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Mehta PK, Soni A, Dahiya B, Sheoran R, Nehra K, Sharma M. Quantification of MPT-64 within pleural fluid extracellular vesicles of tuberculous pleurisy patients by real-time immuno-PCR. Anal Biochem 2025; 702:115829. [PMID: 40058538 DOI: 10.1016/j.ab.2025.115829] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2025] [Revised: 03/01/2025] [Accepted: 03/05/2025] [Indexed: 03/22/2025]
Abstract
Diagnosis of tuberculous (TB) pleurisy is an exigent task owing to atypical clinical presentations and low bacillary content in clinical samples. Hence, there is a crucial need to deliberate a quick and consistent diagnostic test. We recently quantified Mycobacterium tuberculosis (Mtb)-specific MPT-64 (Rv1980c) within pleural fluid extracellular vesicles (pEVs) of TB pleurisy patients by SYBR Green real-time immuno-PCR (RT-I-PCR) assay and compared its diagnostic efficacy with respective ELISA and GeneXpert assay. The size of pEVs of TB pleurisy patients ranged between 47.7 and 170.2 nm as evaluated by Nanoparticle tracking analysis and Transmission electron microscopy. Noticeably, a dynamic range (0.7 pg/mL-9.7 ng/mL) of Mtb MPT-64 was quantitatively detected within pEVs of TB pleurisy individuals by RT-I-PCR, albeit ELISA exhibited a thin range (2.5 ng/mL-11.2 ng/mL). Our RT-I-PCR demonstrated sensitivity of 80 % and 80.9 % in clinically suspected/probable (n = 35) and total (n = 42) TB pleurisy individuals, respectively, with 97.3 % specificity in 38 non-TB controls, against a composite reference standard. Concurrently, MPT-64 detection within pEVs of clinically suspected/probable TB pleurisy cases by ELISA and GeneXpert displayed substantially lower sensitivities (p < 0.05-0.01) than RT-I-PCR. After further improving the sensitivity and authenticating these RT-I-PCR results with a larger sample size, this assay may yield a promising diagnostic kit.
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Affiliation(s)
- Promod K Mehta
- Department of Life Sciences, Faculty of Allied Health Sciences, Shree Guru Gobind Singh Tricentenary (SGT) University, Gurugram, 122505, India; Centre for Biotechnology, Maharshi Dayanand University, Rohtak, 124001, India.
| | - Aishwarya Soni
- Department of Life Sciences, Faculty of Allied Health Sciences, Shree Guru Gobind Singh Tricentenary (SGT) University, Gurugram, 122505, India; Centre for Biotechnology, Maharshi Dayanand University, Rohtak, 124001, India; Department of Biotechnology, Deenbandhu Chhotu Ram University of Science and Technology (DCRUST), Murthal, Sonipat, 131039, India
| | - Bhawna Dahiya
- Department of Life Sciences, Faculty of Allied Health Sciences, Shree Guru Gobind Singh Tricentenary (SGT) University, Gurugram, 122505, India; Centre for Biotechnology, Maharshi Dayanand University, Rohtak, 124001, India
| | - Reetu Sheoran
- School of Basic Sciences and Research, Sharda University, Greater Noida, 201301, India
| | - Kiran Nehra
- Department of Biotechnology, Deenbandhu Chhotu Ram University of Science and Technology (DCRUST), Murthal, Sonipat, 131039, India
| | - Mukesh Sharma
- Department of Medical Microbiology, Faculty of Medicine and Health Sciences, SGT University, Gurugram, 122505, India
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Shah KA, Ali T, Hussain Y, Dormocara A, You B, Cui JH. Isolation, characterization and therapeutic potentials of exosomes in lung cancer: Opportunities and challenges. Biochem Biophys Res Commun 2025; 759:151707. [PMID: 40153996 DOI: 10.1016/j.bbrc.2025.151707] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2024] [Revised: 02/08/2025] [Accepted: 03/25/2025] [Indexed: 04/01/2025]
Abstract
Lung cancer (LC) signifies the primary cause of cancer-related mortality, representing 24 % of all cancer fatalities. LC is intricate and necessitates innovative approaches for early detection, precise diagnosis, and tailored treatment. Exosomes (EXOs), a subclass of extracellular vesicles (EVs), are integral to LC advancement, intercellular communication, tumor spread, and resistance to anticancer therapies. EXOs represent a viable drug delivery strategy owing to their distinctive biological characteristics, such as natural origin, biocompatibility, stability in blood circulation, minimal immunogenicity, and potential for modification. They can function as vehicles for targeted pharmaceuticals and facilitate the advancement of targeted therapeutics. EXOs are pivotal in the metastatic cascade, facilitating communication between cancer cells and augmenting their invasive capacity. Nonetheless, obstacles such as enhancing cargo loading efficiency, addressing homogeneity concerns during preparation, and facilitating large-scale clinical translation persist. Interdisciplinary collaboration in research is crucial for enhancing the efficacy of EXOs drug delivery systems. This review explores the role of EXOs in LC, their potential as therapeutic agents, and challenges in their development, aiming to advance targeted treatments. Future research should concentrate on engineering optimization and developing innovative EXOs to improve flexibility and effectiveness in clinical applications.
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Affiliation(s)
- Kiramat Ali Shah
- College of Pharmaceutical Science, Soochow University, Renai Road 199, SIP, 215213, Suzhou, Jiangsu, China
| | - Tariq Ali
- Department of Civil and Environmental Engineering, Shantou University, Shantou, Guangdong, 515063, China
| | - Yaseen Hussain
- College of Pharmaceutical Science, Soochow University, Renai Road 199, SIP, 215213, Suzhou, Jiangsu, China
| | - Amos Dormocara
- College of Pharmaceutical Science, Soochow University, Renai Road 199, SIP, 215213, Suzhou, Jiangsu, China
| | - Bengang You
- College of Pharmaceutical Science, Soochow University, Renai Road 199, SIP, 215213, Suzhou, Jiangsu, China
| | - Jing-Hao Cui
- College of Pharmaceutical Science, Soochow University, Renai Road 199, SIP, 215213, Suzhou, Jiangsu, China.
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Qi W, Teng B, Zhang F, Chen Y, Xu J, Luan J. Clinical value of miR-200b in diagnosis and prognosis of childhood pneumonia. BMC Pediatr 2025; 25:42. [PMID: 39825267 PMCID: PMC11748587 DOI: 10.1186/s12887-024-05370-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2024] [Accepted: 12/26/2024] [Indexed: 01/20/2025] Open
Abstract
BACKGROUND Childhood pneumonia (CP) is a common respiratory infectious disease in children with high morbidity and mortality. However, differential changes in miRNAs may interact with the regulation of CP. The aim of this paper was to discuss the miR-200b expression in CP and its diagnostic and prognostic value. METHODS RT-qPCR was used to measure the miR-200b expression in venous blood. ROC curve was adopted to assess the diagnostic ability of miR-200b in children with CP. Logistic analysis was adopted to study the risk factors are related to CP. Kaplan-Meier was employed to analyze the prognostic ability of miR-200b in CP. Transfection of MRC-5 cells in vitro was used to verify the impact of miR-200b on cell proliferation and apoptosis. RESULTS The expression of miR-200b in serum of CP children was upregulated. ROC analysis prompted that upregulation of miR-200b could be effective in distinguishing between CP and healthy children. Compared with the good prognosis group, miR-200b expression was elevated in the poor prognosis group. Kaplan-Meier reminded that high expression of miR-200b led to a poor prognosis in CP. Cells experiments demonstrated that transfection with miR-200b inhibitor encouraged cell proliferation and inhibited apoptosis, whereas transfection with miR-200b mimic had the contrary result. CONCLUSIONS miR-200b had high diagnostic and prognostic value for children with CP and may become a biomarker for clinical diagnosis and prognosis. CLINICAL TRIAL NUMBER Not applicable.
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Affiliation(s)
- Weiwei Qi
- Department of Paediatrics, Xingtai People's Hospital, Xingtai, 054000, China
| | - Beibei Teng
- Department of Pediatric, Nanjing Luhe People's Hospital, NanJing, 211500, China
| | - Fan Zhang
- Department of Anesthesiology, Children's Hospital of Fudan University, Shanghai, 201102, China
| | - Ying Chen
- Department of Pediatrics, Bethune International Peace Hospital, Shijiazhuang, 050051, China
| | - Jinmei Xu
- Department of Pediatrics, Affiliated Hospital of Yangzhou University, No. 45, Taizhou Road, Guangling District, Yangzhou, 225000, China.
| | - Jinling Luan
- Department of Pediatrics, Tongde Hospital of Zhejiang Province, No. 234, Gucui Road, Hangzhou, 310000, China.
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Vasu S, Johnson V, M A, Reddy KA, Sukumar UK. Circulating Extracellular Vesicles as Promising Biomarkers for Precession Diagnostics: A Perspective on Lung Cancer. ACS Biomater Sci Eng 2025; 11:95-134. [PMID: 39636879 DOI: 10.1021/acsbiomaterials.4c01323] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/07/2024]
Abstract
Extracellular vesicles (EVs) have emerged as promising biomarkers in liquid biopsy, owing to their ubiquitous presence in bodily fluids and their ability to carry disease-related cargo. Recognizing their significance in disease diagnosis and treatment, substantial efforts have been dedicated to developing efficient methods for EV isolation, detection, and analysis. EVs, heterogeneous membrane-encapsulated vesicles secreted by all cells, contain bioactive substances capable of modulating recipient cell biology upon internalization, including proteins, lipids, DNA, and various RNAs. Their prevalence across bodily fluids has positioned them as pivotal mediators in physiological and pathological processes, notably in cancer, where they hold potential as straightforward tumor biomarkers. This review offers a comprehensive examination of advanced nanotechnology-based techniques for detecting lung cancer through EV analysis. It begins by providing a brief overview of exosomes and their role in lung cancer progression. Furthermore, this review explores the evolving landscape of EV isolation and cargo analysis, highlighting the importance of characterizing specific biomolecular signatures within EVs for improved diagnostic accuracy in lung cancer patients. Innovative strategies for enhancing the sensitivity and specificity of EV isolation and detection, including the integration of microfluidic platforms and multiplexed biosensing technologies are summarized. The discussion then extends to key challenges associated with EV-based liquid biopsies, such as the standardization of isolation and detection protocols and the establishment of robust analytical platforms for clinical translation. This review highlights the transformative impact of EV-based liquid biopsy in lung cancer diagnosis, heralding a new era of personalized medicine and improved patient care.
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Affiliation(s)
- Sunil Vasu
- Department of Chemical Engineering, Indian Institute of Technology Tirupati, Tirupati, Andhra Pradesh, India-517 619
| | - Vinith Johnson
- Department of Chemical Engineering, Indian Institute of Technology Tirupati, Tirupati, Andhra Pradesh, India-517 619
| | - Archana M
- Department of Chemical Engineering, Indian Institute of Technology Tirupati, Tirupati, Andhra Pradesh, India-517 619
| | - K Anki Reddy
- Department of Chemical Engineering, Indian Institute of Technology Tirupati, Tirupati, Andhra Pradesh, India-517 619
| | - Uday Kumar Sukumar
- Department of Chemical Engineering, Indian Institute of Technology Tirupati, Tirupati, Andhra Pradesh, India-517 619
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Rodríguez-Sanz J, Muñoz-González N, Cubero JP, Ordoñez P, Gil V, Langarita R, Ruiz M, Forner M, Marín-Oto M, Vera E, Baptista P, Polverino F, Domingo JA, García-Tirado J, Marin JM, Sanz-Rubio D. Peripheral Extracellular Vesicles for Diagnosis and Prognosis of Resectable Lung Cancer: The LUCEx Study Protocol. J Clin Med 2025; 14:411. [PMID: 39860417 PMCID: PMC11765880 DOI: 10.3390/jcm14020411] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2024] [Revised: 12/27/2024] [Accepted: 01/07/2025] [Indexed: 01/27/2025] Open
Abstract
Background/Objectives: Lung cancer is the primary cause of cancer-related deaths. Most patients are typically diagnosed at advanced stages. Low-dose computed tomography (LDCT) has been proven to reduce lung cancer mortality, but screening programs using LDCT are associated with a high number of false positives and unnecessary thoracotomies. It is therefore imperative that a certain diagnosis is refined, especially in cases of solitary pulmonary nodules that are difficult to technically access for an accurate preoperative diagnosis. Extracellular vesicles (EVs) involved in intercellular communication may be an innovative biomarker for diagnosis and therapeutic strategies in lung cancer, regarding their ability to carry tumor-specific cargo. The aim of the LUCEx study is to determine if extracellular vesicle cargoes from both lung tissue and blood could provide complementary information to screen lung cancer patients and enable personalized follow-up after the surgery. Methods: The LUCEx study is a prospective study aiming to recruit 600 patients with lung cancer and 50 control subjects (false positives) undergoing surgery after diagnostic imaging for suspected pulmonary nodules using computed tomography (CT) scans. These patients will undergo curative surgery at the Department of Thoracic Surgery of the Miguel Servet Hospital in Zaragoza, Spain, and will be followed-up for at least 5 years. At baseline, samples from both tumor distal lung tissue and preoperative peripheral blood will be collected and processed to compare the quantity and content of EVs, particularly their micro-RNA (miRNA) cargo. At the third and fifth years of follow-up, CT scans, functional respiratory tests, and blood extractions will be performed. Discussion: Extracellular vesicles and their miRNA have emerged as promising tools for the diagnosis and prognosis of several diseases, including cancer. The LUCEx study, based on an observational clinical cohort, aims to understand the role of these vesicles and their translational potential as complementary tools for imaging diagnosis and prognosis.
