{"title":"Identification of a metabolic-immune signature associated with prognosis in colon cancer and exploration of potential predictive efficacy of immunotherapy response.","authors":"Yuwen Xie, Shenyuan Guan, Zhenkang Li, Guohao Cai, Yuechen Liu, Guoxin Li, Ping Huang, Mingdao Lin","doi":"10.1007/s10238-025-01566-6","DOIUrl":"10.1007/s10238-025-01566-6","url":null,"abstract":"<p><p>The role of metabolic reprogramming of the tumor immune microenvironment in cancer development and immune escape has increasingly attracted attention. However, the predictive value of differences in metabolism-immune microenvironment on the prognosis of colon cancer (CC) and the response to immunotherapy have not been elucidated. The aim of this study was to investigate changes in metabolism and immune profile of CC and to identify a reliable signature for predicting prognosis and therapeutic response. The metabolism and immune-related differential genes in CC were screened out by differential gene expression analysis. A metabolism and immune related prognostic signature was established by the least absolute shrinkage and selection operator (LASSO) Cox algorithm. The training cohort with 417 patients from The Cancer Genome Atlas (TCGA) database and the validation cohort of 232 patients from GSE17538 were used to confirm the robustness of the prognostic signature. Immunohistochemical staining scores were used to assess gene expression levels in our clinical samples. Gene ontology (GO) analysis, gene set enrichment analysis (GSEA), single nucleotide variation (SNV) analysis, immune infiltration and immune factors analysis were used to explore the characteristics of patients with different subtypes. Multiple cancer immunotherapy datasets were used to assess the response of patients with different subtypes to immune checkpoint inhibitors. We established the Metabolism and Immune-Related Prognostic Score (MIRPS) based on six genes (CD36, PCOLCE2, SCG2, CALB2, STC2, CLDN23) to predict the prognosis of CC patients. We found a correlation between MIRPS and the malignant phenotype, microsatellite subtype, mutation load, and immune escape in CC. Tumors with high MIRPS presented a higher tumor mutation load and a more prominent immunosuppressive microenvironment. This subset of patients may potentially respond well to immune checkpoint inhibitor therapy. MIRPS may be used as a novel prognostic tool for CC and have potential value for immunotherapy response prediction.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"46"},"PeriodicalIF":3.2,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143032133","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":"Cellular senescence in the tumor with a bone niche microenvironment: friend or foe?","authors":"Sajad Alavimanesh, Negar Nayerain Jazi, Maedeh Choubani, Farzane Saeidi, Hamed Afkhami, Aref Yarahmadi, Hossein Ronaghi, Pouria Khani, Mohammad Hossein Modarressi","doi":"10.1007/s10238-025-01564-8","DOIUrl":"10.1007/s10238-025-01564-8","url":null,"abstract":"<p><p>Cellular senescence is understood to be a biological process that is defined as irreversible growth arrest and was originally recognized as a tumor-suppressive mechanism that prevents further propagation of damaged cells. More recently, cellular senescence has been shown to have a dual role in prevention and tumor promotion. Senescent cells carry a senescence-associated secretory phenotype (SASP), which is altered by secretory factors including pro-inflammatory cytokines, chemokines, and other proteases, leading to the alteration of the tissue microenvironment. Though senescence would eventually halt the growth of cancerous potential cells, SASP contributes to the tumor environment by promoting inflammation, matrix remodeling, and tumor cell invasion. The paradox of tumor prevention/promotion is particularly relevant to the bone niche tumor microenvironment, where longer-lasting, chronic inflammation promotes tumor formation. Insights into a mechanistic understanding of cellular senescence and SASP provide the basis for targeted therapies, such as senolytics, which aim to eliminate senescent cells, or SASP inhibitors, which would eliminate the tumor-promoting effects of senescence. These therapeutic interventions offer significant clinical implications for treating cancer and healthy aging.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"44"},"PeriodicalIF":3.2,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11759293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028080","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}
Renata Pacholczak-Madej, Artur Drobniak, Aleksandra Grela-Wojewoda, Jacek Calik, Natalia Versuti Viegas, Daria Tusień-Małecka, Jolanta Dobrzańska, Agnieszka Roman, Anna Bidas, Marek Szwiec, Angelika Gawlik-Urban, Jerzy Walocha, Paweł Blecharz, Łukasz Stokłosa, Mirosława Puskulluoglu
