctDNA) methylation analyses and circulating tumor cells (CTCs) offer promising and minimally invasive tools for stratification, though their clinical use is still evolving.</p><p><strong>Key messages: </strong>A precise diagnosis integrating histopathology, IHC, and molecular testing is critical for guiding management, identifying hereditary syndromes, and implementing personalized tumor biology-based therapies. With evolving molecular diagnostic and circulating biomarkers, careful clinical integration is needed to optimize outcomes and treatment.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-20"},"PeriodicalIF":2.0,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146065897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictive Histopathological Markers for Upstaging to Invasive Carcinoma after a Biopsy Diagnosis of Ductal Carcinoma in situ of the Breast: A Hypothesis-Generating Systematic Review.","authors":"Julia A M Riggi, Ibrahim Kassem, Christine Galant, Carolien H M van Deurzen, Martine Berlière, Mieke R Van Bockstal","doi":"10.1159/000547335","DOIUrl":"10.1159/000547335","url":null,"abstract":"<p><strong>Introduction: </strong>Around 25% of patients with a biopsy diagnosis of pure ductal carcinoma in situ (DCIS) will be upstaged to invasive breast carcinoma (IBC) after surgery. Because of this upstaging risk, patients with high grade DCIS frequently undergo a sentinel lymph node procedure (SLNP), which can cause surgery-induced morbidity. Presentation with a palpable mass increases the upstaging risk, but histopathological predictors are currently unclear. This PROSPERO-registered systematic review aims to identify which biopsy-based histopathological markers can predict the presence of IBC in the subsequent resection. These results might help to reserve SLNPs for selected high-risk patients, aiming to personalize treatment.</p><p><strong>Methods: </strong>PubMed, Embase, and Scopus were searched for content using predefined search queries. Three reviewers independently screened the literature in Rayyan by applying predefined criteria and retained 36 reports. Studies including DCIS with micro-invasion were excluded.</p><p><strong>Results: </strong>This systematic review comprised 18,475 patients. The median cohort size was 267 patients (range: 67-3,780). Most studies were retrospective (33/36). The median upstaging risk was 26% (range: 8-52%). The reports studied twenty-three histopathological and immunohistochemical features. Only seven features were investigated in multiple studies, all yielding contradictory results. For instance, thirty-three studies investigated nuclear grade, but only 18 reports demonstrated a significant association with upstaging, independent from cohort size.</p><p><strong>Conclusion: </strong>No robust histopathological features can be recommended at present to reliably predict the upstaging risk to IBC after a biopsy diagnosis of pure DCIS. We discuss several hypotheses, aiming to explain these contradictory data. Ideally, large-scale multicentre prospective studies should be organized to answer this unmet clinical need.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"34-47"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HPV ctDNA as a Biomarker for Monitoring Disease Progression in HPV16/18-Associated Cervical Cancer.","authors":"Meejeong Kim, Miseon Lee, Jun Kang, Sung Jong Lee, Sook Hee Hong, Keun Ho Lee, Ahwon Lee","doi":"10.1159/000548452","DOIUrl":"10.1159/000548452","url":null,"abstract":"<p><strong>Introduction: </strong>Cervical cancer, primarily driven by oncogenic HPV16/18, often relapses despite standard treatments. HPV circulating tumor DNA (ctDNA), which reflects tumor-derived genetic material in the bloodstream, has emerged as a promising noninvasive biomarker for monitoring disease progression.</p><p><strong>Methods: </strong>A prospective study was conducted on 20 patients with HPV16/18-associated cervical cancer. Posttreatment blood samples were collected, and HPV ctDNA levels were measured using droplet digital PCR. The correlation between HPV ctDNA levels and disease progression was examined.</p><p><strong>Results: </strong>HPV ctDNA was detected in 21% (18/85) of samples, with 6% (5/85) showing positivity. Patients without disease progression (n = 15) were HPV ctDNA negative, indicating a false positivity rate of zero. HPV ctDNA concentrations appeared higher in samples collected before or during disease progression, suggesting a potential association with disease status. Patients with positive HPV ctDNA tended to have shorter progression-free survival compared to those with negative ctDNA.