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Affiliation(s)
- Jorge Rodríguez-Sanz
- Pulmonology and Critical Care Unit, Hospital Universitario Miguel Servet, 50009 Zaragoza, Spain
- Translational Research Unit, Hospital Universitario Miguel Servet, IIS Aragón, 50009 Zaragoza, Spain
- CIBER Enfermedades Respiratorias, 28029 Madrid, Spain
| | - Nadia Muñoz-González
- Translational Research Unit, Hospital Universitario Miguel Servet, IIS Aragón, 50009 Zaragoza, Spain
- CIBER Enfermedades Respiratorias, 28029 Madrid, Spain
- Thoracic Surgery Unit, Hospital Universitario Miguel Servet, 50009 Zaragoza, Spain
| | - José Pablo Cubero
- Translational Research Unit, Hospital Universitario Miguel Servet, IIS Aragón, 50009 Zaragoza, Spain
- CIBER Enfermedades Respiratorias, 28029 Madrid, Spain
| | - Pablo Ordoñez
- Thoracic Surgery Unit, Hospital Universitario Miguel Servet, 50009 Zaragoza, Spain
| | - Victoria Gil
- Translational Research Unit, Hospital Universitario Miguel Servet, IIS Aragón, 50009 Zaragoza, Spain
- CIBER Enfermedades Respiratorias, 28029 Madrid, Spain
| | - Raquel Langarita
- Translational Research Unit, Hospital Universitario Miguel Servet, IIS Aragón, 50009 Zaragoza, Spain
- CIBER Enfermedades Respiratorias, 28029 Madrid, Spain
| | - Myriam Ruiz
- Translational Research Unit, Hospital Universitario Miguel Servet, IIS Aragón, 50009 Zaragoza, Spain
- CIBER Enfermedades Respiratorias, 28029 Madrid, Spain
| | - Marta Forner
- Translational Research Unit, Hospital Universitario Miguel Servet, IIS Aragón, 50009 Zaragoza, Spain
- CIBER Enfermedades Respiratorias, 28029 Madrid, Spain
| | - Marta Marín-Oto
- Translational Research Unit, Hospital Universitario Miguel Servet, IIS Aragón, 50009 Zaragoza, Spain
- CIBER Enfermedades Respiratorias, 28029 Madrid, Spain
| | - Elisabet Vera
- Pulmonology and Critical Care Unit, Hospital Universitario Miguel Servet, 50009 Zaragoza, Spain
| | - Pedro Baptista
- Instituto de Investigación Sanitaria de Aragón (IIS Aragón), 50009 Zaragoza, Spain
| | - Francesca Polverino
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Baylor College of Medicine, Houston, TX 77030, USA
| | - Juan Antonio Domingo
- Pulmonology and Critical Care Unit, Hospital Universitario Miguel Servet, 50009 Zaragoza, Spain
| | - Javier García-Tirado
- Thoracic Surgery Unit, Hospital Universitario Miguel Servet, 50009 Zaragoza, Spain
| | - José María Marin
- Pulmonology and Critical Care Unit, Hospital Universitario Miguel Servet, 50009 Zaragoza, Spain
- Translational Research Unit, Hospital Universitario Miguel Servet, IIS Aragón, 50009 Zaragoza, Spain
- CIBER Enfermedades Respiratorias, 28029 Madrid, Spain
| | - David Sanz-Rubio
- Translational Research Unit, Hospital Universitario Miguel Servet, IIS Aragón, 50009 Zaragoza, Spain
- CIBER Enfermedades Respiratorias, 28029 Madrid, Spain
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Doghish AS, Abulsoud AI, Nassar YA, Nasr SM, Mohammed OA, Abdel-Reheim MA, Rizk NI, Lutfy RH, Abdel Mageed SS, Ismail MA, Abd-Elhalim HM, Awad FA, Fayez SZ, Elimam H, Mansour RM. Harnessing miRNAs: A Novel Approach to Diagnosis and Treatment of Tuberculosis. J Biochem Mol Toxicol 2025; 39:e70119. [PMID: 39799557 DOI: 10.1002/jbt.70119] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Revised: 12/09/2024] [Accepted: 12/21/2024] [Indexed: 01/15/2025]
Abstract
Mycobacterium tuberculosis (Mtb) complex, responsible for tuberculosis (TB) infection, continues to be a predominant global cause of mortality due to intricate host-pathogen interactions that affect disease progression. MicroRNAs (miRNAs), essential posttranscriptional regulators, have become pivotal modulators of these relationships. Recent findings indicate that miRNAs actively regulate immunological responses to Mtb complex by modulating autophagy, apoptosis, and immune cell activities. This has resulted in increased interest in miRNAs as prospective diagnostic indicators for TB, especially in differentiating active infection from latent or inactive stages. Variations in miRNA expression during Mtb infection indicate disease progression and offer insights into the immune response. Furthermore, miRNAs present potential as therapeutic targets in host-directed therapy (HDT) techniques for TB infection. This work examines the function of miRNAs in TB pathogenesis, with the objective of identifying particular miRNAs that regulate the immune response to the Mtb complex, evaluating their diagnostic value and exploring their therapeutic implications in host-directed therapy for TB infection. The objective is to enhance comprehension of how miRNAs can facilitate improved diagnosis and treatment of TB.
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Affiliation(s)
- Ahmed S Doghish
- Department of Biochemistry, Badr University in Cairo (BUC), Badr City, Cairo, Egypt
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, Cairo, Egypt
| | - Ahmed I Abulsoud
- Biochemistry Department, Faculty of Pharmacy, Heliopolis University, Cairo, Egypt
| | - Yara A Nassar
- Department of Botany, Biotechnology and Its Application Program, Faculty of Science, Mansoura University, Mansoura, Egypt
| | - Sami Mohamed Nasr
- Biochemistry and Molecular Biology, Theodor Bilharz Research Institute, Giza, Egypt
- School of Biotechnology, Badr University in Cairo, Badr City, Cairo, Egypt
| | - Osama A Mohammed
- Department of Pharmacology, College of Medicine, University of Bisha, Bisha, Saudi Arabia
| | | | - Nehal I Rizk
- Department of Biochemistry, Faculty of Pharmacy and Drug Technology, Egyptian Chinese University, Cairo, Egypt
| | - Radwa H Lutfy
- School of Biotechnology, Badr University in Cairo, Badr City, Cairo, Egypt
| | - Sherif S Abdel Mageed
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo, Egypt
| | - Menattallah A Ismail
- Applied Biotechnology Program, Faculty of Science, Ain Shams University, Cairo, Egypt
| | - Haytham M Abd-Elhalim
- School of Biotechnology, Badr University in Cairo, Badr City, Cairo, Egypt
- Agricultural Research Center, Agricultural Genetic Engineering Research Institute, Giza, Egypt
| | - Farah A Awad
- School of Biotechnology, Badr University in Cairo, Badr City, Cairo, Egypt
| | - Salma Zaki Fayez
- School of Biotechnology, Badr University in Cairo, Badr City, Cairo, Egypt
| | - Hanan Elimam
- Department of Biochemistry, Faculty of Pharmacy, University of Sadat City, Sadat City, Egypt
| | - Reda M Mansour
- Zoology and Entomology Department, Faculty of Science, Helwan University, Helwan, Egypt
- Molecular Biology and Biotechnology Department, School of Biotechnology, Badr University in Cairo (BUC), Badr City, Cairo, Egypt
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7
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Kang HJ, Yun S, Shin SH, Youn DH, Son GH, Lee JJ, Hong JY. Tuberculous Pleural Effusion-Derived Exosomal miR-130b-3p and miR-423-5p Promote the Proliferation of Lung Cancer Cells via Cyclin D1. Int J Mol Sci 2024; 25:10119. [PMID: 39337604 PMCID: PMC11431986 DOI: 10.3390/ijms251810119] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2024] [Revised: 09/08/2024] [Accepted: 09/16/2024] [Indexed: 09/30/2024] Open
Abstract
Epidemiologic studies have shown an association between tuberculosis and lung cancer. The altered tumor microenvironment after tuberculosis infection appears to contribute to cancer progression. Pleural effusions are enriched in exosomes, which act as mediators of intercellular communication. We hypothesized that tuberculous pleural effusion (TPE)-derived exosomes mediate intercellular communication. Then, we examined the interaction between TPE-derived exosomes and cancer cells. Exosomal miRNA profiling of TPE was performed using a microRNA array. An in vitro lung cancer cell experiment and an in vivo mouse xenograft tumor model were used to evaluate the effects of the selected exosomal microRNAs. TPE-derived exosome treatment enhanced the growth of A549 cells both in vitro and in a nude mouse xenograft model. Neighboring cancer cells were observed to take up TPE-derived exosomes, which promoted cancer cell invasion. Exosome-mediated transfer of the selected microRNAs, including miR-130b-3p and miR-423-5p, to A549 lung cancer cells activated cyclin D1 signaling and increased the expression of phosphorylated p65, a cyclin D1 transcription factor. Inhibitors of miR-130b and miR-423-5p suppressed the promotion of lung cancer by TPE-derived exosomes and reduced the expression of p65 and cyclin D1. These results suggest that TPE-derived exosomal miRNAs can serve as a novel therapeutic target in tuberculous fibrosis-induced lung cancer.
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Affiliation(s)
- Hyun-Jung Kang
- Institute of New Frontier Research Team, Hallym University College of Medicine, Chuncheon 24252, Republic of Korea; (H.-J.K.); (S.Y.); (S.-H.S.); (D.H.Y.); (G.-H.S.)
| | - Sangho Yun
- Institute of New Frontier Research Team, Hallym University College of Medicine, Chuncheon 24252, Republic of Korea; (H.-J.K.); (S.Y.); (S.-H.S.); (D.H.Y.); (G.-H.S.)
| | - Seung-Ho Shin
- Institute of New Frontier Research Team, Hallym University College of Medicine, Chuncheon 24252, Republic of Korea; (H.-J.K.); (S.Y.); (S.-H.S.); (D.H.Y.); (G.-H.S.)
| | - Dong Hyuk Youn
- Institute of New Frontier Research Team, Hallym University College of Medicine, Chuncheon 24252, Republic of Korea; (H.-J.K.); (S.Y.); (S.-H.S.); (D.H.Y.); (G.-H.S.)
| | - Ga-Hyun Son
- Institute of New Frontier Research Team, Hallym University College of Medicine, Chuncheon 24252, Republic of Korea; (H.-J.K.); (S.Y.); (S.-H.S.); (D.H.Y.); (G.-H.S.)
| | - Jae Jun Lee
- Institute of New Frontier Research Team, Hallym University College of Medicine, Chuncheon 24252, Republic of Korea; (H.-J.K.); (S.Y.); (S.-H.S.); (D.H.Y.); (G.-H.S.)
| | - Ji Young Hong
- Institute of New Frontier Research Team, Hallym University College of Medicine, Chuncheon 24252, Republic of Korea; (H.-J.K.); (S.Y.); (S.-H.S.); (D.H.Y.); (G.-H.S.)
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Chuncheon Sacred Heart Hospital, Hallym University Medical Center, Chuncheon 24252, Republic of Korea
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Wu J, Chen Y. Unraveling the Connection: Extracellular Vesicles and Non-Small Cell Lung Cancer. Int J Nanomedicine 2024; 19:8139-8157. [PMID: 39139506 PMCID: PMC11321355 DOI: 10.2147/ijn.s477851] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2024] [Accepted: 08/04/2024] [Indexed: 08/15/2024] Open
Abstract
Extracellular vesicles (EVs) are nanoscale lipid bilayer vesicles released during cell activation, cellular damage, or apoptosis. They carry nucleic acids, proteins, and lipids facilitating intercellular communication and activate signaling pathways in target cells. In non-small cell lung cancer (NSCLC), EVs may contribute to tumor growth and metastasis by modulating immune responses, facilitating epithelial-mesenchymal transition, and promoting angiogenesis, while potentially contributing to resistance to chemotherapy drugs. EVs in liquid biopsies serve as non-invasive biomarkers for early cancer detection and diagnosis. Due to their small size, inherent molecular transport properties, and excellent biocompatibility, EVs also act as natural drug delivery vehicles in NSCLC therapy.
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Affiliation(s)
- Jiankang Wu
- Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China
- Research Unit of Respiratory Disease, Central South University, Changsha, Hunan, People’s Republic of China
- Clinical Medical Research Center for Pulmonary and Critical Care Medicine, Changsha, Hunan, People’s Republic of China
- Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, Hunan, People’s Republic of China
| | - Yan Chen
- Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China
- Research Unit of Respiratory Disease, Central South University, Changsha, Hunan, People’s Republic of China
- Clinical Medical Research Center for Pulmonary and Critical Care Medicine, Changsha, Hunan, People’s Republic of China
- Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, Hunan, People’s Republic of China
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Rahimian S, Najafi H, Afzali B, Doroudian M. Extracellular Vesicles and Exosomes: Novel Insights and Perspectives on Lung Cancer from Early Detection to Targeted Treatment. Biomedicines 2024; 12:123. [PMID: 38255228 PMCID: PMC10813125 DOI: 10.3390/biomedicines12010123] [Citation(s) in RCA: 11] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Revised: 12/24/2023] [Accepted: 01/04/2024] [Indexed: 01/24/2024] Open
Abstract
Lung cancer demands innovative approaches for early detection and targeted treatment. In addressing this urgent need, exosomes play a pivotal role in revolutionizing both the early detection and targeted treatment of lung cancer. Their remarkable capacity to encapsulate a diverse range of biomolecules, traverse biological barriers, and be engineered with specific targeting molecules makes them highly promising for both diagnostic markers and precise drug delivery to cancer cells. Furthermore, an in-depth analysis of exosomal content and biogenesis offers crucial insights into the molecular profile of lung tumors. This knowledge holds significant potential for the development of targeted therapies and innovative diagnostic strategies for cancer. Despite notable progress in this field, challenges in standardization and cargo loading persist. Collaborative research efforts are imperative to maximize the potential of exosomes and advance the field of precision medicine for the benefit of lung cancer patients.
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Affiliation(s)
| | | | | | - Mohammad Doroudian
- Department of Cell and Molecular Sciences, Faculty of Biological Sciences, Kharazmi University, Tehran 14911-15719, Iran; (S.R.); (H.N.); (B.A.)