{"title":"Prognostic significance of peripheral blood biomarkers in patients with advanced renal cell carcinoma treated with nivolumab and ipilimumab-a polish multicenter, observational study.","authors":"Renata Pacholczak-Madej, Artur Drobniak, Aleksandra Grela-Wojewoda, Jacek Calik, Natalia Versuti Viegas, Daria Tusień-Małecka, Jolanta Dobrzańska, Agnieszka Roman, Anna Bidas, Marek Szwiec, Angelika Gawlik-Urban, Jerzy Walocha, Paweł Blecharz, Łukasz Stokłosa, Mirosława Puskulluoglu","doi":"10.1007/s10238-024-01544-4","DOIUrl":"10.1007/s10238-024-01544-4","url":null,"abstract":"<p><p>Immune checkpoint inhibitors have improved the treatment of metastatic renal cell carcinoma (RCC), with the combination of nivolumab (NIVO) and ipilimumab (IPI) showing promising results. However, not all patients benefit from these therapies, emphasizing the need for reliable, easily assessable biomarkers. This multicenter study involved 116 advanced RCC patients treated with NIVO + IPI across nine oncology centers in Poland. Blood markers such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR), eosinophils, and monocytes were assessed at baseline, after three months, and before disease progression (PD). The prognostic significance of these parameters was analyzed using linear regression, Kaplan-Meier survival analysis, and Cox regression models. After a median follow-up of 11.8 months, the progression-free survival (PFS) was 12.8 months (95% confidence interval [CI] 5.7-28.1), while the overall survival (OS) was 27.3 months (95% CI 16-not reached). Patients with an NLR increase of ≥ 25% had a PFS of 8.2 (3.1-24.7) months compared to 17.5 (8.6-28.1) months in those with a rise in < 25% (p = 0.015). Similarly, a ≥ 25% increase in PLR was linked to a PFS of 6.8 (2.8-8.3) months compared to 17.4 (8.4-28.1) months (p < 0.001). Multivariate analysis confirmed PLR as an independent predictor of PFS (HR 2.9, 95% CI 1.5-5.6, p = 0.001), while elevated eosinophil levels were associated with a reduced risk of death (HR 0.2, 95% CI 0.04-0.9, p = 0.05). No other analysis was statistically significant. NLR, PLR, and eosinophil levels may serve as valuable biomarkers for predicting treatment response in RCC patients receiving NIVO + IPI.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"45"},"PeriodicalIF":3.2,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11759459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028081","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":"Role of immune cell homeostasis in research and treatment response in hepatocellular carcinoma.","authors":"Weihua Song, Meng Li, Wangrui Liu, Wenhao Xu, Hongyun Zhou, Shiyin Wei, Jiachang Chi","doi":"10.1007/s10238-024-01543-5","DOIUrl":"https://doi.org/10.1007/s10238-024-01543-5","url":null,"abstract":"<p><p>Introduction Recently, immune cells within the tumor microenvironment (TME) have become crucial in regulating cancer progression and treatment responses. The dynamic interactions between tumors and immune cells are emerging as a promising strategy to activate the host's immune system against various cancers. The development and progression of hepatocellular carcinoma (HCC) involve complex biological processes, with the role of the TME and tumor phenotypes still not fully understood. Therefore, it is essential to investigate the importance of immune cell homeostasis in HCC. Additionally, understanding the molecular mechanisms and biological functions underlying tumor-immune cell interactions is increasingly recognized as vital for improving therapeutic outcomes in clinical settings. Methods A total of 790 HCC samples were selected from public databases and real-world independent clinical cohorts. Machine learning methods, focusing on immune-related indicators, were applied to these samples. The Boruta algorithm was employed to develop an ICI score, which was used to assess patient prognosis and predict responses to immunotherapy. Additionally, a new immune subtype analysis of HCC was performed. Cellular-level experiments confirmed the interaction between TME-related factors and the tumor microenvironment in HCC. To further validate the predictive power of the ICI score, a clinical cohort study was conducted at an independent clinical center. Results By evaluating immune gene expression levels, immune cell abundance, Immunescore, and Stromalscore, we initially identified three distinct immune subtypes of HCC, each showing significant differences in survival rates and heterogeneity. Subsequently, DEGs from 1022 immune subtypes were used to classify HCC samples into three immune genotypes, each characterized by distinct prognosis and tumor immune microenvironment (TIME) profiles. Furthermore, we developed the ICI score, a novel immunophenotyping method for HCC, which revealed significant variations based on gender, stage, progression, and DNA mutation profiles (p < 0.05). The ICI score also effectively predicted responses to immunotherapies, particularly through the chemokine signaling, focal adhesion, and JAK/STAT signaling pathways. Conclusion This research demonstrated that TME and immunophenotyping clusters can enhance prognostic accuracy for HCC patients. The independent prognostic indicators identified underscore the connection between tumor phenotype and the immune environment in HCC.