Biomarker Research最新文献

{"title":"Tumor microenvironment and immunotherapy for triple-negative breast cancer.","authors":"Zijie Guo, Ziyu Zhu, Xixi Lin, Shenkangle Wang, Yihong Wen, Linbo Wang, Lili Zhi, Jichun Zhou","doi":"10.1186/s40364-024-00714-6","DOIUrl":"10.1186/s40364-024-00714-6","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) is a subtype of breast cancer known for its high aggressiveness and poor prognosis. Conventional treatment of TNBC is challenging due to its heterogeneity and lack of clear targets. Recent advancements in immunotherapy have shown promise in treating TNBC, with immune checkpoint therapy playing a significant role in comprehensive treatment plans. The tumor microenvironment (TME), comprising immune cells, stromal cells, and various cytokines, plays a crucial role in TNBC progression and response to immunotherapy. The high presence of tumor-infiltrating lymphocytes and immune checkpoint proteins in TNBC indicates the potential of immunotherapeutic strategies. However, the complexity of the TME, while offering therapeutic targets, requires further exploration of its multiple roles in immunotherapy. In this review, we discuss the interaction mechanism between TME and TNBC immunotherapy based on the characteristics and composition of TME, and elaborate on and analyze the effect of TME on immunotherapy, the potential of TME as an immune target, and the ability of TME as a biomarker. Understanding these dynamics will offer new insights for enhancing therapeutic approaches and investigating stratification and prognostic markers for TNBC patients.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"12 1","pages":"166"},"PeriodicalIF":9.5,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11689763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights into genetic aberrations and signalling pathway interactions in chronic lymphocytic leukemia: from pathogenesis to treatment strategies.","authors":"Anna Sobczyńska-Konefał, Monika Jasek, Lidia Karabon, Emilia Jaskuła","doi":"10.1186/s40364-024-00710-w","DOIUrl":"10.1186/s40364-024-00710-w","url":null,"abstract":"<p><p>Chronic lymphocytic leukemia (CLL) is prevalent in adults and is characterized by the accumulation of mature B cells in the blood, bone marrow, lymph nodes, and spleens. Recent progress in therapy and the introduction of targeted treatments [inhibitors of Bruton's tyrosine kinase (BTKi) or inhibitor of anti-apoptotic B-cell lymphoma-2 (Bcl-2i) protein (venetoclax)] in place of chemoimmunotherapy have significantly improved the outcomes of patients with CLL. These advancements have shifted the importance of traditional predictive markers, leading to a greater focus on resistance genes and reducing the significance of mutations, such as TP53 and del(17p). Despite the significant progress in CLL treatment, some patients still experience disease relapse. This is due to the substantial heterogeneity of CLL as well as the interconnected genetic resistance mechanisms and pathway adaptive resistance mechanisms to targeted therapies in CLL. Although the knowledge of the pathomechanism of CLL has expanded significantly in recent years, the precise origins of CLL and the interplay between various genetic factors remain incompletely understood, necessitating further research. This review enhances the molecular understanding of CLL by describing how BCR signalling, NF-κB PI3K/AKT, and ROR1 pathways sustain CLL cell survival, proliferation, and resistance to apoptosis. It also presents genetic and pathway-adaptive resistance mechanisms in CLL. Identifying B-cell receptor (BCR) signalling as a pivotal driver of CLL progression, the findings advocate personalized treatment strategies based on molecular profiling, emphasizing the need for further research to unravel the complex interplay between BCR signalling and its associated pathways to improve patient outcomes.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"12 1","pages":"162"},"PeriodicalIF":9.5,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11682641/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunophenotypic analysis on circulating T cells for early diagnosis of lung cancer.","authors":"Sung-Woo Lee, Young Ju Kim, Kyung Na Rho, Saei Jeong, Jeong Eun Noh, Hee-Ok Kim, Hyun-Ju Cho, Ju Sik Yun, In-Jae Oh, Jae-Ho Cho","doi":"10.1186/s40364-024-00713-7","DOIUrl":"10.1186/s40364-024-00713-7","url":null,"abstract":"<p><p>The immune system continuously interacts with tumors, possibly leading to systemic alterations in circulating immune cells. However, the potential of these cancer-associated changes for diagnostic purposes remains poorly explored. To investigate this, we conducted a comprehensive flow cytometric analysis of 452 peripheral blood mononuclear cell (PBMC) samples from 206 non-small-cell lung cancer (NSCLC) patients, 100 small-cell lung cancer (SCLC) patients, 94 healthy individuals, and 52 benign lung disease (BLD) patients. We focused specifically on circulating T cells, given their close interaction with tumors, and initially assessed 93 T-cell features from the flow cytometric analysis. Using a feature selection protocol, we identified five T-cell features in peripheral blood with strong diagnostic relevance. Notably, while individual alterations in these features lacked cancer specificity, simultaneous alterations were uniquely indicative of lung cancer. To comprehensively analyze these features, we developed a scoring model, \"IMmunoPhenotypic Analysis for Cancer deTection (IMPACT).