Molecular Diagnosis & Therapy最新文献

{"title":"Blood Biomarkers of Long COVID: A Systematic Review.","authors":"Callum Thomas, Mark A Faghy, Corinna Chidley, Bethan E Phillips, Thomas Bewick, Ruth E Ashton","doi":"10.1007/s40291-024-00731-z","DOIUrl":"10.1007/s40291-024-00731-z","url":null,"abstract":"<p><strong>Background: </strong>Long coronavirus disease (COVID; LC) affects millions of people worldwide. The exact mechanisms which result in a broad, undulating and detrimental symptom profile remain unknown. Blood biomarkers associated with LC have been described; however, consensus on these remains elusive, in part due to a lack of continuity between studies on a universally accepted definition of LC. This systematic review aimed to consolidate current knowledge of blood biomarkers associated with the prevalence of LC on the basis of the World Health Organisation (WHO) clinical definition of this condition.</p><p><strong>Eligibility criteria for selecting studies: </strong>Observational, cross-sectional, and randomised control studies published in the English language that studied blood biomarkers associated with the WHO definition of LC. All studies included participants who were ≥ 18 years old and group sizes ≥ 10 participants, and were compared against a control group without any known co-morbidities.</p><p><strong>Methods: </strong>A systematic literature search was conducted according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and prospectively registered on Prospero (ID: CRD42022373121). The Cochrane, Embase, PubMed and Web of Science databases were searched from inception to January 2024. Search results were gathered using Rayyan software and data extracted using Microsoft Excel. The reporting recommendations for tumour markers prognostic studies (REMARK) questionnaire was used to assess the quality of the included studies.</p><p><strong>Results: </strong>A total of 45 observational and one interventional study comprising 4415 participants were included in this review which identified 525 blood biomarkers thought to be associated with LC. Three blood biomarker subtypes were associated with the development of LC: (1) immunological and inflammatory dysfunction, (2) endothelial/vascular dysfunction and (3) metabolic and clotting abnormalities.</p><p><strong>Discussion and conclusions: </strong>Our data are consistent with previous findings; however, no single biomarker was sufficiently associated with LC prevalence and instead a profile of biomarkers across various physiological systems may be more clinically useful. In all, 196 studies were excluded due to a lack of an adequately healthy comparator group and/or failure to meet the WHO LC definition. This demonstrates a need for further research incorporating a universal LC definition across all disease severity groups and symptom profiles, and longitudinal data reflecting the relapsing and remitting nature of this condition. Further investigation into blood biomarkers of LC, including clear reporting of healthy comparator groups and the investigation of acute and chronic biomarker changes, within the context of medical practice, may support the development of curative/restorative approaches.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"537-574"},"PeriodicalIF":4.1,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141894735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is the Homologous Recombination Repair Mutation Defined by a 15-Gene Panel Associated with the Prognosis of Epithelial Ovarian Cancer?","authors":"Yi Liu, Xiaojun Chen, Huaiwu Lu, Xin Wu, Xuehan Liu, Fei Xu, Dongdong Ye, Bo Ding, Xiaoyan Lu, Ling Qiu, Jing Zhu, Yingying Wang, Xinya Huang, Zhen Shen, Tao Zhu, Yang Shen, Ying Zhou","doi":"10.1007/s40291-024-00726-w","DOIUrl":"10.1007/s40291-024-00726-w","url":null,"abstract":"<p><strong>Background: </strong>There is no consensus regarding the specific genes included in the homologous recombination repair (HRR) gene panel for identifying the HRR deficiency (HRD) status and predicting the prognosis of epithelial ovarian cancer (EOC) patients.</p><p><strong>Objective: </strong>We aimed to explore a 15-gene panel involving the HRR pathway as a predictive prognostic indicator in Chinese patients newly diagnosed with EOC.