</p><p><strong>Conclusions: </strong>This study suggests that HPV ctDNA may aid in monitoring disease progression in patients with HPV16/18-associated cervical cancer, highlighting the need for further validation.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"87-95"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of the Molecular Subtype-Dependent Immune Microenvironment of Metastatic Axillary Lymph Nodes on Breast Cancer Patient Outcomes.","authors":"Carlos López, Laia Reverté, Ramon Bosch Príncep, Esther Sauras, Noèlia Gallardo-Borràs, Alba Fischer-Carles, Anna Korzynska, Marcial García-Rojo, Gloria Bueno, Lukasz Roszkowiak, Albert Roso-LLorach, Andrea Gras Navarro, Montserrat Llobera, Daniel Mata, Laia Adalid Llansa, Salomé Martínez-González, Joan F Garcia-Fontgivell, Meritxell Arenas, Junior Gómez, José Antonio Izuel, Jordi Baucells, Marylène Lejeune","doi":"10.1159/000550086","DOIUrl":"10.1159/000550086","url":null,"abstract":"<p><p><p>Introduction: Metastasis in the axillary lymph nodes (ALNs) occurs in 30-50% of breast cancers (BCs), where residing immune cells play a crucial role in disease progression. Specifically at diagnosis, the immune elements infiltrating the primary tumour are among the best established prognostic factors. However, their prognostic value in the metastatic ALNs (ALNs+) is poorly understood.</p><p><strong>Methods: </strong>We aimed to retrospectively assess the immune populations of ALNs+ in luminal A (LA) and triple-negative BC (TNBC) patients using immunohistochemistry, to compare it with non-metastatic ALNs (ALNs-), and to determine their relationship with patient outcomes.</p><p><strong>Results: </strong>We found differences in the immune concentrations of matched ALNs (ALNs- vs. ALNs+) from patients with positive nodal status in either LA or TNBC subtypes. In contrast, compared with LA, the levels of immune cells in ALNs- of the TNBC profile differ much more from ALNs+ than in the LA subtype, regardless of the nodal status. In addition, TNBC patients with higher levels of CD4 and CD8 lymphocytes in ALNs+ have worse cancer-specific survival (CSS) and higher levels of CD83 dendritic cells (DCs) are related to worse CSS and time to progression (TTP). Conversely, LA patients with higher levels of CD21 DC showed better TTP.</p><p><strong>Conclusion: </strong>Our results showed that ALN immune profiles and their influence on disease evolution vary by molecular BC subtype and nodal status, suggesting that accurate ALN immune profiling at diagnosis could provide new insights into the immune BC landscape. These observations require validation in larger, prospective cohorts before they can be reliably used to inform clinical decision-making. </p>.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"147-159"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12863725/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145878760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Establishment of a Novel Organoid Line from Esophageal Squamous Cell Carcinoma with Cytoplasmic Vacuoles: Association of Autolysosome Swelling with Vacuole Formation.","authors":"Shunsuke Fujita, Tomotaka Shibata, Haruto Nishida, Sawa Matsumoto, Shusaku Kurogi, Shinji Yano, Shoichi Fumoto, Yusuke Itai, Yuki Shitomi, Tomonori Akagi, Shigeo Ninomiya, Tsuyoshi Etoh, Chisato Nakada, Takafumi Fuchino, Yuka Hirashita, Kazuhiro Mizukami, Tsutomu Daa, Masafumi Inomata, Masatsugu Moriyama, Naoki Hijiya, Yoshiyuki Tsukamoto","doi":"10.1159/000548788","DOIUrl":"10.1159/000548788","url":null,"abstract":"<p><strong>Introduction: </strong>We experienced a case of esophageal squamous cell carcinoma (ESCC) exhibiting mucus-negative cytoplasmic vacuoles. The carcinoma cells with vacuoles were positive for p63, a marker of squamous cell carcinoma (SCC). Since the first description by Cramer and Heggeness in 1989, 24 cases of SCC with mucus-negative vacuoles have been reported to date. However, little is known about the clinical course of SCC with vacuoles (SCCVs) and the nature of the cytoplasmic vacuoles themselves, due to its rarity and the lack of suitable models.</p><p><strong>Methods: </strong>We established a novel organoid line - designated ECO_Vac - from residual cancer tissue of a patient with esophageal SCCV (ESCCV) after neoadjuvant chemotherapy, evaluated its applicability as a model of ESCCV, and characterized its cytoplasmic vacuoles by electron microscopic and organelle-specific fluorescent probe uptake assays.</p><p><strong>Results: </strong>ECO_Vac was successfully established and was found to be applicable to in vitro drug assays and experiments involving in vivo tumor formation. We also found that the vacuoles in ESCCV were enlarged autolysosomes.