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10
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Khan NA, Asim M, Biswas KH, Alansari AN, Saman H, Sarwar MZ, Osmonaliev K, Uddin S. Exosome nanovesicles as potential biomarkers and immune checkpoint signaling modulators in lung cancer microenvironment: recent advances and emerging concepts. J Exp Clin Cancer Res 2023; 42:221. [PMID: 37641132 PMCID: PMC10463467 DOI: 10.1186/s13046-023-02753-7] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2023] [Accepted: 07/08/2023] [Indexed: 08/31/2023] Open
Abstract
Lung cancer remains the leading cause of cancer-related deaths globally, and the survival rate remains low despite advances in diagnosis and treatment. The progression of lung cancer is a multifaceted and dynamic phenomenon that encompasses interplays among cancerous cells and their microenvironment, which incorporates immune cells. Exosomes, which are small membrane-bound vesicles, are released by numerous cell types in normal and stressful situations to allow communication between cells. Tumor-derived exosomes (TEXs) possess diverse neo-antigens and cargoes such as proteins, RNA, and DNA and have a unique molecular makeup reflecting tumor genetic complexity. TEXs contain both immunosuppressive and immunostimulatory factors and may play a role in immunomodulation by influencing innate and adaptive immune components. Moreover, they transmit signals that contribute to the progression of lung cancer by promoting metastasis, epithelial-mesenchymal transition (EMT), angiogenesis, and immunosuppression. This makes them a valuable resource for investigating the immune environment of tumors, which could pave the way for the development of non-invasive biomarkers that could aid in the prognosis, diagnosis, and immunotherapy of lung cancer. While immune checkpoint inhibitor (ICI) immunotherapy has shown promising results in treating initial-stage cancers, most patients eventually develop adaptive resistance over time. Emerging evidence demonstrates that TEXs could serve as a prognostic biomarker for immunotherapeutic response and have a significant impact on both systemic immune suppression and tumor advancement. Therefore, understanding TEXs and their role in lung cancer tumorigenesis and their response to immunotherapies is an exciting research area and needs further investigation. This review highlights the role of TEXs as key contributors to the advancement of lung cancer and their clinical significance in lung immune-oncology, including their possible use as biomarkers for monitoring disease progression and prognosis, as well as emerging shreds of evidence regarding the possibility of using exosomes as targets to improve lung cancer therapy.
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Affiliation(s)
- Naushad Ahmad Khan
- Department of Surgery, Trauma and Vascular Surgery Clinical Research, Hamad General Hospital, 3050, Doha, Qatar.
- Faculty of Medical Sciences, Ala-Too International University, Bishkek, Kyrgyzstan.
| | - Mohammad Asim
- Department of Surgery, Trauma and Vascular Surgery Clinical Research, Hamad General Hospital, 3050, Doha, Qatar
| | - Kabir H Biswas
- Division of Biological and Biomedical Sciences, College of Health & Life Sciences, Hamad Bin Khalifa University, Qatar Foundation, Doha, Qatar
| | - Amani N Alansari
- Department of Surgery, Trauma and Vascular Surgery Clinical Research, Hamad General Hospital, 3050, Doha, Qatar
| | - Harman Saman
- Department of Medicine, Hazm Maubrairek Hospital, Al-Rayyan, Doha, 3050, Qatar
| | | | | | - Shahab Uddin
- Translational Research Institute & Dermatology Institute, Academic Health System, Hamad Medical Corporation, Doha, 3050, Qatar.
- Department of Biosciences, Integral University, Lucknow, 226026, UP, India.
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11
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Yang Q, Luo J, Xu H, Huang L, Zhu X, Li H, Yang R, Peng B, Sun D, Zhu Q, Liu F. Metabolomic investigation of urinary extracellular vesicles for early detection and screening of lung cancer. J Nanobiotechnology 2023; 21:153. [PMID: 37189121 DOI: 10.1186/s12951-023-01908-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Accepted: 04/24/2023] [Indexed: 05/17/2023] Open
Abstract
Lung cancer is a prevalent cancer type worldwide that often remains asymptomatic in its early stages and is frequently diagnosed at an advanced stage with a poor prognosis due to the lack of effective diagnostic techniques and molecular biomarkers. However, emerging evidence suggests that extracellular vesicles (EVs) may promote lung cancer cell proliferation and metastasis, and modulate the anti-tumor immune response in lung cancer carcinogenesis, making them potential biomarkers for early cancer detection. To investigate the potential of urinary EVs for non-invasive detection and screening of patients at early stages, we studied metabolomic signatures of lung cancer. Specifically, we conducted metabolomic analysis of 102 EV samples and identified metabolome profiles of urinary EVs, including organic acids and derivatives, lipids and lipid-like molecules, organheterocyclic compounds, and benzenoids. Using machine learning with a random forest model, we screened for potential markers of lung cancer and identified a marker panel consisting of Kanzonol Z, Xanthosine, Nervonyl carnitine, and 3,4-Dihydroxybenzaldehyde, which exhibited a diagnostic potency of 96% for the testing cohort (AUC value). Importantly, this marker panel also demonstrated effective prediction for the validation set, with an AUC value of 84%, indicating the reliability of the marker screening process. Our findings suggest that the metabolomic analysis of urinary EVs provides a promising source of non-invasive markers for lung cancer diagnostics. We believe that the EV metabolic signatures could be used to develop clinical applications for the early detection and screening of lung cancer, potentially improving patient outcomes.
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Affiliation(s)
- Qinsi Yang
- Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang, 325000, China
| | - Jiaxin Luo
- National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China
| | - Hao Xu
- National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China
| | - Liu Huang
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
| | - Xinxi Zhu
- Key Laboratory of Heart and Lung, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China
| | - Hengrui Li
- National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China
| | - Rui Yang
- National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China
| | - Bo Peng
- Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang, 325000, China
| | - Da Sun
- Institute of Life Sciences & Engineering Laboratory of Zhejiang Province for Pharmaceutical Development of Growth Factors, Wenzhou University, Wenzhou, 325035, China
| | - Qingfu Zhu
- National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China.
| | - Fei Liu
- The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.
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12
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Zhang X, Bao L, Yu G, Wang H. Exosomal miRNA-profiling of pleural effusion in lung adenocarcinoma and tuberculosis. Front Surg 2023; 9:1050242. [PMID: 36684253 PMCID: PMC9852630 DOI: 10.3389/fsurg.2022.1050242] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Accepted: 11/21/2022] [Indexed: 01/09/2023] Open
Abstract
Background Pleural effusion (PE) caused by lung cancer is prevalent, and it is difficult to differentiate it from PE caused by tuberculosis. Exosome-based liquid biopsy offers a non-invasive technique to diagnose benign and malignant PE. Exosomal miRNAs are potential diagnostic markers and play an essential role in signal transduction and biological processes in tumor development. We hypothesized that exosomal miRNA expression profiles in PE would contribute to identifying its diagnostic markers and elucidating the molecular basis of PE formation in lung cancer. Methods The exosomes from PE caused by lung adenocarcinoma (LUAD) and pulmonary tuberculosis were isolated and verified by transmission electron microscopy. The exosomal miRNA profiles were identified using deep sequencing and validated with quantitative real-time PCR (qRT-PCR). We performed bioinformatic analysis for differentially expressed miRNAs to explore how exosomal miRNAs regulate pleural effusion. Results We identified 99 upregulated and 91 downregulated miRNAs in malignant pleural effusion (MPE) compared to tuberculous pleural effusion (TPE). Seven differentially expressed miRNAs (DEmiRNAs) were validated by qRT-PCR, out of which 5 (71.4%) were confirmed through sequencing. Gene Ontology (GO) analysis revealed that most exosomal miRNAs target genes were involved in regulating cellular processes and nitrogen compound metabolism. According to the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, the exosomal miRNAs target genes were mainly involved in Fc gamma R-mediated phagocytosis, Rap1 signaling pathway, and breast cancer. The hub genes, including ITGAM, FOXO1, MAPK14, YWHAB, GRIN1, and PRF1, were screened through plug-in cytoHubba. The PFR1 was identified as a critical gene in MPE formation using single-cell sequencing analysis. Additionally, we hypothesized that tumor cells affected natural killer cells and promoted the generation of PE in LUAD via the exosomal hsa-miR-3120-5p-PRF1 axis. Conclusions We identified exosomal miRNA profiles in LUAD-MPE and TPE, which may help in the differential diagnosis of MPE and TPE. Bioinformatic analysis revealed that these miRNAs might affect PE generation through tumor immune response in LUAD. Our results provided a new theoretical basis for understanding the function of exosomal miRNAs in LUAD-MPE.
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Affiliation(s)
- Xuede Zhang
- Department of Oncology, Weifang People's Hospital, Weifang, China
| | - Lingling Bao
- Department of Hematology and Oncology, Beilun District People's Hospital, Ningbo, China
| | - Guohua Yu
- Department of Oncology, Weifang People's Hospital, Weifang, China
| | - Haifeng Wang
- Department of Hematology and Oncology, Beilun District People's Hospital, Ningbo, China,Correspondence: Haifeng Wang
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Jafari A, Karimabadi K, Rahimi A, Rostaminasab G, Khazaei M, Rezakhani L, Ahmadi jouybari T. The Emerging Role of Exosomal miRNAs as Biomarkers for Early Cancer Detection: A Comprehensive Literature Review. Technol Cancer Res Treat 2023; 22:15330338231205999. [PMID: 37817634 PMCID: PMC10566290 DOI: 10.1177/15330338231205999] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2023] [Revised: 09/10/2023] [Accepted: 09/13/2023] [Indexed: 10/12/2023] Open
Abstract
A significant number of cancer-related deaths are recorded globally each year, despite attempts to cure this illness. Medical science is working to develop new medication therapies as well as to find ways to identify this illness as early as possible, even using noninvasive techniques. Early detection of cancer can greatly aid its treatment. Studies into cancer diagnosis and therapy have recently shifted their focus to exosome (EXO) biomarkers, which comprise numerous RNA and proteins. EXOs are minuscule goblet vesicles that have a width of 30 to 140 nm and are released by a variety of cells, including immune, stem, and tumor cells, as well as bodily fluids. According to a growing body of research, EXOs, and cancer appear to be related. EXOs from tumors play a role in the genetic information transfer between tumor and basal cells, which controls angiogenesis and fosters tumor development and spread. To identify malignant activities early on, microRNAs (miRNAs) from cancers can be extracted from circulatory system EXOs. Specific markers can be used to identify cancer-derived EXOs containing miRNAs, which may be more reliable and precise for early detection. Conventional solid biopsy has become increasingly limited as precision and personalized medicine has advanced, while liquid biopsy offers a viable platform for noninvasive diagnosis and prognosis. Therefore, the use of body fluids such as serum, plasma, urine, and salivary secretions can help find cancer biomarkers using technologies related to EXOs.
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Affiliation(s)
- Ali Jafari
- Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Keyvan Karimabadi
- Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Aso Rahimi
- Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Gelavizh Rostaminasab
- Clinical Research Development Center, Imam Khomeini and Mohammad Kermanshahi and Farabi Hospitals, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Mozafar Khazaei
- Fertility and Infertility Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
- Department of Tissue Engineering, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Leila Rezakhani
- Fertility and Infertility Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
- Department of Tissue Engineering, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Touraj Ahmadi jouybari
- Clinical Research Development Center, Imam Khomeini and Mohammad Kermanshahi and Farabi Hospitals, Kermanshah University of Medical Sciences, Kermanshah, Iran
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14
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Zhao W, Cao XS, Han YL, Wen XH, Zheng WQ, Hu ZD. Diagnostic utility of pleural cell-free nucleic acids in undiagnosed pleural effusions. Clin Chem Lab Med 2022; 60:1518-1524. [PMID: 35786439 DOI: 10.1515/cclm-2022-0519] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Accepted: 06/22/2022] [Indexed: 11/15/2022]
Abstract
Pleural effusion (PE) is a common sign caused by various disorders. Microbiology, histology and cytology are reference standards for these disorders. However, these diagnostic tools have limitations, including invasiveness, high cost, long turnaround time, and observer-dependent. Soluble biomarkers in pleural fluid (PF) are promising diagnostic tools because they are mininvasive, economical, and objective. Recent studies have revealed that some cell-free nucleic acids (e.g., DNA, mRNA, microRNA, and lncRNA) in PF are potential diagnostic markers for many disorders. Here, we review the performance of PF cell-free nucleic acids for differentiating and stratification of PE.
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Affiliation(s)
- Wen Zhao
- Department of Laboratory Medicine, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, P.R. China
| | - Xi-Shan Cao
- Department of Laboratory Medicine, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, P.R. China
| | - Yu-Ling Han
- Department of Laboratory Medicine, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, P.R. China
| | - Xu-Hui Wen
- Department of Laboratory Medicine, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, P.R. China
| | - Wen-Qi Zheng
- Department of Laboratory Medicine, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, P.R. China
| | - Zhi-De Hu
- Department of Laboratory Medicine, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, P.R. China
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15
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Han B, Molins L, He Y, Viñolas N, Sánchez-Lorente D, Boada M, Guirao A, Díaz T, Martinez D, Ramirez J, Moisés J, Acosta-Plasencia M, Monzo M, Marrades RM, Navarro A. Characterization of the MicroRNA Cargo of Extracellular Vesicles Isolated from a Pulmonary Tumor-Draining Vein Identifies miR-203a-3p as a Relapse Biomarker for Resected Non-Small Cell Lung Cancer. Int J Mol Sci 2022; 23:ijms23137138. [PMID: 35806142 PMCID: PMC9266391 DOI: 10.3390/ijms23137138] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Revised: 06/21/2022] [Accepted: 06/23/2022] [Indexed: 02/05/2023] Open
Abstract
In resected non-small cell lung cancer (NSCLC), post-surgical recurrence occurs in around 40% of patients, highlighting the necessity to identify relapse biomarkers. An analysis of the extracellular vesicle (EV) cargo from a pulmonary tumor-draining vein (TDV) can grant biomarker identification. We studied the pulmonary TDV EV-miRNAome to identify relapse biomarkers in a two-phase study (screening and validation). In the screening phase, a 17-miRNA relapse signature was identified in 18 selected patients by small RNAseq. The most expressed miRNA from the signature (EV-miR-203a-3p) was chosen for further validation. Pulmonary TDV EV-miR-203a-3p was studied by qRT-PCR in a validation cohort of 70 patients, where it was found to be upregulated in relapsed patients (p = 0.0194) and in patients with cancer spread to nearby lymph nodes (N+ patients) (p = 0.0396). The ROC curve analysis showed that TDV EV-miR-203a-3p was able to predict relapses with a sensitivity of 88% (AUC: 0.67; p = 0.022). Moreover, patients with high TDV EV-miR-203a-3p had a shorter time to relapse than patients with low levels (43.6 vs. 97.6 months; p = 0.00703). The multivariate analysis showed that EV-miR-203a-3p was an independent, predictive and prognostic post-surgical relapse biomarker. In conclusion, pulmonary TDV EV-miR-203a-3p is a promising new relapse biomarker for resected NSCLC patients.