</p><p><strong>Patients and methods: </strong>We reviewed the previously published reports about different HRR gene panels and prespecified the 15-gene panel. The genetic testing results in a 15-gene panel from 308 EOC patients diagnosed between 2014 and 2022 from six centers were collected. The association of clinicopathologic characteristics, the use of poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPis) and progression-free survival (PFS) with 15-gene panel HRR mutations (HRRm) status was assessed.</p><p><strong>Results: </strong>43.2% (133/308) of patients were determined to carry 144 deleterious HRRm, among which 68.1% (98/144) were germline mutations and 32.8% (101/308) were BRCA1/2 gene lethal mutations. The hazard ratio (HR) (95% confidence interval, CI) for PFS (HRRm v HRR wild type, HRRwt) using the 15-gene panel HRRm was 0.42 (0.28-0.64) at all stages and 0.42 (0.27-0.65) at stages IIIC-IV. However, a prognostic difference was observed only between the BRCA mutation group and the HRRwt group, not between the non-BRCA HRRm group and the HRRwt group. For the subgroups of patients not using PARPis, the HR (95% CI) was 0.41 (0.24-0.68) at stages IIIC-IV.</p><p><strong>Conclusions: </strong>This study provides evidence that 15-gene panel HRRm can predict the prognosis of EOC, of these only the BRCA1/2 mutations, not non-BRCA HRRm, contribute to prognosis prediction. Among patients without PARPis, the HRRm group presented a better PFS. This is the first study of this kind in the Chinese population.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"621-632"},"PeriodicalIF":4.1,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141535771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tracking the Plasma C-Terminal Agrin Fragment as a Biomarker of Neuromuscular Decline in 18- to 87-Year-Old Men.","authors":"Rizwan Qaisar, Asima Karim, M Shahid Iqbal, Firdos Ahmad, M Azhar Hussain","doi":"10.1007/s40291-024-00724-y","DOIUrl":"10.1007/s40291-024-00724-y","url":null,"abstract":"<p><strong>Objectives: </strong>Plasma C-terminal agrin-fragment-22 (CAF22), a breakdown product of neuromuscular junction, is a potential biomarker of muscle loss. However, its levels from adolescence to octogenarians are unknown.</p><p><strong>Methods: </strong>We evaluated young (18-34 years, n = 203), middle-aged (35-59 years, n = 163), and old men (60-87 years, n = 143) for CAF22, handgrip strength (HGS), appendicular skeletal-mass index (ASMI), and gait speed.</p><p><strong>Results: </strong>We found an age-associated increase in CAF22 from young (100.9 ± 29 pmol) to middle-aged (128.3 ± 38.7 pmol) and older men (171.5 ± 35.5 pmol) (all p<0.05). This was accompanied by a gradual reduction in HGS (37.7 ± 6.1 kg, 30.2 ± 5.2 kg, and 26.6 ± 4.7 kg, for young, middle-aged, and old men, respectively), ASMI (8.02 ± 1.02 kg/m², 7.65 ± 0.92 kg/m², 6.87 ± 0.93 kg/m², for young, middle-aged, and old men, respectively), and gait speed (1.29 ± 0.24 m/s, 1.05 ± 0.16 m/s, and 0.81 ± 0.13 m/s, for young, middle-aged, and old men, respectively). After adjustment for age, we found negative regressions of CAF22 with HGS (- 0.0574, p < 0.001) and gait speed (- 0.0162, p < 0.001) in the cumulative cohort. The receiver operating characteristics analysis revealed significant efficacy of plasma CAF22 in diagnosing muscle weakness (HGS < 27 kg) (middle-aged men; AUC = 0.731, 95% CI = 0.629-0.831, p < 0.001, Older men; AUC = 0.816, 95% CI = 0.761-0.833, p < 0.001), and low gait speed (0.8 m/s) (middle-aged men; AUC = 0.737, 95% CI = 0.602-0.871, p < 0.001, older men; AUC = 0.829, 95% CI = 0.772-0.886, p < 0.001), and a modest efficacy in diagnosing sarcopenia (middle-aged men; AUC = 0.701, 95% CI = 0.536-0.865, p = 0.032, older men; AUC = 0.822, 95% CI = 0.759-0.884, p < 0.001) in middle-aged and older men.</p><p><strong>Conclusion: </strong>Altogether, CAF22 increases with advancing age and may be a reliable marker of muscle weakness and low gait speed.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"611-620"},"PeriodicalIF":4.1,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Validity and Utility of Circulating Tumor DNA (ctDNA) Testing in Advanced Non-small Cell Lung Cancer (aNSCLC): A Systematic Literature Review and Meta-analysis.","authors":"Cheng Chen, Michael P Douglas, Meera V Ragavan, Kathryn A Phillips, Jeroen P Jansen","doi":"10.1007/s40291-024-00725-x","DOIUrl":"10.1007/s40291-024-00725-x","url":null,"abstract":"<p><strong>Purpose: </strong>Circulating tumor DNA (ctDNA) testing has become a promising tool to guide first-line (1L) targeted treatment for advanced non-small cell lung cancer (aNSCLC). This study aims to estimate the clinical validity (CV) and clinical utility (CU) of ctDNA-based next-generation sequencing (NGS) for oncogenic driver mutations to inform 1L treatment decisions in aNSCLC through a systematic literature review and meta-analysis.