</p><p><strong>Conclusion: </strong>We established a novel organoid line, ECO_Vac, as a useful model for investigating the molecular pathogenesis of ESCCV. By using ECO_Vac, we demonstrated that the cytoplasmic vacuoles in ESCCV were unphysiologically enlarged autolysosomes.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"123-134"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145471596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"REV7 Expression Is Associated with Tumor Cell Growth and Cisplatin Resistance in Gallbladder Adenocarcinoma.","authors":"Masahiro Matsushita, Takuya Kato, Yasutaka Sakurai, Masaaki Ichinoe, Taro Kogami, Akihiro Tamaki, Yurika Kesen, Shoko Hayashi, Itaru Sanoyama, Yoshiko Numata, Atsuko Umezawa, Masatoshi Ichihara, Chika Kusano, Yoshiki Murakumo","doi":"10.1159/000549588","DOIUrl":"10.1159/000549588","url":null,"abstract":"<p><strong>Introduction: </strong>REV7 functions in various biological processes, including the DNA damage response. REV7 expression has been linked to the prognosis and chemoresistance in several human cancers. This study investigated the significance of REV7 in gallbladder adenocarcinoma (GBAC).</p><p><strong>Methods: </strong>REV7 expression was examined immunohistochemically in 77 resected GBAC specimens, and its association with clinicopathological features was analyzed. REV7-depleted GBAC cell lines were established, and the biological effects of REV7 depletion were evaluated.</p><p><strong>Results: </strong>High REV7 expression in GBAC tissues correlated with increased cell proliferation, as assessed by Ki-67 labeling indices (p < 0.001), and was associated with a trend toward shorter overall survival (p = 0.070) and significantly shorter post-progression survival (p = 0.035). REV7-knockout and REV7-knockdown cell lines derived from NOZ and G415 GBAC cells (NOZ-KO and G415-KD, respectively) showed reduced proliferation and increased sensitivity to cisplatin; however, REV7 depletion did not affect cell migration and invasion. Reintroduction of REV7 into NOZ-KO cells restores chemoresistance. Furthermore, RNA sequencing analysis comparing wild-type NOZ and NOZ-KOs revealed that REV7 inactivation downregulates genes involved in the DNA damage response.</p><p><strong>Conclusion: </strong>REV7 may contribute to tumor progression and chemoresistance in GBAC and may serve as a prognostic biomarker and molecular target for GBAC management.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"187-199"},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145945494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"2,3-Pyridinedicarboxylate Is Associated with Shorter Recurrence-Free Survival in Patients with Hypopharyngeal Squamous Cell Carcinoma.","authors":"Hiroki Takase, Takao Fujisawa, Ryuichi Hayashi, Hideki Makinoshima, Yutaka Suzuki, Tomoyoshi Soga, Satoshi Fujii","doi":"10.1159/000548128","DOIUrl":"10.1159/000548128","url":null,"abstract":"<p><p><p>Introduction: Metabolites are associated with the biology of cancer; however, no metabolites related to prognosis have been identified in head and neck cancer. This study aimed to identify metabolites associated with prognosis in patients with hypopharyngeal squamous cell carcinoma (HPSCC).</p><p><strong>Methods: </strong>Fifty-two patients who underwent surgery for HPSCC were included and randomly divided into test and validation cohorts of 26 patients each for further metabolome analysis using capillary electrophoresis/mass spectrometry on tumor and non-tumor tissues of the hypopharynx. Twenty-two patients who received adjuvant therapy after surgery were included. The receiver operating characteristic (ROC) and univariate and multivariate analyses were used to explore the relationship between recurrence-free survival (RFS), clinicopathological factors, and differentiated metabolites.</p><p><strong>Results: </strong>ROC analysis revealed six metabolites significantly associated with RFS in both cohorts, and multivariate analysis indicated that 2,3-pyridinedicarboxylate was a significantly independent poorer prognostic factor in the cohorts including patients with HPSCC without any adjuvant therapies (p = 0.017).</p><p><strong>Conclusion: </strong>2,3-Pyridinedicarboxylate, involved in NAD+ metabolism and genomic stability, suggests the possibility of developing molecular-targeted drugs for the production of metabolites related to prognosis. This study identifies novel prognostic metabolites and their associated metabolic pathways in HPSCC, highlighting potential therapeutic targets for treatment. </p>.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"72-86"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12503820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144964286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}