\" Comprehensive analysis using the five features (IMPACT-5) demonstrated high cancer specificity and biomarker efficacy, as evidenced by the high area under the receiver operating characteristic curve values for lung cancer patients (0.9187, 0.9277, and 0.9363 for stage I NSCLC, stage IV NSCLC, and SCLC patients, respectively), in stark contrast to BLD patients (0.5212). These findings suggest that comprehensive analysis of cancer-associated changes in circulating T cells can effectively detect lung cancer from its early stages, proposing immunophenotypic analysis of circulating T cells as an innovative liquid biopsy-based diagnostic biomarker.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"12 1","pages":"161"},"PeriodicalIF":9.5,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11674110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding burn trauma: biomarkers for early diagnosis of burn-induced pathologies.","authors":"Fadi Khalaf, Daniella Touma, Alexandra Pappas, Lareina Hatim, Stephanie Wojtowicz-Piotrowski, Marc G Jeschke","doi":"10.1186/s40364-024-00707-5","DOIUrl":"10.1186/s40364-024-00707-5","url":null,"abstract":"<p><p>Burn injuries represent a significant global challenge due to their multifaceted nature, characterized by a complex cascade of metabolic and immune dysfunction that can result in severe complications. If not identified and managed promptly, these complications can escalate, often leading to fatal outcomes. This underscores the critical importance of timely and precise diagnosis. Fortunately, biomarkers for burn-induced pathologies and outcomes have emerged as powerful diagnostic and prognostic tools. These biomarkers enable early diagnosis and intervention, facilitate risk assessment, support patient-specific treatment, monitoring of disease progression, and therapeutic efficacy, ultimately contributing to improved patient outcomes. However, while previous studies have provided valuable biomarkers for the detection of burn-induced pathologies, many of these were constrained by the techniques and sample sizes available at the time, which can limit the generalizability of the findings. This review highlights numerous biomarkers studied in the literature to date, underscoring the need to replicate these findings in more diverse and representative populations. It also emphasizes the importance of advancing research efforts to develop more efficient, accurate, and cost-effective approaches for integrating biomarkers into clinical practice.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"12 1","pages":"160"},"PeriodicalIF":9.5,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The LILRB family in hematologic malignancies: prognostic associations, mechanistic considerations, and therapeutic implications.","authors":"Alan Hodges, Rachel Dubuque, Shu-Hsia Chen, Ping-Ying Pan","doi":"10.1186/s40364-024-00705-7","DOIUrl":"10.1186/s40364-024-00705-7","url":null,"abstract":"<p><p>The leukocyte immunoglobulin-like receptor B (LILRB) proteins, characterized by their transmembrane nature and canonical immunoreceptor tyrosine-based inhibitory motifs (ITIM) signaling, play a pivotal role in maintaining immune homeostasis and are implicated in the pathogenesis of various disease states. This comprehensive review will focus on the intricate involvement of the LILRB family in hematologic malignancies. These receptors have emerged as valuable diagnostic and prognostic biomarkers in leukemia, lymphoma, and myeloma. Beyond their prognostic implications, LILRBs actively shape the immune microenvironment and directly influence the disease pathogenesis of hematologic malignancies. Furthermore, their identification as potential therapeutic targets offer a promising avenue for precision medicine strategies in the treatment of these disorders. Currently, multiple LILRB directed therapies are in the preclinical and clinical trial pipelines. This review underscores the multifaceted role of the LILRB family in hematologic malignancies, highlighting their significance from diagnostic and prognostic perspectives to their broader impact on disease pathophysiology and as valuable therapeutic targets.