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Affiliation(s)
- Bing Han
- Molecular Oncology and Embryology Laboratory, Department of Surgery and Medical Specializations, Human Anatomy Unit, Faculty of Medicine and Health Sciences, Universitat de Barcelona (UB), c. Casanova 143, 08036 Barcelona, Spain; (B.H.); (Y.H.); (T.D.); (M.A.-P.); (M.M.)
| | - Laureano Molins
- Department of Thoracic Surgery, Hospital Clínic de Barcelona, University of Barcelona, 08036 Barcelona, Spain; (L.M.); (D.S.-L.); (M.B.); (A.G.)
- Thoracic Oncology Unit, Hospital Clinic, 08036 Barcelona, Spain; (N.V.); (D.M.); (J.R.); (R.M.M.)
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), c. Villarroel, 170, 08036 Barcelona, Spain;
| | - Yangyi He
- Molecular Oncology and Embryology Laboratory, Department of Surgery and Medical Specializations, Human Anatomy Unit, Faculty of Medicine and Health Sciences, Universitat de Barcelona (UB), c. Casanova 143, 08036 Barcelona, Spain; (B.H.); (Y.H.); (T.D.); (M.A.-P.); (M.M.)
- School of Basic Medical Sciences, Chengdu University, Chengdu 610106, China
| | - Nuria Viñolas
- Thoracic Oncology Unit, Hospital Clinic, 08036 Barcelona, Spain; (N.V.); (D.M.); (J.R.); (R.M.M.)
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), c. Villarroel, 170, 08036 Barcelona, Spain;
- Department of Medical Oncology, Institut Clínic de Malalties Hemato-Oncològiques (ICMHO), Hospital Clínic de Barcelona, University of Barcelona, 08036 Barcelona, Spain
| | - David Sánchez-Lorente
- Department of Thoracic Surgery, Hospital Clínic de Barcelona, University of Barcelona, 08036 Barcelona, Spain; (L.M.); (D.S.-L.); (M.B.); (A.G.)
- Thoracic Oncology Unit, Hospital Clinic, 08036 Barcelona, Spain; (N.V.); (D.M.); (J.R.); (R.M.M.)
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), c. Villarroel, 170, 08036 Barcelona, Spain;
| | - Marc Boada
- Department of Thoracic Surgery, Hospital Clínic de Barcelona, University of Barcelona, 08036 Barcelona, Spain; (L.M.); (D.S.-L.); (M.B.); (A.G.)
- Thoracic Oncology Unit, Hospital Clinic, 08036 Barcelona, Spain; (N.V.); (D.M.); (J.R.); (R.M.M.)
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), c. Villarroel, 170, 08036 Barcelona, Spain;
| | - Angela Guirao
- Department of Thoracic Surgery, Hospital Clínic de Barcelona, University of Barcelona, 08036 Barcelona, Spain; (L.M.); (D.S.-L.); (M.B.); (A.G.)
- Thoracic Oncology Unit, Hospital Clinic, 08036 Barcelona, Spain; (N.V.); (D.M.); (J.R.); (R.M.M.)
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), c. Villarroel, 170, 08036 Barcelona, Spain;
| | - Tania Díaz
- Molecular Oncology and Embryology Laboratory, Department of Surgery and Medical Specializations, Human Anatomy Unit, Faculty of Medicine and Health Sciences, Universitat de Barcelona (UB), c. Casanova 143, 08036 Barcelona, Spain; (B.H.); (Y.H.); (T.D.); (M.A.-P.); (M.M.)
| | - Daniel Martinez
- Thoracic Oncology Unit, Hospital Clinic, 08036 Barcelona, Spain; (N.V.); (D.M.); (J.R.); (R.M.M.)
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), c. Villarroel, 170, 08036 Barcelona, Spain;
- Department of Pathology, Hospital Clínic de Barcelona, University of Barcelona, 08036 Barcelona, Spain
| | - Jose Ramirez
- Thoracic Oncology Unit, Hospital Clinic, 08036 Barcelona, Spain; (N.V.); (D.M.); (J.R.); (R.M.M.)
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), c. Villarroel, 170, 08036 Barcelona, Spain;
- Department of Pathology, Hospital Clínic de Barcelona, University of Barcelona, 08036 Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Jorge Moisés
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), c. Villarroel, 170, 08036 Barcelona, Spain;
- Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Melissa Acosta-Plasencia
- Molecular Oncology and Embryology Laboratory, Department of Surgery and Medical Specializations, Human Anatomy Unit, Faculty of Medicine and Health Sciences, Universitat de Barcelona (UB), c. Casanova 143, 08036 Barcelona, Spain; (B.H.); (Y.H.); (T.D.); (M.A.-P.); (M.M.)
| | - Mariano Monzo
- Molecular Oncology and Embryology Laboratory, Department of Surgery and Medical Specializations, Human Anatomy Unit, Faculty of Medicine and Health Sciences, Universitat de Barcelona (UB), c. Casanova 143, 08036 Barcelona, Spain; (B.H.); (Y.H.); (T.D.); (M.A.-P.); (M.M.)
- Thoracic Oncology Unit, Hospital Clinic, 08036 Barcelona, Spain; (N.V.); (D.M.); (J.R.); (R.M.M.)
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), c. Villarroel, 170, 08036 Barcelona, Spain;
| | - Ramón M. Marrades
- Thoracic Oncology Unit, Hospital Clinic, 08036 Barcelona, Spain; (N.V.); (D.M.); (J.R.); (R.M.M.)
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), c. Villarroel, 170, 08036 Barcelona, Spain;
- Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, 28029 Madrid, Spain
- Department of Pneumology, Institut Clínic Respiratori (ICR), Hospital Clínic de Barcelona, University of Barcelona, 08036 Barcelona, Spain
| | - Alfons Navarro
- Molecular Oncology and Embryology Laboratory, Department of Surgery and Medical Specializations, Human Anatomy Unit, Faculty of Medicine and Health Sciences, Universitat de Barcelona (UB), c. Casanova 143, 08036 Barcelona, Spain; (B.H.); (Y.H.); (T.D.); (M.A.-P.); (M.M.)
- Thoracic Oncology Unit, Hospital Clinic, 08036 Barcelona, Spain; (N.V.); (D.M.); (J.R.); (R.M.M.)
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), c. Villarroel, 170, 08036 Barcelona, Spain;
- Correspondence: ; Tel.: +34-93-4021903
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Soni A, Guliani A, Nehra K, Mehta PK. Insight into diagnosis of pleural tuberculosis with special focus on nucleic acid amplification tests. Expert Rev Respir Med 2022; 16:887-906. [PMID: 35728039 DOI: 10.1080/17476348.2022.2093189] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
INTRODUCTION Pleural tuberculosis (TB) is the archetype of extrapulmonary TB (EPTB), which mainly affects the pleural space and leads to exudative pleural effusion. Diagnosis of pleural TB is a difficult task predominantly due to atypical clinical presentations and sparse bacillary load in clinical specimens. AREA COVERED We reviewed the current literature on the globally existing conventional/latest modalities for diagnosing pleural TB. Bacteriological examination (smear/culture), tuberculin skin testing/interferon-γ release assays, biochemical testing, imaging and histopathological/cytological examination are the main modalities. Moreover, nucleic acid amplification tests (NAATs), i.e. loop-mediated isothermal amplification, PCR/multiplex-PCR, nested-PCR, real-time PCR and GeneXpert® MTB/RIF are being utilized. Currently, GeneXpert Ultra, Truenat MTBTM, detection of circulating Mycobacterium tuberculosis (Mtb) cell-free DNA by NAATs, aptamer-linked immobilized sorbent assay and immuno-PCR (I-PCR) have also been exploited. EXPERT OPINION Routine tests are not adequate for effective pleural TB diagnosis. The latest molecular/immunological tests as discussed above, and the other tools, i.e. real-time I-PCR/nanoparticle-based I-PCR and identification of Mtb biomarkers within urinary/serum extracellular vesicles being utilized for pulmonary TB and other EPTB types may also be exploited to diagnose pleural TB. Reliable diagnosis and early therapy would reduce the serious complications associated with pleural TB, i.e. TB empyema, pleural fibrosis, etc.
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Affiliation(s)
- Aishwarya Soni
- Centre for Biotechnology, Maharshi Dayanand University, Rohtak-124001, India.,Department of Biotechnology, Deenbandhu Chhotu Ram University of Science and Technology, Murthal, Sonipat-131039, India
| | - Astha Guliani
- Department of TB & Respiratory Medicine, Pt. BD Postgraduate Institute of Medical Sciences, Rohtak-124001, India
| | - Kiran Nehra
- Department of Biotechnology, Deenbandhu Chhotu Ram University of Science and Technology, Murthal, Sonipat-131039, India
| | - Promod K Mehta
- Centre for Biotechnology, Maharshi Dayanand University, Rohtak-124001, India
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Hwang W, Shimizu M, Lee JW. Role of extracellular vesicles in severe pneumonia and sepsis. Expert Opin Biol Ther 2022; 22:747-762. [PMID: 35418256 PMCID: PMC9971738 DOI: 10.1080/14712598.2022.2066470] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
INTRODUCTION Extracellular vesicles (EV) released constitutively or following external stimuli from structural and immune cells are now recognized as important mediators of cell-to-cell communication. They are involved in the pathogenesis of pneumonia and sepsis, leading causes of acute respiratory distress syndrome (ARDS) where mortality rates remain up to 40%. Multiple investigators have demonstrated that one of the underlying mechanisms of the effects of EVs is through the transfer of EV content to host cells, resulting in apoptosis, inflammation, and permeability in target organs. AREAS COVERED The current review focuses on preclinical research examining the role of EVs released into the plasma and injured alveolus during pneumonia and sepsis. EXPERT OPINION Inflammation is associated with elevated levels of circulating EVs that are released by activated structural and immune cells and can have significant proinflammatory, procoagulant, and pro-permeability effects in critically ill patients with pneumonia and/or sepsis. However, clinical translation of the use of EVs as biomarkers or potential therapeutic targets may be limited by current methodologies used to identify and quantify EVs accurately (whether from host cells or infecting organisms) and lack of understanding of the role of EVs in the reparative phase during recovery from pneumonia and/or sepsis.
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Affiliation(s)
- Wonjung Hwang
- Department of Anesthesiology and Pain Medicine, Seoul St. Mary’s hospital, Catholic College of Medicine, The Catholic University of Korea, Republic of Korea
| | - Masaru Shimizu
- Department of Anesthesiology, University of California, San Francisco, San Francisco, California
| | - Jae-Woo Lee
- Department of Anesthesiology, University of California, San Francisco, San Francisco, California.,Jae-Woo Lee, MD, Professor, University of California San Francisco, Department of Anesthesiology, 505 Parnassus Ave., Box 0648, San Francisco, CA 94143, Telephone: (415) 476-0452, Fax: (415) 514-2999,
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Pattnaik B, Patnaik N, Mittal S, Mohan A, Agrawal A, Guleria R, Madan K. Micro RNAs as potential biomarkers in tuberculosis: A systematic review. Noncoding RNA Res 2022; 7:16-26. [PMID: 35128217 PMCID: PMC8792429 DOI: 10.1016/j.ncrna.2021.12.005] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Revised: 12/24/2021] [Accepted: 12/29/2021] [Indexed: 12/15/2022] Open
Abstract
Tuberculosis (TB) remains a major infectious disease across the globe. With increasing TB infections and a rise in multi-drug resistance, rapid diagnostic modalities are required to achieve TB control. Radiological investigations and microbiological tests (microscopic examination, cartridge-based nucleic acid amplification tests, and cultures) are most commonly used to diagnose TB. Histopathological/cytopathological examinations are also required for an accurate diagnosis in many patients. The causative agent, Mycobacterium tuberculosis (Mtb), is known to circumvent the host's immune system. Circulating microRNAs (miRNAs) play a crucial role in biological pathways and can be used as a potential biomarker to detect tuberculosis. miRNAs are small non-coding RNAs and negatively regulate gene expression during post-transcriptional regulation. The differential expression of miRNAs in multiple clinical samples in tuberculosis patients may be helpful as potential disease biomarkers. This review summarizes the literature on miRNAs in various clinical samples as biomarkers for TB diagnosis.
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Affiliation(s)
- Bijay Pattnaik
- Department of Pulmonary, Critical Care and Sleep Medicine, All India Institute of Medical Sciences (AIIMS), New Delhi, India
| | - Niharika Patnaik
- Centre of Excellence in Asthma & Lung Disease, Molecular Immunogenetics Lab, CSIR-Institute of Genomics & Integrative Biology, New Delhi, India
| | - Saurabh Mittal
- Department of Pulmonary, Critical Care and Sleep Medicine, All India Institute of Medical Sciences (AIIMS), New Delhi, India
| | - Anant Mohan
- Department of Pulmonary, Critical Care and Sleep Medicine, All India Institute of Medical Sciences (AIIMS), New Delhi, India
| | - Anurag Agrawal
- Centre of Excellence in Asthma & Lung Disease, Molecular Immunogenetics Lab, CSIR-Institute of Genomics & Integrative Biology, New Delhi, India
| | - Randeep Guleria
- Department of Pulmonary, Critical Care and Sleep Medicine, All India Institute of Medical Sciences (AIIMS), New Delhi, India
| | - Karan Madan
- Department of Pulmonary, Critical Care and Sleep Medicine, All India Institute of Medical Sciences (AIIMS), New Delhi, India
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19
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Magdalena D, Magdalena G. Biological functions and diagnostic implications of microRNAs in Mycobacterium tuberculosis infection. Asian Pac J Trop Biomed 2022. [DOI: 10.4103/2221-1691.333208] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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20
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Saviana M, Romano G, Le P, Acunzo M, Nana-Sinkam P. Extracellular Vesicles in Lung Cancer Metastasis and Their Clinical Applications. Cancers (Basel) 2021; 13:5633. [PMID: 34830787 PMCID: PMC8616161 DOI: 10.3390/cancers13225633] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Revised: 11/04/2021] [Accepted: 11/09/2021] [Indexed: 12/11/2022] Open
Abstract
Extracellular vesicles (EVs) are heterogenous membrane-encapsulated vesicles secreted by every cell into the extracellular environment. EVs carry bioactive molecules, including proteins, lipids, DNA, and different RNA forms, which can be internalized by recipient cells, thus altering their biological characteristics. Given that EVs are commonly found in most body fluids, they have been widely described as mediators of communication in several physiological and pathological processes, including cancer. Moreover, their easy detection in biofluids makes them potentially useful candidates as tumor biomarkers. In this manuscript, we review the current knowledge regarding EVs and non-coding RNAs and their role as drivers of the metastatic process in lung cancer. Furthermore, we present the most recent applications for EVs and non-coding RNAs as cancer therapeutics and their relevance as clinical biomarkers.