</p><p><strong>Methods: </strong>A systematic literature search was conducted in PubMed/MEDLINE and Embase to identify randomized control trials or observational studies reporting CV/CU on ctDNA testing in patients with aNSCLC. Meta-analyses were performed using bivariate random-effects models to estimate pooled sensitivity and specificity. Progression-free/overall survival (PFS/OS) was summarized for CU studies.</p><p><strong>Results: </strong>A total of 20 studies were identified: 17 CV only, 2 CU only, and 1 both, and 13 studies were included for the meta-analysis on multi-gene detection. The overall sensitivity and specificity for ctDNA detection of any mutation were 0.69 (95% CI 0.63-0.74) and 0.99 (95% CI 0.97-1.00), respectively. However, sensitivity varied greatly by driver gene, ranging from 0.29 (95% CI 0.13-0.53) for ROS1 to 0.77 (95% CI 0.63-0.86) for KRAS. Two studies that compared PFS with ctDNA versus tissue-based testing followed by 1L targeted therapy found no significant differences. One study reported OS curves on ctDNA-matched and tissue-matched therapies but no hazard ratios were provided.</p><p><strong>Conclusions: </strong>ctDNA testing demonstrated an overall acceptable diagnostic accuracy in patients with aNSCLC, however, sensitivity varied greatly by driver mutation. Further research is needed, especially for uncommon driver mutations, to better understand the CU of ctDNA testing in guiding targeted treatments for aNSCLC.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"525-536"},"PeriodicalIF":4.1,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11349784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141876516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Author reply to Wang et al.: \"The Diagnostic and Prognostic Value of miR-155 in Cancers: An Updated Meta‑analysis\".","authors":"Yanan Wu, Lubanga Nasifu, Bangshun He","doi":"10.1007/s40291-024-00711-3","DOIUrl":"10.1007/s40291-024-00711-3","url":null,"abstract":"","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"509-511"},"PeriodicalIF":4.1,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141080901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic Accuracy of Exosomal Long Noncoding RNAs in Diagnosis of NSCLC: A Meta-Analysis.","authors":"Xiaodong Song, Linlin Duan, Yongshuai Dong","doi":"10.1007/s40291-024-00715-z","DOIUrl":"10.1007/s40291-024-00715-z","url":null,"abstract":"<p><strong>Purpose: </strong>Globally, non-small cell lung cancer (NSCLC) is the primary cause of cancer-related mortality, both early and accurate diagnosis are essential for effective treatment and improved patient outcomes. Exosomal noncoding RNAs (ncRNAs) have emerged as promising biomarkers for NSCLC diagnosis. This meta-analysis aims to assess the diagnostic accuracy of exosomal long noncoding RNAs (lncRNAs) for diagnosing NSCLC.</p><p><strong>Methods: </strong>A comprehensive literature search was conducted to identify relevant studies that assessed the diagnostic performance of exosomal lncRNAs in NSCLC. Quality assessment and data extraction were performed independently by two reviewers. Pooled sensitivity, specificity, and other relevant diagnostic parameters were calculated using a bivariate random-effects model. Subgroup analyses and meta-regression were conducted to explore potential sources of heterogeneity.</p><p><strong>Results: </strong>Sixteen studies, comprising 1843 NSCLC cases and 1298 controls, were included in this meta-analysis. The pooled sensitivity and specificity of nine exosomal lncRNAs for diagnosing NSCLC were 0.74 [95% confidence interval (CI) 0.69-0.79] and 0.78 (95% CI 0.68-0.85). The pooled area under the receiver operating characteristic curve (AUC) for fifteen lncRNAs was 0.80 (95% CI 0.768-0.831). Meta-regression could not find any source for interstudy heterogeneity.</p><p><strong>Conclusion: </strong>Exosomal lncRNAs, particularly AL139294.1, GAS5, LUCAT1, and SOX2-OT, have excellent diagnostic accuracy and promising diagnostic potential in NSCLC. Therefore, they can be used as diagnostic tools for early detection of NSCLC.