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"12 1","pages":"159"},"PeriodicalIF":9.5,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11658067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142856081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"mRNA cancer vaccines from bench to bedside: a new era in cancer immunotherapy.","authors":"Alireza Shariati, Pouria Khani, Farzad Nasri, Hamed Afkhami, Arya Khezrpour, Sina Kamrani, Fatemeh Shariati, Sajad Alavimanesh, Mohammad Hossein Modarressi","doi":"10.1186/s40364-024-00692-9","DOIUrl":"10.1186/s40364-024-00692-9","url":null,"abstract":"<p><p>Harnessing the power of the immune system to target cancer cells is one of the most appealing approaches for cancer therapy. Among these immunotherapies, messenger ribonucleic acid (mRNA) cancer vaccines are worthy of consideration, as they have demonstrated promising results in clinical trials. These vaccines have proven to be safe and well-tolerated. They can be easily mass-produced in a relatively short time and induce a systemic immune response effective against both the primary tumor and metastases. Transcripts encoding immunomodulatory molecules can also be incorporated into the mRNA, enhancing its efficacy. On the other hand, there are some challenges associated with their application, including mRNA instability, insufficient uptake by immune cells, and intrinsic immunogenicity, which can block mRNA translation. Many innovations have been suggested to overcome these obstacles, including structural modification (such as 5' cap modification), optimizing delivery vehicles (especially dendritic cells (DCs) and nanoparticles), and using antigens that can enhance immunogenicity by circumventing tolerance mechanisms. A popular approach is to combine mRNA cancer vaccines with traditional and novel cancer treatments like chemotherapy, radiotherapy, and immune checkpoint blockade (ICB). They are most efficacious when combined with other therapies like ICBs. There is still a long way to go before these vaccines enter the standard of care for cancer patients, but with the incredible pace of development in this field, their clinical application will soon be witnessed. This review highlights the recent advances and challenges of mRNA cancer vaccines. Finally, some of the most prominent clinical applications of these vaccines will be reviewed.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"12 1","pages":"157"},"PeriodicalIF":9.5,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11656831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142856779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"State of the art CRISPR-based strategies for cancer diagnostics and treatment.","authors":"Emma Di Carlo, Carlo Sorrentino","doi":"10.1186/s40364-024-00701-x","DOIUrl":"10.1186/s40364-024-00701-x","url":null,"abstract":"<p><p>Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technology is a groundbreaking and dynamic molecular tool for DNA and RNA \"surgery\". CRISPR/Cas9 is the most widely applied system in oncology research. It is a major advancement in genome manipulation due to its precision, efficiency, scalability and versatility compared to previous gene editing methods. It has shown great potential not only in the targeting of oncogenes or genes coding for immune checkpoint molecules, and in engineering T cells, but also in targeting epigenomic disturbances, which contribute to cancer development and progression. It has proven useful for detecting genetic mutations, enabling the large-scale screening of genes involved in tumor onset, progression and drug resistance, and in speeding up the development of highly targeted therapies tailored to the genetic and immunological profiles of the patient's tumor. Furthermore, the recently discovered Cas12 and Cas13 systems have expanded Cas9-based editing applications, providing new opportunities in the diagnosis and treatment of cancer. In addition to traditional cis-cleavage, they exhibit trans-cleavage activity, which enables their use as sensitive and specific diagnostic tools. Diagnostic platforms like DETECTR, which employs the Cas12 enzyme, that cuts single-stranded DNA reporters, and SHERLOCK, which uses Cas12, or Cas13, that specifically target and cleave single-stranded RNA, can be exploited to speed up and advance oncological diagnostics. Overall, CRISPR platform has the great potential to improve molecular diagnostics and the functionality and safety of engineered cellular medicines. Here, we will emphasize the potentially transformative impact of CRISPR technology in the field of oncology compared to traditional treatments, diagnostic and prognostic approaches, and highlight the opportunities and challenges raised by using the newly introduced CRISPR-based systems for cancer diagnosis and therapy.