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Affiliation(s)
- Michela Saviana
- Department of Internal Medicine, Division of Pulmonary Diseases and Critical Care Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA; (M.S.); (G.R.); (P.L.); (M.A.)
- Department of Molecular Medicine, University La Sapienza, 00161 Rome, Italy
| | - Giulia Romano
- Department of Internal Medicine, Division of Pulmonary Diseases and Critical Care Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA; (M.S.); (G.R.); (P.L.); (M.A.)
| | - Patricia Le
- Department of Internal Medicine, Division of Pulmonary Diseases and Critical Care Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA; (M.S.); (G.R.); (P.L.); (M.A.)
| | - Mario Acunzo
- Department of Internal Medicine, Division of Pulmonary Diseases and Critical Care Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA; (M.S.); (G.R.); (P.L.); (M.A.)
| | - Patrick Nana-Sinkam
- Department of Internal Medicine, Division of Pulmonary Diseases and Critical Care Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA; (M.S.); (G.R.); (P.L.); (M.A.)
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21
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Kuracha MR, Thomas P, Tobi M, McVicker BL. Role of cell-free network communication in alcohol-associated disorders and liver metastasis. World J Gastroenterol 2021; 27:7080-7099. [PMID: 34887629 PMCID: PMC8613644 DOI: 10.3748/wjg.v27.i41.7080] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2021] [Revised: 07/02/2021] [Accepted: 09/30/2021] [Indexed: 02/06/2023] Open
Abstract
The aberrant use of alcohol is a major factor in cancer progression and metastasis. Contributing mechanisms include the systemic effects of alcohol and the exchange of bioactive molecules between cancerous and non-cancerous cells along the brain-gut-liver axis. Such interplay leads to changes in molecular, cellular, and biological functions resulting in cancer progression. Recent investigations have examined the role of extracellular vesicles (EVs) in cancer mechanisms in addition to their contribution as diagnostic biomarkers. Also, EVs are emerging as novel cell-free mediators in pathophysiological scenarios including alcohol-mediated gut microbiome dysbiosis and the release of nanosized EVs into the circulatory system. Interestingly, EVs in cancer patients are enriched with oncogenes, miRNA, lipids, and glycoproteins whose delivery into the hepatic microenvironment may be enhanced by the detrimental effects of alcohol. Proof-of-concept studies indicate that alcohol-associated liver disease is impacted by the effects of exosomes, including altered immune responses, reprogramming of stromal cells, and remodeling of the extracellular matrix. Moreover, the culmination of alcohol-related changes in the liver likely contributes to enhanced hepatic metastases and poor outcomes for cancer patients. This review summarizes the numerous aspects of exosome communications between organs with emphasis on the relationship of EVs in alcohol-associated diseases and cancer metastasis. The potential impact of EV cargo and release along a multi-organ axis is highly relevant to the promotion of tumorigenic mechanisms and metastatic disease. It is hypothesized that EVs target recipient tissues to initiate the formation of prometastatic niches and cancer progression. The study of alcohol-associated mechanisms in metastatic cancers is expected to reveal a better understanding of factors involved in the growth of secondary malignancies as well as novel approaches for therapeutic interventions.
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Affiliation(s)
- Murali R Kuracha
- Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, United States
| | - Peter Thomas
- Department of Surgery, Creighton University School of Medicine, Omaha, NE 68178, United States
| | - Martin Tobi
- Research and Development Service, Detroit VAMC, Detroit, MI 48201, United States
- Department of Medicine, Central Michigan University College of Medicine, Detroit, MI 48201, United States
| | - Benita L McVicker
- Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, United States
- Research Service, Nebraska-Western Iowa Health Care System, Omaha, NE 68105, United States
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Zhu Q, Li Y, Li L, Guo M, Zou C, Xu Y, Yang Z. MicroRNA-889-3p restrains the proliferation and epithelial-mesenchymal transformation of lung cancer cells via down-regulation of Homeodomain-interacting protein kinase 1. Bioengineered 2021; 12:10945-10958. [PMID: 34723781 PMCID: PMC8810057 DOI: 10.1080/21655979.2021.2000283] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
Dysregulated microRNAs (miRNAs) are common in human cancers and are involved in the proliferation, promotion, and metastasis of tumor cells. Therefore, the aim of this study was to evaluate the expression and biological function of miR-889-3p in lung cancer (LC). MiR-889-3p and Homeodomain-interacting protein kinase 1 (HIPK1) expression was detected in human LC tissues and cells. The correlation of miR-889-3p with the clinicopathology of LC patients was observed. After the transfection of miR-889-3p and HIPK1-related plasmids in human LC cell line A549, several studies were employed for detection of cell growth. In addition, the targeting of miR-889-3p with HIPK1 was verified. The results clarified miR-889-3p was down-regulated, while HIPK1 was up-regulated in LC tissues. Elevated miR-889-3p or repressed HIPK1 weakened the viability, epithelial–mesenchymal transition (EMT), invasion, migration of LC cells, whereas strengthened apoptosis. MiR-889-3p targeted HIPK1; MiR-889-3p mediated HIPK1 to affect the proliferation and EMT of LC cells. Therefore, it is concluded that miR-889-3p repressing HIPK1 restrains the proliferation and EMT of LC cells, providing a novel target for LC therapy.
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Affiliation(s)
- Qiang Zhu
- Department of Respiratory Medicine, The First Medical Center of Chinese Pla General Hospital, Beijing, China
| | - Yun Li
- Department of Respiratory Medicine, The Eighth Medical Center of Pla General Hospital, Beijing, China
| | - Lina Li
- Department of Respiratory Medicine, The First Medical Center of Chinese Pla General Hospital, Beijing, China
| | - Mingxue Guo
- Department of Respiratory Medicine, The First Medical Center of Chinese Pla General Hospital, Beijing, China
| | - Chenxi Zou
- Department of Respiratory Medicine, The First Medical Center of Chinese Pla General Hospital, Beijing, China
| | - Yi Xu
- Department of Respiratory Medicine, The First Medical Center of Chinese Pla General Hospital, Beijing, China
| | - Zhen Yang
- Department of Respiratory Medicine, The First Medical Center of Chinese Pla General Hospital, Beijing, China
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Abstract
The transmission of information between tumor cells and other cell types in the tumor microenvironment plays an important role in tumor metastasis and is critically modulated by exosomes and other mediators. Tumor-derived exosomes can promote epithelial-mesenchymal transition, angiogenesis, immune escape, formation of the pre-metastatic microenvironment, and transmission of drug-resistant molecules, thereby promoting tumor growth, invasion, and metastasis. Integrins are important regulatory molecules on exosomes that can locate metastatic cells at the initial stage of metastasis and show good organotropism. This fact suggests that a clear understanding of the roles of exosomal integrins will be beneficial for future clinical applications. Follow-up studies on exosomes using continuously updated purification techniques and identification methods are extremely important. In addition to their potential as cancer biomarkers, exosomes also provide new research directions for precision medicine. Currently, exosomes have potential value in disease treatment and provide clinicians with more meaningful judgment standards.
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24
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Jung AL, Schmeck B, Wiegand M, Bedenbender K, Benedikter BJ. The clinical role of host and bacterial-derived extracellular vesicles in pneumonia. Adv Drug Deliv Rev 2021; 176:113811. [PMID: 34022269 DOI: 10.1016/j.addr.2021.05.021] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Revised: 04/10/2021] [Accepted: 05/18/2021] [Indexed: 12/14/2022]
Abstract
Pneumonia is among the leading causes of morbidity and mortality worldwide. Due to constant evolution of respiratory bacteria and viruses, development of drug resistance and emerging pathogens, it constitutes a considerable health care threat. To enable development of novel strategies to control pneumonia, a better understanding of the complex mechanisms of interaction between host cells and infecting pathogens is vital. Here, we review the roles of host cell and bacterial-derived extracellular vesicles (EVs) in these interactions. We discuss clinical and experimental as well as pathogen-overarching and pathogen-specific evidence for common viral and bacterial elicitors of community- and hospital-acquired pneumonia. Finally, we highlight the potential of EVs for improved management of pneumonia patients and discuss the translational steps to be taken before they can be safely exploited as novel vaccines, biomarkers, or therapeutics in clinical practice.
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25
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Exosomes in Lung Cancer: Actors and Heralds of Tumor Development. Cancers (Basel) 2021; 13:cancers13174330. [PMID: 34503141 PMCID: PMC8431734 DOI: 10.3390/cancers13174330] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Revised: 08/24/2021] [Accepted: 08/25/2021] [Indexed: 12/16/2022] Open
Abstract
Lung cancer is a leading cause of cancer-related death worldwide and in most cases, diagnosis is reached when the tumor has already spread and prognosis is quite poor. For that reason, the research for new biomarkers that could improve early diagnosis and its management is essential. Exosomes are microvesicles actively secreted by cells, especially by tumor cells, hauling molecules that mimic molecules of the producing cells. There are multiple methods for exosome isolation and analysis, although not standardized, and cancer exosomes from biological fluids are especially difficult to study. Exosomes' cargo proteins, RNA, and DNA participate in the communication between cells, favoring lung cancer development by delivering signals for growth, metastasis, epithelial mesenchymal transition, angiogenesis, immunosuppression and even drug resistance. Exosome analysis can be useful as a type of liquid biopsy in the diagnosis, prognosis and follow-up of lung cancer. In this review, we will discuss recent advances in the role of exosomes in lung cancer and their utility as liquid biopsy, with special attention to isolating methods.
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26
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Xia L, Zhu G, Huang H, He Y, Liu X. LncRNA small nucleolar RNA host gene 16 (SNHG16) silencing protects lipopolysaccharide (LPS)-induced cell injury in human lung fibroblasts WI-38 through acting as miR-141-3p sponge. Biosci Biotechnol Biochem 2021; 85:1077-1087. [PMID: 33836533 DOI: 10.1093/bbb/zbab016] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2020] [Accepted: 01/21/2021] [Indexed: 12/14/2022]
Abstract
Long noncoding RNA (LncRNA) small nucleolar RNA host gene 16 (SNHG16) is correlated with cell injuries, including pneumonia. However, its role and mechanism remain vague in pneumonia. The interplay among genes was confirmed by dual-luciferase reporter assay, RNA immunoprecipitation, and RNA pull-down assay. SNHG16 and sushi domain containing 2 (SUSD2) were upregulated, and miRNA (miR)-141-3p was downregulated in the serum of acute pneumonia patients and lipopolysaccharide (LPS)-challenged human lung fibroblasts WI-38. LPS induced apoptosis, autophagy, and inflammatory response in WI-38 cells, which was significantly attenuated by SNHG16 knockdown and/or miR-141-3p overexpression. Notably, both SNHG16 and SUSD2 were identified as target genes of miR-141-3p. Besides, the suppressive role of SNHG16 knockdown in LPS-induced in WI-38 cells was partially abolished by miR-141-3p silencing, and the similar inhibition of miR-141-3p overexpression was further blocked by SUSD2 restoration. In conclusion, knockdown of SNHG16 could alleviate LPS-induced apoptosis, autophagy, and inflammation in WI-38 cells partially though the SNHG16/miR-141-3p/SUSD2 pathway.
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Affiliation(s)
- Lei Xia
- Department of Pediatrics, Binzhou People's Hospital, Binzhou, Shandong, China
| | - Guoqing Zhu
- Department of Pediatrics, Binzhou People's Hospital, Binzhou, Shandong, China
| | - Haiyun Huang
- Department of oral and maxillofacial surgery, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, Shandong, China
| | - Yishui He
- Department of Stomatology, Shenzhen Hospital of Southern Medical University, Shenzhen, China
| | - Xingguang Liu
- Department of oral and maxillofacial surgery, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, Shandong, China
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27
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Zhu LR, Yuan RX, Xia XB, Wang Y, Zhu YM, Fi L, Li J. Assessment of a panel of miRNAs in serum and pleural fluid for the differential diagnosis of malignant and benign pleural effusion. Cancer Biomark 2021; 33:71-82. [PMID: 34366325 DOI: 10.3233/cbm-210090] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Differential diagnosis between malignant pleural effusion (MPE) and benign pleural effusion (BPE) remains a clinical challenge. OBJECTIVE The aim of the study is to assess the efficacy of the serum and pleural fluid (PF) miRNA panels in distinguishing MPE from BPE. METHODS Fourteen candidate miRNAs which were shown aberrant expression in lung cancer based on previous studies were tested by quantitative real-time PCR (qRT-PCR) in 20 MPE patients and 20 BPE patients. Significantly aberrantly expressed miRNAs were further assessed by qRT-PCR in all patients enrolled in this study. A receiver operating characteristic (ROC) curve was constructed, and the area under the ROC curve (AUC) was calculated to evaluated the diagnostic performance of the miRNAs. RESULTS miR-21, miR-29c and miR-182 were found to be significantly aberrantly expressed in the serum and PF of MPE patients. The AUCs for the combination of miR-21, miR-29c and miR-182 in serum and PF were 0.832 and 0.89 respectively in distinguishing MPE from infection-associated PE including tuberculous pleurisy and parapneumonia PE, and 0.866 and 0.919 respectively for differentiating MPE from heart failure-associated PE, which were superior to AUC of each individual miRNAs. CONCLUSIONS miR-21, miR-29c and miR-182 in serum and PF could be useful biomarkers for MPE of diagnosis.