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"42"},"PeriodicalIF":3.2,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001093","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}
Mona Rady, Maha Mostafa, Gabriel Dida, Fatima Sabet, Khaled Abou-Aisha, Carsten Watzl
{"title":"Adoptive NK cell therapy in AML: progress and challenges.","authors":"Mona Rady, Maha Mostafa, Gabriel Dida, Fatima Sabet, Khaled Abou-Aisha, Carsten Watzl","doi":"10.1007/s10238-025-01559-5","DOIUrl":"10.1007/s10238-025-01559-5","url":null,"abstract":"<p><p>Adoptive cell therapy (ACT) using natural killer (NK) cells has emerged as a promising therapeutic strategy for acute myeloid leukemia (AML), addressing challenges such as chemotherapy resistance and high relapse rates. Over the years, clinical trials and studies have explored various sources of NK cells, including ex vivo expanded NK cell lines, CAR-NK cells, peripheral blood-derived NK cells, and umbilical cord blood-derived NK cells. These therapies have demonstrated varying degrees of therapeutic efficacy, ranging from transient anti-leukemia activity to sustained remission in select patient groups. Toxicity profiles have generally shown favorable safety outcomes, with minimal incidence of severe adverse effects such as cytokine release syndrome (CRS) or graft-versus-host disease (GVHD). However, persistent challenges remain, including limited NK cell persistence, relapse, and heterogeneity in patient responses. This review provides a comprehensive analysis of clinical outcomes and toxicity profiles provided from clinical trials, clinical studies and case reports conducted in the last 15 years to judge on the efficacy, safety and applicability of using NK cells for ACT of AML. Our review highlights the significant potential of NK cell-based therapies for AML, while addressing the technical and biological challenges that must be overcome to enhance their efficacy and safety.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"41"},"PeriodicalIF":3.2,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001147","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":"The association between immunoinflammatory biomarkers NLR, PLR, LMR and nonalcoholic fatty liver disease: a systematic review and meta-analysis.","authors":"Yunyi Yang, Xiaoli He, Shufa Tan, Xiaoxiao Qu, Weijin Huang, Jiayuan Cai, Jiawen You, Xinyi Fu, Yanming He, Hongjie Yang","doi":"10.1007/s10238-024-01539-1","DOIUrl":"10.1007/s10238-024-01539-1","url":null,"abstract":"<p><p>Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disorder closely linked to metabolic syndrome. Identifying novel, easily measurable biomarkers could significantly enhance the diagnosis and management of NAFLD in clinical settings. Recent studies suggest that immunoinflammatory biomarkers-specifically, the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR)-may offer diagnostic value for NAFLD. However, the effectiveness of these biomarkers has not been comprehensively assessed in this patient population. This systematic review and meta-analysis aimed to evaluate the association between these immunoinflammatory biomarkers and NAFLD. As of August 8, 2024, databases including PubMed, EMBASE, Cochrane Library, Web of Science, and Scopus were systematically searched to compare NLR, PLR, and LMR levels in NAFLD patients and healthy controls. Study quality was assessed using the Newcastle-Ottawa Scale, and standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated (PROSPERO registry number: CRD42024580812). A total of 20 studies were included in the meta-analysis. Results indicated that NAFLD patients had significantly higher NLR levels (SMD = 0.43; 95% CI 0.28-0.58; p < 0.001) and lower PLR levels (SMD = - 0.29; 95% CI - 0.41 to - 0.17; p < 0.001) compared to controls. However, no significant difference in LMR was observed between NAFLD patients and controls(SMD = 0.08; 95% CI - 0.00 to 0.17; p = 0.051). These findings suggest that NLR and PLR may hold promise as diagnostic markers for NAFLD, while LMR appears to have limited diagnostic utility. Further research is warranted to explore the potential role of these biomarkers in tracking disease progression.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"39"},"PeriodicalIF":3.2,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11735594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982965","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}