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"455-468"},"PeriodicalIF":4.1,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141248735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond Death: Unmasking the Intricacies of Apoptosis Escape.","authors":"Sercan Ergün, Senanur Aslan, Dilbeste Demir, Sümeyye Kayaoğlu, Mevsim Saydam, Yeda Keleş, Damla Kolcuoğlu, Neslihan Taşkurt Hekim, Sezgin Güneş","doi":"10.1007/s40291-024-00718-w","DOIUrl":"10.1007/s40291-024-00718-w","url":null,"abstract":"<p><p>Apoptosis, or programmed cell death, maintains tissue homeostasis by eliminating damaged or unnecessary cells. However, cells can evade this process, contributing to conditions such as cancer. Escape mechanisms include anoikis, mitochondrial DNA depletion, cellular FLICE inhibitory protein (c-FLIP), endosomal sorting complexes required for transport (ESCRT), mitotic slippage, anastasis, and blebbishield formation. Anoikis, triggered by cell detachment from the extracellular matrix, is pivotal in cancer research due to its role in cellular survival and metastasis. Mitochondrial DNA depletion, associated with cellular dysfunction and diseases such as breast and prostate cancer, links to apoptosis resistance. The c-FLIP protein family, notably CFLAR, regulates cell death processes as a truncated caspase-8 form. The ESCRT complex aids apoptosis evasion by repairing intracellular damage through increased Ca2+ levels. Antimitotic agents induce mitotic arrest in cancer treatment but can lead to mitotic slippage and tetraploid cell formation. Anastasis allows cells to resist apoptosis induced by various triggers. Blebbishield formation suppresses apoptosis indirectly in cancer stem cells by transforming apoptotic cells into blebbishields. In conclusion, the future of apoptosis research offers exciting possibilities for innovative therapeutic approaches, enhanced diagnostic tools, and a deeper understanding of the complex biological processes that govern cell fate. Collaborative efforts across disciplines, including molecular biology, genetics, immunology, and bioinformatics, will be essential to realize these prospects and improve patient outcomes in diverse disease contexts.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"403-423"},"PeriodicalIF":4.1,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11211167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Talicabtagene Autoleucel: First Approval.","authors":"Tina Nie","doi":"10.1007/s40291-024-00719-9","DOIUrl":"10.1007/s40291-024-00719-9","url":null,"abstract":"<p><p>Talicabtagene autoleucel (NexCAR19™) is a chimeric antigen receptor (CAR) T-cell therapy being developed by the Indian Institute of Technology, Bombay (IIT-B) and Immunoadoptive Cell Therapy (ImmunoACT) for the treatment of relapsed/refractory B-cell malignancies. Talicabtagene autoleucel contains autologous T cells from the patient, which have been modified to express a humanized anti-CD19 CAR that targets B cells. A single intravenous dose of talicabtagene autoleucel was associated with high response rates in pooled results from a phase I and phase II trial in patients with relapsed/refractory B-cell malignancies. Talicabtagene autoleucel was approved in India for the treatment of relapsed/refractory B-cell lymphomas and relapsed/refractory B-cell acute lymphoblastic leukaemia on 13 October 2023. This article summarizes the milestones in the development of talicabtagene autoleucel leading to this first approval for relapsed/refractory B-cell lymphomas and relapsed/refractory B-cell acute lymphoblastic leukaemia.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"495-499"},"PeriodicalIF":4.1,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141080986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Role of HtrA Family Genes in Cancer: A Systematic Review.","authors":"Monika Anna Rosochowicz, Katarzyna Kulcenty, Wiktoria Maria Suchorska","doi":"10.1007/s40291-024-00712-2","DOIUrl":"10.1007/s40291-024-00712-2","url":null,"abstract":"<p><strong>Purpose: </strong>HtrA1, HtrA2, HtrA3 and HtrA4 appear to be involved in the development of pathologies such as cancer. This systematic review reports the results of a literature search performed to compare the expression of HtrA family genes and proteins in cancer versus non-cancer tissues and cell lines, assess relationships between HtrA expression and cancer clinical features in cancer, and analyse the molecular mechanism, by which HtrA family affects cancer.