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Affiliation(s)
- Li-Rong Zhu
- Department of Pulmonary Medicine, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China.,Department of Pulmonary Medicine, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China
| | - Rong-Xia Yuan
- Department of Pulmonary Medicine, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China.,Department of Respiratory Disease, Yancheng Third People's Hospital, Yancheng, Jiangsu, China.,Department of Pulmonary Medicine, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China
| | - Xian-Bin Xia
- Department of Pulmonary Medicine, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China
| | - Yi Wang
- Center of Experimental Medicine, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China
| | - Yu-Min Zhu
- Department of Pulmonary Medicine, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China
| | - Ling Fi
- Department of Pulmonary Medicine, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China
| | - Jian Li
- Department of Pulmonary Medicine, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China
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Diving into the Pleural Fluid: Liquid Biopsy for Metastatic Malignant Pleural Effusions. Cancers (Basel) 2021; 13:cancers13112798. [PMID: 34199799 PMCID: PMC8200094 DOI: 10.3390/cancers13112798] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Revised: 06/03/2021] [Accepted: 06/03/2021] [Indexed: 12/18/2022] Open
Abstract
Simple Summary Malignant pleural effusion is a common complication arising as the natural progression of many tumors, such as lung cancer. When this occurs, the common protocol consists of analyzing the pleural fluid for the presence of malignant cells. However, on many occasions no malignant cells are found despite a clear suspicion of cancer. Thus, the current diagnostic methodology is imperfect and more precise methods for the identification of malignancy are needed. Nonetheless, these methods are often invasive, which may be counterproductive, especially for patients with poor health condition. These concerns have made clinicians consider alternative non-invasive strategies to diagnose cancer using the generally abundant pleural fluid (e.g., liquid biopsy). Thus, a liquid sample can be analyzed for the presence of cancer footprints, such as circulating malignant cells and tumor nucleic acids. Herein, we review the literature for studies considering pleural fluid as a successful source of liquid biopsy. Abstract Liquid biopsy is emerging as a promising non-invasive diagnostic tool for malignant pleural effusions (MPE) due to the low sensitivity of conventional pleural fluid (PF) cytological examination and the difficulty to obtain tissue biopsies, which are invasive and require procedural skills. Currently, liquid biopsy is increasingly being used for the detection of driver mutations in circulating tumor DNA (ctDNA) from plasma specimens to guide therapeutic interventions. Notably, malignant PF are richer than plasma in tumor-derived products with potential clinical usefulness, such as ctDNA, micro RNAs (miRNAs) and long non-coding RNAs (lncRNAs), and circulating tumor cells (CTC). Tumor-educated cell types, such as platelets and macrophages, have also been added to this diagnostic armamentarium. Herein, we will present an overview of the role of the preceding biomarkers, collectively known as liquid biopsy, in PF samples, as well as the main technical approaches used for their detection and quantitation, including a proper sample processing. Technical limitations of current platforms and future perspectives in the field will also be addressed. Using PF as liquid biopsy shows promise for use in current practice to facilitate the diagnosis and management of metastatic MPE.
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29
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Extracellular Vesicles as a Novel Liquid Biopsy-Based Diagnosis for the Central Nervous System, Head and Neck, Lung, and Gastrointestinal Cancers: Current and Future Perspectives. Cancers (Basel) 2021; 13:cancers13112792. [PMID: 34205183 PMCID: PMC8200014 DOI: 10.3390/cancers13112792] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 05/28/2021] [Accepted: 06/02/2021] [Indexed: 12/11/2022] Open
Abstract
Simple Summary To improve clinical outcomes, early diagnosis is mandatory in cancer patients. Several diagnostic approaches have been proposed, however, the main drawback relies on the invasive procedures required. Extracellular vesicles (EVs) are bilayer lipid membrane structures released by almost all cells and transferred to remote sites via the bloodstream. The observation that their cargo reflects the cell of origin has opened a new frontier for non-invasive biomarker discovery in oncology. Moreover, since EVs can be recovered from different body fluids, their impact as a Correctdiagnostic tool has gained particular interest. Hence, in the last decade, several studies using different biological fluids have been performed, showing the valuable contributions of EVs as tumour biomarkers, and their improved diagnostic power when combined with currently available tumour markers. In this review, the most relevant data on the diagnostic relevance of EVs, alone or in combination with the well-established tumour markers, are discussed. Abstract Early diagnosis, along with innovative treatment options, are crucial to increase the overall survival of cancer patients. In the last decade, extracellular vesicles (EVs) have gained great interest in biomarker discovery. EVs are bilayer lipid membrane limited structures, released by almost all cell types, including cancer cells. The EV cargo, which consists of RNAs, proteins, DNA, and lipids, directly mirrors the cells of origin. EVs can be recovered from several body fluids, including blood, cerebral spinal fluid (CSF), saliva, and Broncho-Alveolar Lavage Fluid (BALF), by non-invasive or minimally invasive approaches, and are therefore proposed as feasible cancer diagnostic tools. In this review, methodologies for EV isolation and characterization and their impact as diagnostics for the central nervous system, head and neck, lung, and gastrointestinal cancers are outlined. For each of these tumours, recent data on the potential clinical applications of the EV’s unique cargo, alone or in combination with currently available tumour biomarkers, have been deeply discussed.
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30
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Duréndez-Sáez E, Torres-Martinez S, Calabuig-Fariñas S, Meri-Abad M, Ferrero-Gimeno M, Camps C. Exosomal microRNAs in non-small cell lung cancer. Transl Cancer Res 2021; 10:3128-3139. [PMID: 35116621 PMCID: PMC8798604 DOI: 10.21037/tcr-20-2815] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Accepted: 12/10/2020] [Indexed: 12/14/2022]
Abstract
Lung cancer is one of the highest incidence cancer types worldwide and one with the lowest 5-year survival rate of all cancer types. Despite recent insights into lung cancer pathobiology, including novel biomarker-targeted therapies and immunotherapies, most of lung patients are diagnosed at late stages with limited and ineffective treatments. Therefore, more approaches are needed to eradicate lung cancer. In the last years, small extracellular vesicles (EVs) secreted by tumor cells have been gaining relevance. These intercellular signal mediators, called exosomes, contain a huge range of biological elements, including lipids, nucleic acids and miRNAs, among others, that carry relevant information. The role of exosomes in cancer progression is dependent on cancer type, molecular characteristics and stage. MicroRNAs molecules are a big part of the content of exosomes cargo and probably the most studied ones. Due to the regulatory role in gene expression, miRNAs may provide information of the molecular characteristics of the tumor and be also able to reprogram distant target cells. Exosomal miRNAs can modulate different biological processes in cancer such as growth, progression, invasion, angiogenesis, metastasis and drug resistance; playing a critical role in modifying the microenvironment of non-small cell lung cancer (NSCLC). Therefore, they can act by regulating tumor resistance and also be useful to monitoring the response/relapse to targeted therapies. In this work, we summarize the relevant advances on the potential role of exosomal miRNAs in NSCLC pathobiogenesis, highlighting the clinical utility of exosomal microRNAs as biomarkers for the NSCLC diagnosis, prognosis, drug resistance and therapeutic strategies.
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Affiliation(s)
- Elena Duréndez-Sáez
- Molecular Oncology Laboratory, Fundación Hospital General Universitario de Valencia, Valencia, Spain.,CIBERONC, Valencia, Spain
| | - Susana Torres-Martinez
- Molecular Oncology Laboratory, Fundación Hospital General Universitario de Valencia, Valencia, Spain.,CIBERONC, Valencia, Spain
| | - Silvia Calabuig-Fariñas
- Molecular Oncology Laboratory, Fundación Hospital General Universitario de Valencia, Valencia, Spain.,CIBERONC, Valencia, Spain.,Department of Pathology, Universitat de València, Valencia, Spain
| | - Marina Meri-Abad
- Department of Medical Oncology, Hospital General Universitario de Valencia, Valencia, Spain
| | - Macarena Ferrero-Gimeno
- Molecular Oncology Laboratory, Fundación Hospital General Universitario de Valencia, Valencia, Spain.,CIBERONC, Valencia, Spain
| | - Carlos Camps
- Molecular Oncology Laboratory, Fundación Hospital General Universitario de Valencia, Valencia, Spain.,CIBERONC, Valencia, Spain.,Department of Medical Oncology, Hospital General Universitario de Valencia, Valencia, Spain.,Department of Medicine, Universitat de València, Valencia, Spain
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31
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Bi H, Ren D, Zhang J, Wang H. [Advances in Exosomes in the Pathogenesis and Diagnosis of Lung Cancer]. ZHONGGUO FEI AI ZA ZHI = CHINESE JOURNAL OF LUNG CANCER 2021; 23:589-596. [PMID: 32702793 PMCID: PMC7406446 DOI: 10.3779/j.issn.1009-3419.2020.104.18] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The incidence of lung cancer is high worldwide, and lung cancer is the leading cause of death from malignant tumors in both men and women. Early diagnosis of lung cancer can significantly improve the patient's prognosis. Therefore, searching for specific markers to assist in the early diagnosis of lung cancer is urgent question. Exosomes are nano-sized microvesicles and contain various biomaterial, including nucleic acids, proteins, and lipids. Exosomes are important carriers of these biomaterial, serve important roles in intracellular communications and signal transduction among tissues. Due to its unique enrichment mechanism, it has the stability and specificity as a biomarker. Exosomes are not only involved in the formation of tumor microenvironment and new blood vessels in lung cancer, but also involved in chemotherapy, targeted therapy response and prognosis assessment. Many research advances bring new hope for prolonging the survival of lung cancer patients. This article reviews the value of exosome specific protein and microRNA (miRNA) in lung cancer in the diagnosis and prognosis of lung cancer.
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Affiliation(s)
- Huanhuan Bi
- Department of Respiratory and Critical Care Medcine, The Affiliated Hospital of Qingdao University, Qingdao 266000, China
| | - Dunqiang Ren
- Department of Respiratory and Critical Care Medcine, The Affiliated Hospital of Qingdao University, Qingdao 266000, China
| | - Jun Zhang
- Department of Respiratory and Critical Care Medcine, The Affiliated Hospital of Qingdao University, Qingdao 266000, China
| | - Hongmei Wang
- Department of Respiratory and Critical Care Medcine, The Affiliated Hospital of Qingdao University, Qingdao 266000, China
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Antonopoulos D, Tsilioni I, Tsiara S, Moustaka E, Ladias S, Perlepe G, Theoharides TC, Gourgoulianis KI, Balatsos NAA. ExoProK: A Practical Method for the Isolation of Small Extracellular Vesicles from Pleural Effusions. Methods Protoc 2021; 4:mps4020031. [PMID: 34065021 PMCID: PMC8163155 DOI: 10.3390/mps4020031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Revised: 04/19/2021] [Accepted: 04/19/2021] [Indexed: 11/16/2022] Open
Abstract
Extracellular vesicles (EVs) are cell-secreted, lipid membrane-enclosed nanoparticles without functional nucleus. EV is a general term that includes various subtypes of particles named microvesicles, microparticles, ectosomes or exosomes. EVs transfer RNA, DNA and protein cargo between proximal and distant cells and tissues, thus constituting an organism-wide signal transduction network. Pathological tissues secrete EVs that differ in their cargo composition compared to their healthy counterparts. The detection of biomarkers in EVs from biological fluids may aid the diagnosis of disease and/or monitor its progression in a minimally invasive manner. Among biological fluids, pleural effusions (PEs) are integrated to clinical practice, as they accompany a wide variety of lung disorders. Due to the proximity with the pleura and the lungs, PEs are expected to be especially enriched in EVs that originate from diseased tissues. However, PEs are among the least studied biofluids regarding EV-specialized isolation methods and related biomarkers. Herein, we describe a practical EV isolation method from PEs for the screening of EV RNA biomarkers in clinical routine. It is based on a Proteinase K treatment step to digest contaminants prior to standard polyethylene-glycol precipitation. The efficiency of the method was confirmed by transmission electron microscopy, nanoparticle tracking analysis and Western blot. The reliability and sensitivity of the method towards the detection of EV-enriched RNA biomarkers from multiple PEs was also demonstrated.
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Affiliation(s)
- Dionysios Antonopoulos
- Department of Biochemistry and Biotechnology, University of Thessaly, Viopolis, 415 00 Larissa, Greece; (D.A.); (S.T.); (E.M.)
| | - Irene Tsilioni
- Department of Immunology, Tufts University School of Medicine, 136 Harrison Avenue, Suite J304, Boston, MA 02111, USA; (I.T.); (T.C.T.)
| | - Sophia Tsiara
- Department of Biochemistry and Biotechnology, University of Thessaly, Viopolis, 415 00 Larissa, Greece; (D.A.); (S.T.); (E.M.)
| | - Eirini Moustaka
- Department of Biochemistry and Biotechnology, University of Thessaly, Viopolis, 415 00 Larissa, Greece; (D.A.); (S.T.); (E.M.)
| | - Spyridon Ladias
- Respiratory Medicine Department, Faculty of Medicine, University of Thessaly, Viopolis, 411 10 Larissa, Greece; (S.L.); (G.P.)
| | - Garyfallia Perlepe
- Respiratory Medicine Department, Faculty of Medicine, University of Thessaly, Viopolis, 411 10 Larissa, Greece; (S.L.); (G.P.)
| | - Theoharis C. Theoharides
- Department of Immunology, Tufts University School of Medicine, 136 Harrison Avenue, Suite J304, Boston, MA 02111, USA; (I.T.); (T.C.T.)
| | - Konstantinos I. Gourgoulianis
- Respiratory Medicine Department, Faculty of Medicine, University of Thessaly, Viopolis, 411 10 Larissa, Greece; (S.L.); (G.P.)
- Correspondence: (K.I.G.); (N.A.A.B.)
| | - Nikolaos A. A. Balatsos
- Department of Biochemistry and Biotechnology, University of Thessaly, Viopolis, 415 00 Larissa, Greece; (D.A.); (S.T.); (E.M.)
- Correspondence: (K.I.G.); (N.A.A.B.)