Qiuping Deng, Xiuju Yao, Siyun Fang, Yueshan Sun, Lei Liu, Chao Li, Guangquan Li, Yuanbiao Guo, Jinbo Liu
{"title":"Mast cell-mediated microRNA functioning in immune regulation and disease pathophysiology.","authors":"Qiuping Deng, Xiuju Yao, Siyun Fang, Yueshan Sun, Lei Liu, Chao Li, Guangquan Li, Yuanbiao Guo, Jinbo Liu","doi":"10.1007/s10238-024-01554-2","DOIUrl":"10.1007/s10238-024-01554-2","url":null,"abstract":"<p><p>Upon stimulation and activation, mast cells (MCs) release soluble mediators, including histamine, proteases, and cytokines. These mediators are often stored within cytoplasmic granules in MCs and may be released in a granulated form. The secretion of cytokines and chemokines occurs within hours following activation, with the potential to result in chronic inflammation. In addition to their role in allergic inflammation, MCs are components of the tumor microenvironment (TME). MicroRNAs (miRNAs) are small RNA molecules that do not encode proteins, but regulate post-transcriptional gene expression by binding to the 3' non-coding regions of mRNAs. This plays a crucial role in the function of MC, including the key processes of MC proliferation, maturation, apoptosis, and activation. It has been demonstrated that miRNAs are also present in extracellular vesicles (EVs) secreted by MCs. EVs derived from MCs mediate intercellular communication by carrying miRNAs, affecting various diseases including allergic diseases, intestinal disorders, neuroinflammation, and tumors. These findings provide important insights into the therapeutic mechanisms and targets of miRNAs in MCs that affect diseases. This review discusses the relevance of miRNA production by MCs in regulating their own activity and the effect of miRNAs putatively produced by other cells in the control of MC activity and their participation in selected pathologies.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"38"},"PeriodicalIF":3.2,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11735496/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982964","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}
Maha Elsabaawy, Madiha Naguib, Ahmed Abuamer, Ahmed Shaban
{"title":"Comparative application of MAFLD and MASLD diagnostic criteria on NAFLD patients: insights from a single-center cohort.","authors":"Maha Elsabaawy, Madiha Naguib, Ahmed Abuamer, Ahmed Shaban","doi":"10.1007/s10238-024-01553-3","DOIUrl":"10.1007/s10238-024-01553-3","url":null,"abstract":"<p><p>The diagnostic criteria for Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) and Metabolic Associated Steatotic Liver Disease (MASLD) aim to refine the classification of fatty liver diseases previously grouped under Non-Alcoholic Fatty Liver Disease (NAFLD). This study evaluates the applicability of the MAFLD and MASLD frameworks in NAFLD patients, exploring their clinical utility in identifying high-risk patients. A total of 369 NAFLD patients were assessed using MAFLD and MASLD diagnostic criteria. Baseline characteristics, metabolic profiles, hepatic fibrosis, and cardiovascular risks were compared across the groups. Among NAFLD patients, 97.55% (n = 359) met MASLD criteria, and 97.01% (n = 357) fulfilled MAFLD criteria. Both frameworks MAFLD and MASLD captured overlapping populations, with MASLD encompassing slightly more cases. No significant differences were observed in metabolic risk factors, fibrosis indices (APRI, FIB-4, NAFLD fibrosis score), or cardiovascular risk (10-year ASCVD score). A small subset of lean NAFLD patients (10 cases) with distinct profiles remained uncategorized by either framework. Pure NAFLD cases (n = 10) were with mild insulin resistance (HOMA-IR: 3.07 ± 0.33) and slightly elevated LDL (102.5 ± 42.87 mg/dL), while fibrosis indices indicated low fibrosis risk. Steatosis indices supported the diagnosis of early-stage NAFLD with preserved liver function. These patients do not meet the criteria for inclusion in the MAFLD or MASLD frameworks, highlighting a gap in the current diagnostic systems. MAFLD and MASLD criteria align closely with NAFLD in capturing patients with metabolic risk with MASLD-enhanced inclusivity. Further refinement is required to address heterogeneity, particularly in lean NAFLD patients. Hypertension prevalence was comparable (17.4% in NAFLD, 18.2% in MAFLD, 17.8% in MASLD; p = 0.960), as was diabetes mellitus (36.7%, 37.8%, and 37.6%, respectively; p = 0.945). Body mass index was also similar across groups, with medians of 33.25, 33.6, and 33.4 kg/m<sup>2</sup> (p = 0.731). Non-invasive markers of hepatic fibrosis, including APRI, FIB-4, and NAFLD fibrosis scores, did not differ significantly, with median FIB-4 scores around 1.05 (p = 0.953). Similarly, were the results of hepatic steatosis index and ASCVD score.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"36"},"PeriodicalIF":3.2,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977979","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}