</p><p><strong>Methods: </strong>The literature search was conducted according to the PRISMA statement among four databases (PubMed, Web of Science, Embase and Scopus).</p><p><strong>Results: </strong>A total of 38 articles met the inclusion criteria and involved the expression of HtrA family members and concerned the effect of HtrA expression on cancer and metastasis development or on the factor that influences it. Additionally, 31 reports were retrieved manually. Most articles highlighted that HtrA1 and HtrA3 exhibited tumour suppressor activity, while HtrA2 was associated with tumour growth and metastasis. There were too few studies to clearly define the role of the HtrA4 protease in tumours.</p><p><strong>Conclusion: </strong>Although the expression of serine proteases of the HtrA family was dependent on tumour type, stage and the presence of metastases, most articles indicated that HtrA1 and HtrA3 expression in tumours was downregulated compared with healthy tissue or cell lines. The expression of HtrA2 was completely study dependent. The limited number of studies on HtrA4 expression made it impossible to draw conclusions about differences in expression between healthy and tumour tissue. The conclusions drawn from the study suggest that HtrA1 and HtrA3 act as tumour suppressors.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"347-377"},"PeriodicalIF":4.1,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11211202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140877819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding Molecular Mechanisms Underlying Outcomes After Ischemic Stroke Thrombectomy by RNA Sequencing of Retrieved Clots.","authors":"Briana A Santo, Kerry E Poppenberg, Shiau-Sing Ciecierska, Jaims Lim, Ammad A Baig, Vinay Jaikumar, Kunal P Raygor, Tatsat R Patel, Munjal Shah, Elad I Levy, Adnan H Siddiqui, Vincent M Tutino","doi":"10.1007/s40291-024-00716-y","DOIUrl":"10.1007/s40291-024-00716-y","url":null,"abstract":"<p><strong>Background: </strong>Transcriptomic profiling has emerged as a powerful tool for exploring the molecular landscape of ischemic stroke clots and providing insights into the pathophysiological mechanisms underlying stroke progression and recovery. In this study, we aimed to investigate the relationship between stroke clot transcriptomes and stroke thrombectomy outcome, as measured by early neurological improvement (ENI) 30 (i.e., a 30% reduction in NIHSS at 24 h post-thrombectomy).</p><p><strong>Hypothesis: </strong>We hypothesized that there exist distinct clot gene expression patterns between good and poor neurological outcomes.</p><p><strong>Methods: </strong>Transcriptomic analysis of 32 stroke clots retrieved by mechanical thrombectomy was conducted. Transcriptome data of these clots were analyzed to identify differentially expressed genes (DEGs), defined as those with a log(fold-change) ≥ 1.5 and q < 0.05 between samples with good and poor early neurological outcomes. Gene ontology and bioinformatics analyses were performed on genes with p < 0.01 to identify enriched biological processes and Ingenuity Pathway Analysis canonical pathways. Moreover, AUC analysis assessed the predictive power of DEGs for 90-day function outcome (mRS ≤ 2) and cellular composition of clot was predicted using CIBERSORT. We also assessed whether differential enrichment of immune cell types could indicate patient survival.</p><p><strong>Results: </strong>A total of 41 DEGs were identified. Bioinformatics showed that enriched biological processes and pathways emphasized the chronic immune response and matrix metalloproteinase inhibition. Moreover, 25 of the DEGs were found to be significant predictors of 90-day mRS. These genes were indicative of monocytes enrichment and neutrophil depletion in patients with poorer outcomes.</p><p><strong>Conclusion: </strong>Our study revealed a distinct gene expression pattern and dysregulated biological pathways associated with ENI. This expression pattern was also predictive of long-term outcome, suggesting a biological link between those ENIs and 90-day mRS.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"469-477"},"PeriodicalIF":4.1,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141072126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}