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Freitas C, Sousa C, Machado F, Serino M, Santos V, Cruz-Martins N, Teixeira A, Cunha A, Pereira T, Oliveira HP, Costa JL, Hespanhol V. The Role of Liquid Biopsy in Early Diagnosis of Lung Cancer. Front Oncol 2021; 11:634316. [PMID: 33937034 PMCID: PMC8085425 DOI: 10.3389/fonc.2021.634316] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Accepted: 03/19/2021] [Indexed: 12/12/2022] Open
Abstract
Liquid biopsy is an emerging technology with a potential role in the screening and early detection of lung cancer. Several liquid biopsy-derived biomarkers have been identified and are currently under ongoing investigation. In this article, we review the available data on the use of circulating biomarkers for the early detection of lung cancer, focusing on the circulating tumor cells, circulating cell-free DNA, circulating micro-RNAs, tumor-derived exosomes, and tumor-educated platelets, providing an overview of future potential applicability in the clinical practice. While several biomarkers have shown exciting results, diagnostic performance and clinical applicability is still limited. The combination of different biomarkers, as well as their combination with other diagnostic tools show great promise, although further research is still required to define and validate the role of liquid biopsies in clinical practice.
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Affiliation(s)
- Cláudia Freitas
- Department of Pulmonology, Centro Hospitalar e Universitário São João, Porto, Portugal
- Faculty of Medicine, University of Porto, Porto, Portugal
| | - Catarina Sousa
- Department of Pulmonology, Centro Hospitalar e Universitário São João, Porto, Portugal
| | - Francisco Machado
- Department of Pulmonology, Centro Hospitalar e Universitário São João, Porto, Portugal
| | - Mariana Serino
- Department of Pulmonology, Centro Hospitalar e Universitário São João, Porto, Portugal
| | - Vanessa Santos
- Department of Pulmonology, Centro Hospitalar e Universitário São João, Porto, Portugal
| | - Natália Cruz-Martins
- Faculty of Medicine, University of Porto, Porto, Portugal
- Laboratory of Neuropsychophysiology, Faculty of Psychology and Education Sciences, University of Porto, Porto, Portugal
- Institute for Research and Innovation in Health (i3S), University of Porto, Porto, Portugal
| | - Armando Teixeira
- Institute for Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal
- Faculty of Engineering, University of Porto, Porto, Portugal
| | - António Cunha
- Institute for Systems and Computer Engineering, Technology and Science (INESC TEC), Porto, Portugal
- Department of Engineering, University of Trás-os-Montes and Alto Douro, Vila Real, Portugal
| | - Tania Pereira
- Institute for Systems and Computer Engineering, Technology and Science (INESC TEC), Porto, Portugal
| | - Hélder P. Oliveira
- Institute for Systems and Computer Engineering, Technology and Science (INESC TEC), Porto, Portugal
- Faculty of Sciences, University of Porto, Porto, Portugal
| | - José Luís Costa
- Faculty of Medicine, University of Porto, Porto, Portugal
- Institute for Research and Innovation in Health (i3S), University of Porto, Porto, Portugal
- Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal
| | - Venceslau Hespanhol
- Department of Pulmonology, Centro Hospitalar e Universitário São João, Porto, Portugal
- Faculty of Medicine, University of Porto, Porto, Portugal
- Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal
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Xu S, Zheng L, Kang L, Xu H, Gao L. microRNA-let-7e in serum-derived exosomes inhibits the metastasis of non-small-cell lung cancer in a SUV39H2/LSD1/CDH1-dependent manner. Cancer Gene Ther 2021; 28:250-264. [PMID: 33299140 DOI: 10.1038/s41417-020-00216-1] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2020] [Revised: 08/03/2020] [Accepted: 08/17/2020] [Indexed: 11/09/2022]
Abstract
Non-small-cell lung cancer (NSCLC) remains the leading cause of cancer-related death worldwide. Accumulating research has highlighted the ability of exosome-encapsulated microRNAs (miRNAs or miRs) as potential circulating biomarkers for lung cancer. The current study aimed to evaluate the clinical significance of serum-derived exosomal miR-let-7e as a biomarker in the metastasis of NSCLC. Initially, the expression of miR-let-7e, SUV39H2, and CDH1 in human NSCLC tissues and exosomes isolated from the serum of NSCLC patients was determined by RT-qPCR, demonstrating that miR-let-7e was downregulated in NSCLC tissues and serum-derived exosomes, while SUV39H2 was upregulated in NSCLC tissues. Kaplan-Meier method revealed that both lower miR-let-7e expression and higher SUV39H2 expression were correlated with a lower survival rate of NSCLC patients. Next, SUV39H2 was predicted and validated to be a target of miR-let-7e using dual-luciferase reporter assay. NSCLC H1299 cells following ectopic expression and depletion experiments of miR-let-7e and SUV39H2 were treated with serum-derived exosomes, after which the viability, migration, and invasion of H1299 cells were detected using CCK-8 and Transwell assays. Further, in vivo experiments were conducted to elucidate the effect of exosomal miR-let-7e on tumorigenesis. Results revealed that miR-let-7e overexpression in serum-derived exosomes inhibited SUV39H2, resulting in impaired cell viability, migration, and invasion in vitro as well as delayed tumor growth in vivo. In conclusion, the key findings of the current study demonstrate that exosomal miR-let-7e from serum possesses anticarcinogenic properties against NSCLC via the SUV39H2/LSD1/CDH1 axis.
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Affiliation(s)
- Shufeng Xu
- Department of Respiratory, The First Hospital of Qinhuangdao, Qinhuangdao, 066000, PR China
| | - Lei Zheng
- Department of Oncology, The First Hospital of Qinhuangdao, Qinhuangdao, 066000, PR China
| | - Liying Kang
- Department of Oncology, Tianjin Wuqing District People's Hospital, Tianjin, 301700, PR China
| | - Hongmei Xu
- Department of Oncology, The First Hospital of Qinhuangdao, Qinhuangdao, 066000, PR China
| | - Liming Gao
- Department of Oncology, The First Hospital of Qinhuangdao, Qinhuangdao, 066000, PR China.
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Mohammadi R, Hosseini SA, Noruzi S, Ebrahimzadeh A, Sahebkar A. Diagnostic and Therapeutic Applications of Exosome Nanovesicles in Lung Cancer: State-of-The-Art. Anticancer Agents Med Chem 2021; 22:83-100. [PMID: 33645488 DOI: 10.2174/1871520621666210301085318] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2020] [Revised: 12/30/2020] [Accepted: 01/13/2021] [Indexed: 11/22/2022]
Abstract
Lung cancer is a malignant disease with a frequency of various morbidity, mortality, and poor prognosis in patients that the conventional therapeutic approaches are not efficient sufficiently. Recently, with the discovery of exosomes, researchers have examined new approaches in the development, diagnosis, treatment, and drug delivery of various cancer, such as lung cancer, and display various its potential. Investigation of exosome-derived lung cancer cells contents and preparation of their exhaustive profile by advanced technics such as labeling exosome with nanoparticle and types of mass spectroscopy methods will assist researchers for take advantage of the specific properties of exosomes. Moreover, scientists will present encouraging ways for the treatment of lung cancer with loaded of drugs, proteins, microRNA, and siRNA in specific antigen targeted exosomes. This manuscript will include brief details on the role of exosomes as a novel prognostic biomarker (by the content of lipid, surface and internal protein, miRNAs, and LnRNAs) and therapeutic agent (as vaccine and targeted drug delivery) in lung cancer.
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Affiliation(s)
- Rezvan Mohammadi
- Student Research Committee, Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran. Iran
| | - Seyede A Hosseini
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad. Iran
| | - Somaye Noruzi
- Department of Biotechnology, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd. Iran
| | - Ailin Ebrahimzadeh
- Natural Products and Medicinal Plants Research Center, North Khorasan University of Medical Science, Bojnurd. Iran
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad. Iran
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36
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Srivastava A, Rathore S, Munshi A, Ramesh R. Extracellular Vesicles in Oncology: from Immune Suppression to Immunotherapy. AAPS J 2021; 23:30. [PMID: 33586060 PMCID: PMC7882565 DOI: 10.1208/s12248-021-00554-4] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Accepted: 01/05/2021] [Indexed: 02/07/2023] Open
Abstract
Exosomes are involved in cell-to-cell communication and play a crucial role in cellular physiology. The role of exosomes in cancer has been widely explored. Tumor cells have evolved and adapted to evade the immune response. The study of the immune system's modulations in favor of rogue tumor cells led to the development of a novel immunotherapeutic strategy targeting the immune checkpoint proteins (ICPs). In clinical settings, the response to ICP therapy has been inconsistent and is difficult to predict. Quantitating the targeted ICPs through immunohistochemistry is one approach, but is not pragmatic in a clinical setting and is often not sensitive. Examining the molecules present in bodily fluids to determine ICP treatment response, "liquid biopsy" is a convenient alternative. The term "liquid biopsy" refers to circulating tumor cells (CTCs), extracellular vesicles (EVs), non-coding (nc) RNA, circulating tumor DNA (ctDNA), circulating free DNA (cfDNA), etc. EVs includes exosomes, microvesicles, and oncosomes. Herein, we focus on exosomes isolated from bodily fluids and their use in liquid biopsy. Due to their unique ability to transfer bioactive molecules and perturb the physiology of recipient cells, exosomes have garnered attention for their immune modulation role and as a resource to identify molecules associated with liquid biopsy-based diagnostic methods. In this review, we examine the putative role of exosomes and their cargo in influencing the immune system. We discuss the immune and tumor cells present in the tumor microenvironment (TME), and the exosomes derived from these cells to understand how they participate in creating the immune-suppressive TME. Additionally, use of exosomes in liquid biopsy-based methods to measure the treatment response elicited by immunotherapy is discussed. Finally, we describe how exosomes have been used to develop immune therapies, especially cell-free vaccines, for cancer treatment.
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Affiliation(s)
- Akhil Srivastava
- Department of Pathology, University of Oklahoma Health Sciences Center, 975 N.E., 10th Street, Oklahoma City, Oklahoma, 73104, USA
- Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, 73104, Oklahoma, USA
| | - Shipra Rathore
- Department of Pathology, University of Oklahoma Health Sciences Center, 975 N.E., 10th Street, Oklahoma City, Oklahoma, 73104, USA
- Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, 73104, Oklahoma, USA
| | - Anupama Munshi
- Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, 73104, Oklahoma, USA
- Department of Radiation Oncology, University of Oklahoma Health Sciences Center, 975 N.E., 10th Street, Oklahoma City, 73104, Oklahoma, USA
| | - Rajagopal Ramesh
- Department of Pathology, University of Oklahoma Health Sciences Center, 975 N.E., 10th Street, Oklahoma City, Oklahoma, 73104, USA.
- Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, 73104, Oklahoma, USA.
- Graduate Program in Biomedical Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, 73104, Oklahoma, USA.
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37
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Ma T, Hu Y, Guo Y, Zhang Q. Human umbilical vein endothelial cells-derived microRNA-203-containing extracellular vesicles alleviate non-small-cell lung cancer progression through modulating the DTL/p21 axis. Cancer Gene Ther 2021; 29:87-100. [PMID: 33558703 DOI: 10.1038/s41417-020-00292-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Revised: 12/03/2020] [Accepted: 12/17/2020] [Indexed: 11/09/2022]
Abstract
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, and is characterized by extensive metastasis and poor prognosis. Extracellular vesicles (EVs) derived from endothelial cells carrying microRNAs (miRNAs/miRs) have diagnostic and therapeutic potential for NSCLC. We herein investigate the potential of EVs derived from human umbilical vein endothelial cells (HUVECs) to transfer miR-203 to affect the progression of NSCLC. miR-203 and p21 were poorly expressed while DTL was highly expressed both in NSCLC tissues and cell lines. We employed CCK-8 proliferation, colony formation, and Transwell migration and invasion assays to evaluate the effects of miR-203 on NSCLC cell behaviors using loss- and gain-function approaches. EVs were isolated from HUVECs and then co-cultured with the A549 cells transfected with mimic-NC or miR-203 inhibitor. miR-203 targeted DTL and downregulated its expression, subsequently leading to increased stability of p21 which is a tumor suppressor. EV-enriched miR-203 from HUVECs suppressed malignant phenotypes of NSCLC cells and delayed tumor growth. In conclusion, miR-203 from HUVEC-derived EVs exerts inhibitory effects on the progression of NSCLC by targeting DTL and promoting p21 protein stability.
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Affiliation(s)
- Tiangang Ma
- Department of Respiratory and Critical Care Medicine, the 2nd Hospital of Jilin University, Changchun, 130021, P.R. China
| | - Yanbing Hu
- Department of Ultrasound, the 2nd Hospital of Jilin University, Changchun, 130021, P.R. China
| | - Yinxue Guo
- Department of Clinical Laboratory, the 2nd Hospital of Jilin University, Changchun, 130021, P.R. China
| | - Qinghua Zhang
- Department of Respiratory and Critical Care Medicine, the 2nd Hospital of Jilin University, Changchun, 130021, P.R. China.
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Rodríguez M, Ajona D, Seijo LM, Sanz J, Valencia K, Corral J, Mesa-Guzmán M, Pío R, Calvo A, Lozano MD, Zulueta JJ, Montuenga LM. Molecular biomarkers in early stage lung cancer. Transl Lung Cancer Res 2021; 10:1165-1185. [PMID: 33718054 PMCID: PMC7947407 DOI: 10.21037/tlcr-20-750] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Low dose computed tomography (LDCT) screening, together with the recent advances in targeted and immunotherapies, have shown to improve non-small cell lung cancer (NSCLC) survival. Furthermore, screening has increased the number of early stage-detected tumors, allowing for surgical resection and multimodality treatments when needed. The need for improved sensitivity and specificity of NSCLC screening has led to increased interest in combining clinical and radiological data with molecular data. The development of biomarkers is poised to refine inclusion criteria for LDCT screening programs. Biomarkers may also be useful to better characterize the risk of indeterminate nodules found in the course of screening or to refine prognosis and help in the management of screening detected tumors. The clinical implications of these biomarkers are still being investigated and whether or not biomarkers will be included in further decision-making algorithms in the context of screening and early lung cancer management still needs to be determined. However, it seems clear that there is much room for improvement even in early stage lung cancer disease-free survival (DFS) rates; thus, biomarkers may be the key to refine risk-stratification and treatment of these patients. Clinicians’ capacity to register, integrate, and analyze all the available data in both high risk individuals and early stage NSCLC patients will lead to a better understanding of the disease’s mechanisms, and will have a direct impact in diagnosis, treatment, and follow up of these patients. In this review, we aim to summarize all the available data regarding the role of biomarkers in LDCT screening and early stage NSCLC from a multidisciplinary perspective. We have highlighted clinical implications, the need to combine risk stratification, clinical data, radiomics, molecular information and artificial intelligence in order to improve clinical decision-making, especially regarding early diagnostics and adjuvant therapy. We also discuss current and future perspectives for biomarker implementation in routine clinical practice.