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"12 1","pages":"156"},"PeriodicalIF":9.5,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11657220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Exosomal PSM-E inhibits macrophage M2 polarization to suppress prostate cancer metastasis through the RACK1 signaling axis.","authors":"Xingliang Qin, Ruoxi Niu, Yongyao Tan, Yuxin Huang, Weishu Ren, Weiwei Zhou, Huiquan Wu, Junlong Zhang, Mingze Xu, Xiang Zhou, Hongyu Guan, Xun Zhu, Yu Chen, Kaiyuan Cao","doi":"10.1186/s40364-024-00708-4","DOIUrl":"10.1186/s40364-024-00708-4","url":null,"abstract":"","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"12 1","pages":"155"},"PeriodicalIF":9.5,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11657384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142856857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AXL in myeloid malignancies - an elusive target?","authors":"Pia Aehnlich, Katharina Leuchte, Claudia Schöllkopf, Sara Fresnillo Salo, Tina J Seremet, Estrid Høgdall, Özcan Met, Kirsten Grønbaek, Per Thor Straten","doi":"10.1186/s40364-024-00704-8","DOIUrl":"10.1186/s40364-024-00704-8","url":null,"abstract":"<p><p>The TAM receptor tyrosine kinase family member AXL plays critical roles in tissue homeostasis, survival, chemoresistance, and motility. This study investigates the receptor expression in six AML cell lines and bone marrow myeloblasts from 25 patients with myeloid neoplasms. We found that AXL expression was generally absent or very low in AML myeloblasts. These findings suggest that the efficacy of AXL inhibitors may not depend on AXL positivity but rather on alternative therapeutic mechanisms, such as inducing significant immune responses.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"12 1","pages":"158"},"PeriodicalIF":9.5,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11657231/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142856855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence and clinical significance of Claudin-3 expression in cancer: a tissue microarray study on 14,966 tumor samples.","authors":"Seyma Büyücek, Nina Schraps, Anne Menz, Florian Lutz, Viktoria Chirico, Florian Viehweger, David Dum, Ria Schlichter, Andrea Hinsch, Christoph Fraune, Christian Bernreuther, Martina Kluth, Claudia Hube-Magg, Katharina Möller, Viktor Reiswich, Andreas M Luebke, Patrick Lebok, Sören Weidemann, Guido Sauter, Maximilian Lennartz, Frank Jacobsen, Till S Clauditz, Andreas H Marx, Ronald Simon, Stefan Steurer, Eike Burandt, Natalia Gorbokon, Sarah Minner, Till Krech, Morton Freytag","doi":"10.1186/s40364-024-00702-w","DOIUrl":"10.1186/s40364-024-00702-w","url":null,"abstract":"<p><strong>Background: </strong>Claudin-3 (CLDN3) participates in the formation of the tight-junctions (TJs) that regulate intercellular permeability. Altered CLDN3 expression has been linked to tumor progression in multiple tumor types. Despite its widespread expression in normal epithelial cells, CLDN3 is considered an attractive drug target candidate, since it may be more accessible in cancer cells than in normal cells due to their less orchestrated cell growth.</p><p><strong>Methods: </strong>To comprehensively determine the prevalence of CLDN3 expression in cancer, a tissue microarray containing 14,966 samples from 133 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry.</p><p><strong>Results: </strong>CLDN3 immunostaining was observed in 8,479 (68.9%) of 12,314 analyzable tumors, including 11.6% with weak, 6.2% with moderate, and 51.1% with strong positivity. CLDN3 staining was found in 96 of 133 tumor categories, 80 of which contained at least one strongly positive case. CLDN3 positivity was most seen in neuroendocrine neoplasms (92-100%) and in adenocarcinomas (67-100%), tumors of the female genital tract, including various subtypes of ovarian and endometrial carcinoma (up to 100%), as well as different subtypes of breast cancer (95.3-100%). CLDN3 positivity was less common in squamous cell carcinomas (0-43.2%) and mainly absent in melanoma, mesenchymal, and hematolymphatic neoplasms. In clear cell renal cell carcinoma (ccRCC), low CLDN3 was strongly linked to poor ISUP (p < 0.0001), Fuhrman (p < 0.0001), and Thoenes (p < 0.0001) grades, advanced pT category (p < 0.0001), high UICC stage (p = 0.0006) and distant metastasis (p = 0.0011), as well as shortened overall (p = 0.0118) and recurrence-free (p < 0.0001) survival. In papillary RCC (pRCC), low CLDN3 was associated with poor grade (p < 0.05), high pT (p = 0.0273) and distant metastasis (p = 0.0357). In urothelial carcinoma high CLDN3 was linked to high grade (p < 0.0001) and nodal metastasis (p = 0.0111). The level of CLDN3 staining was unrelated to parameters of tumor aggressiveness in pancreatic, gastric, and breast cancer.</p><p><strong>Conclusion: </strong>In conclusion, our data demonstrate significant levels of CLDN3 expression in many different tumor entities and identify reduced CLDN3 expression as a potential prognostic marker in RCC.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"12 1","pages":"154"},"PeriodicalIF":9.5,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11633013/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142808604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}