Yang Liu, Yu Zhao, Bo Li, Xiaomin Chen, Hao Xiong, Chunlan Huang
{"title":"Decreased STING predicts adverse efficacy in bortezomib regimens and poor survival in multiple myeloma.","authors":"Yang Liu, Yu Zhao, Bo Li, Xiaomin Chen, Hao Xiong, Chunlan Huang","doi":"10.1007/s10238-025-01561-x","DOIUrl":"10.1007/s10238-025-01561-x","url":null,"abstract":"<p><strong>Purpose: </strong>STING (stimulator of interferon genes) is involved in viral and bacterial defense through interferon pathway and innate immunity. Increased susceptibility to infection is a common manifestation of multiple myeloma (MM). Thus, we aimed to explore the clinical significance and possible mechanism of STING in MM.</p><p><strong>Materials and methods: </strong>Immunohistochemistry and qPCR were used to detect STING expression in the bone marrow of MM patients, and flow cytometry was used to detect the amount of intracellular STING. All data were analyzed with clinical characteristics.</p><p><strong>Results: </strong>STING expression was remarkably reduced in MM tissues compared to normal tissues and was not associated with stage. Multivariate analysis identified STING as an independent prognostic factor in MM patients (P = 0.001). In the bortezomib-containing regimens, patients with low STING expression were more difficult to achieve remission. A model incorporating STING and m-SMART significantly improved the predictive accuracy of overall survival in bortezomib regimens (AUC, 0.511 to 0.630, P = 0.044). Bortezomib efficacy has been reported to correlate with activated immunity, but the low expression group manifested as immune apathy. Although baseline characteristics showed intergroup differences in infection, the low expression group had an increased proportion of bacterial infections (1.7-fold) and a prolonged duration of antibiotic/antifungal medication (3.55 additional days); these patients were accompanied by a decreased neutrophil-to-lymphocyte ratio (NLR) and rarely activated neutrophils and leukocytes. The intracellular STING ratio was also defective in neutrophil-dominated leukocytes.</p><p><strong>Conclusion: </strong>Our study revealed that STING had a strong association with bortezomib and could serve as a potential target for immunotherapy in multiple myeloma.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"37"},"PeriodicalIF":3.2,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732914/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982870","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}
Iman Adel, Heba A Mahmoud, Amira Ismail Khater, Fatma S Hafez
{"title":"Diagnostic value of glypican-1; a new marker differentiating pulmonary squamous cell carcinoma from adenocarcinoma: immunohistochemical study on Egyptian series.","authors":"Iman Adel, Heba A Mahmoud, Amira Ismail Khater, Fatma S Hafez","doi":"10.1007/s10238-024-01551-5","DOIUrl":"10.1007/s10238-024-01551-5","url":null,"abstract":"<p><p>Lung cancer is one of the major causes of cancer morbidity and mortality. Subtyping of non-small cell lung cancer is necessary owing to different treatment options. This study is to evaluate the value of immunohistochemical expression of glypican-1 in the diagnosis of lung squamous cell carcinoma (SCC). This retrospective study included a total of 68 cases, of which 36 were diagnosed as SCC and 32 as adenocarcinoma (ADC). Furthermore, glypican-1 expression was compared with the expressions of p63, thyroid transcription factor-1 (TTF-1), and napsin A. All cases of SCC except one showed positive immunostaining to glypican-1; 35/36 (97.2%) cases, and predominantly scored 3 + . While only 5 cases of ADC showed positive immunostaining to glypican-1, having a score of 1 + or 2 + . The difference between glypican-1 expression of the two tumor types was highly significant (p value < 0.001). The sensitivity, specificity, and overall accuracy of glypican-1 expression for differentiating lung SCC from ADC were 97.2%, 84.4%, and 91.2%, respectively. The sensitivity of glypican-1 is more than p63 in the diagnosis of lung SCC. Glypican-1 can be added as a new diagnostic marker to help in the accurate discrimination between poorly differentiated lung SCC and solid predominant adenocarcinoma cases.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"35"},"PeriodicalIF":3.2,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11724789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142963953","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}