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Affiliation(s)
- María Rodríguez
- Department of Thoracic Surgery, Clínica Universidad de Navarra, Madrid, Spain
| | - Daniel Ajona
- Program in Solid Tumors, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.,Navarra Institute for Health Research (IdISNA), Pamplona, Spain.,Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.,Department of Biochemistry and Genetics, School of Sciences, University of Navarra, Pamplona, Spain
| | - Luis M Seijo
- Department of Pulmonology, Clínica Universidad de Navarra, Madrid, Spain.,Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), Madrid, Spain
| | - Julián Sanz
- Department of Pathology, Clínica Universidad de Navarra, Madrid, Spain
| | - Karmele Valencia
- Program in Solid Tumors, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.,Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.,Department of Biochemistry and Genetics, School of Sciences, University of Navarra, Pamplona, Spain
| | - Jesús Corral
- Department of Oncology, Clínica Universidad de Navarra, Madrid, Spain
| | - Miguel Mesa-Guzmán
- Department of Thoracic Surgery, Clínica Universidad de Navarra, Pamplona, Spain
| | - Rubén Pío
- Program in Solid Tumors, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.,Navarra Institute for Health Research (IdISNA), Pamplona, Spain.,Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.,Department of Biochemistry and Genetics, School of Sciences, University of Navarra, Pamplona, Spain
| | - Alfonso Calvo
- Program in Solid Tumors, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.,Navarra Institute for Health Research (IdISNA), Pamplona, Spain.,Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.,Department of Pathology, Anatomy and Physiology, Schools of Medicine and Sciences, University of Navarra, Pamplona, Spain
| | - María D Lozano
- Navarra Institute for Health Research (IdISNA), Pamplona, Spain.,Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.,Department of Pathology, Anatomy and Physiology, Schools of Medicine and Sciences, University of Navarra, Pamplona, Spain.,Department of Pathology, Clínica Universidad de Navarra, Pamplona, Spain
| | - Javier J Zulueta
- Navarra Institute for Health Research (IdISNA), Pamplona, Spain.,Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.,Department of Pulmonology, Clínica Universidad de Navarra, Pamplona, Spain
| | - Luis M Montuenga
- Program in Solid Tumors, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.,Navarra Institute for Health Research (IdISNA), Pamplona, Spain.,Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.,Department of Pathology, Anatomy and Physiology, Schools of Medicine and Sciences, University of Navarra, Pamplona, Spain
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Biadglegne F, König B, Rodloff AC, Dorhoi A, Sack U. Composition and Clinical Significance of Exosomes in Tuberculosis: A Systematic Literature Review. J Clin Med 2021; 10:E145. [PMID: 33406750 PMCID: PMC7795701 DOI: 10.3390/jcm10010145] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2020] [Revised: 12/28/2020] [Accepted: 12/29/2020] [Indexed: 12/21/2022] Open
Abstract
Tuberculosis (TB) remains a major health issue worldwide. In order to contain TB infections, improved vaccines as well as accurate and reliable diagnostic tools are desirable. Exosomes are employed for the diagnosis of various diseases. At present, research on exosomes in TB is still at the preliminary stage. Recent studies have described isolation and characterization of Mycobacterium tuberculosis (Mtb) derived exosomes in vivo and in vitro. Mtb-derived exosomes (Mtbexo) may be critical for TB pathogenesis by delivering mycobacterial-derived components to the recipient cells. Proteomic and transcriptomic analysis of Mtbexo have revealed a variety of proteins and miRNA, which are utilized by the TB bacteria for pathogenesis. Exosomes has been isolated in body fluids, are amenable for fast detection, and could contribute as diagnostic or prognostic biomarker to disease control. Extraction of exosomes from biological fluids is essential for the exosome research and requires careful standardization for TB. In this review, we summarized the different studies on Mtbexo molecules, including protein and miRNA and the method used to detect exosomes in biological fluids and cell culture supernatants. Thus, the detection of Mtbexo molecules in biological fluids may have a potential to expedite the diagnosis of TB infection. Moreover, the analysis of Mtbexo may generate new aspects in vaccine development.
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Affiliation(s)
- Fantahun Biadglegne
- College of Medicine and Health Sciences, Bahir Dar University, 79 Bahir Dar, Ethiopia
- Institute of Medical Microbiology and Epidemiology of Infectious Diseases, Medical Faculty, University of Leipzig, 04103 Leipzig, Germany; (B.K.); (A.C.R.)
- Institute of Clinical Immunology, Medical Faculty, University of Leipzig, 04103 Leipzig, Germany;
| | - Brigitte König
- Institute of Medical Microbiology and Epidemiology of Infectious Diseases, Medical Faculty, University of Leipzig, 04103 Leipzig, Germany; (B.K.); (A.C.R.)
| | - Arne C. Rodloff
- Institute of Medical Microbiology and Epidemiology of Infectious Diseases, Medical Faculty, University of Leipzig, 04103 Leipzig, Germany; (B.K.); (A.C.R.)
| | - Anca Dorhoi
- Friedrich-Loeffler-Institut, 17493 Greifswald-Insel Riems, Germany;
| | - Ulrich Sack
- Institute of Clinical Immunology, Medical Faculty, University of Leipzig, 04103 Leipzig, Germany;
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40
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Usefulness of circulating microRNAs miR-146a and miR-16-5p as prognostic biomarkers in community-acquired pneumonia. PLoS One 2020; 15:e0240926. [PMID: 33095833 PMCID: PMC7584179 DOI: 10.1371/journal.pone.0240926] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2020] [Accepted: 10/05/2020] [Indexed: 12/15/2022] Open
Abstract
Introduction Patients with community-acquired pneumonia (CAP) undergo a dysregulated host response that is related to mortality. MicroRNAs (miRNAs) participate in this response, but their expression pattern and their role as biomarkers in CAP have not been fully characterized. Methods A prospective observational study was performed in a cohort of 153 consecutive patients admitted to hospital with CAP. Clinical and analytical variables were collected, and the main outcome variable was 30-day mortality. Small RNA was purified from plasma of these patients obtained on the first day of admission, and miRNA expression was analyzed by RT-PCR. Univariate and multivariate analyses were carried out through the construction of a logistic regression model. The proposed model was compared with established prognostic clinical scales using ROC curve analysis. Results The mean age of the patients included was 74.7 years [SD 15.9]. Their mean PSI was 100.9 [SD 34.6] and the mean modified Charlson index was 2.9 [SD 3.0]. Both miR-146a and miR-16-5p showed statistically significant association with 30-day mortality after admission due to CAP (1.10 vs. 0.23 and 51.74 vs. 35.23, respectively), and this association remained for miR-16-5p in the multivariate analysis adjusted for age, gender and history of bronchoaspiration (OR 0.95, p = 0.021). The area-under-the-curve (AUC) of our adjusted multivariate model (AUC = 0.954 95%CI [0.91–0.99]), was better than those of prognostic scales such as PSI (AUC = 0.799 [0.69–0.91]) and CURB-65 (AUC = 0.722 [0.58–0.86]). Conclusions High levels of miR-146a-5p and miR-16-5p upon admission due to CAP are associated with lower mortality at 30 days of follow-up. Both miRNAs could be used as biomarkers of good prognosis in subjects hospitalized with CAP.
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Vicidomini G, Cascone R, Carlucci A, Fiorelli A, Di Domenico M, Santini M. Diagnostic and prognostic role of liquid biopsy in non-small cell lung cancer: evaluation of circulating biomarkers. EXPLORATION OF TARGETED ANTI-TUMOR THERAPY 2020; 1:343-354. [PMID: 36046486 PMCID: PMC9400689 DOI: 10.37349/etat.2020.00020] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Accepted: 09/16/2020] [Indexed: 11/19/2022] Open
Abstract
Lung cancer is still one of the main causes of cancer-related death, together with prostate and colorectal cancers in males and breast and colorectal cancers in females. The prognosis for non-small cell lung cancer (NSCLC) is strictly dependent on feasibility of a complete surgical resection of the tumor at diagnosis. Since surgery is indicated only in early stages tumors, it is necessary to anticipate the timing of diagnosis in clinical practice. In the diagnostic and therapeutic pathway for NSCLC, sampling of neoplastic tissue is usually obtained using invasive methods that are not free from disadvantages and complications. A valid alternative to the standard biopsy is the liquid biopsy (LB), that is, the analysis of samples from peripheral blood, urine, and other biological fluids, with a simple and non-invasive collection. In particular, it is possible to detect in the blood different tumor derivatives, such as cell-free DNA (cfDNA) with its subtype circulating tumor DNA (ctDNA), cell-free RNA (cfRNA), and circulating tumor cells (CTCs). Plasma-based testing seems to have several advantages over tumor tissue biopsy; firstly, it reduces medical costs, risk of complications related to invasive procedures, and turnaround times; moreover, the analysis of genes alteration, such as EGFR, ALK, ROS1, and BRAF is faster and safer with this method, compared to tissue biopsy. Despite all these advantages, the evidences in literatures indicate that assays performed on liquid biopsies have a low sensitivity, making them unsuitable for screening in lung cancer at the current state. This is caused by lack of standardization in sampling and preparation of specimen and by the low concentration of biomarkers in the bloodstream. Instead, routinely use of LB should be preferred in revaluation of patients with advanced NSCLC resistant to chemotherapy, due to onset of new mutations.
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Affiliation(s)
- Giovanni Vicidomini
- Department of Translation Medicine, Thoracic Surgery Unit, University of Campania “Luigi Vanvitelli”, 80131 Naples, Italy
| | - Roberto Cascone
- Department of Translation Medicine, Thoracic Surgery Unit, University of Campania “Luigi Vanvitelli”, 80131 Naples, Italy
| | - Annalisa Carlucci
- Department of Translation Medicine, Thoracic Surgery Unit, University of Campania “Luigi Vanvitelli”, 80131 Naples, Italy
| | - Alfonso Fiorelli
- Department of Translation Medicine, Thoracic Surgery Unit, University of Campania “Luigi Vanvitelli”, 80131 Naples, Italy
| | - Marina Di Domenico
- Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80131 Naples, Italy
| | - Mario Santini
- Department of Translation Medicine, Thoracic Surgery Unit, University of Campania “Luigi Vanvitelli”, 80131 Naples, Italy
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42
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Baburaj G, Damerla RR, Udupa KS, Parida P, Munisamy M, Kolesar J, Rao M. Liquid biopsy approaches for pleural effusion in lung cancer patients. Mol Biol Rep 2020; 47:8179-8187. [PMID: 33029702 DOI: 10.1007/s11033-020-05869-7] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2020] [Accepted: 09/25/2020] [Indexed: 12/11/2022]
Abstract
Genomic profiling of tumors has become the mainstay for diagnosis, treatment monitoring and a guide to precision medicine. However, in clinical practice, the detection of driver mutations in tumors has several procedural limitations owing to progressive disease and tumor heterogeneity. The current era of liquid biopsy promises a better solution. This diagnostic utility of liquid biopsy has been demonstrated by numerous studies for the detection of cell-free DNA (cfDNA) in plasma for disease diagnosis, prognosis, and prediction. However, cfDNAs are limited in blood circulation and still hurdles to achieve promising precision medicine. Malignant pleural effusion (MPE) is usually detected in advanced lung malignancy, which is rich in tumor cells. Extracellular vesicles and cfDNAs are the two major targets currently explored using MPE. Therefore, MPE can be used as a source of biomarkers in liquid biopsy for investigating tumor mutations. This review focuses on the liquid biopsy approaches for pleural effusion which may be explored as an alternative source for liquid biopsy in lung cancer patients to diagnose early disease progression.
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Affiliation(s)
- Gayathri Baburaj
- Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India
| | - Rama Rao Damerla
- Department of Medical Genetics, Kasturba Medical College- Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India
| | - Karthik S Udupa
- Department of Medical Oncology, Kasturba Medical College- Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India
| | - Preetiparna Parida
- Department of Medical Genetics, Kasturba Medical College- Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India
| | - Murali Munisamy
- Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India
| | - Jill Kolesar
- Department of Pharmacy Practice & Science, University of Kentucky, 567 TODD Building, 789 South Limestone Street, Lexington, KY, 40539-0596, USA
| | - Mahadev Rao
- Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India.
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43
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Hermann S, Brandes F, Kirchner B, Buschmann D, Borrmann M, Klein M, Kotschote S, Bonin M, Reithmair M, Kaufmann I, Schelling G, Pfaffl MW. Diagnostic potential of circulating cell-free microRNAs for community-acquired pneumonia and pneumonia-related sepsis. J Cell Mol Med 2020; 24:12054-12064. [PMID: 32916773 PMCID: PMC7578906 DOI: 10.1111/jcmm.15837] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Revised: 08/11/2020] [Accepted: 08/17/2020] [Indexed: 02/07/2023] Open
Abstract
Cell-free microRNAs (miRNAs) are transferred in disease state including inflammatory lung diseases and are often packed into extracellular vesicles (EVs). To assess their suitability as biomarkers for community-acquired pneumonia (CAP) and severe secondary complications such as sepsis, we studied patients with CAP (n = 30), sepsis (n = 65) and healthy volunteers (n = 47) subdivided into a training (n = 67) and a validation (n = 75) cohort. After precipitating crude EVs from sera, associated small RNA was profiled by next-generation sequencing (NGS) and evaluated in multivariate analyses. A subset of the thereby identified biomarker candidates was validated both technically and additionally by reverse transcription quantitative real-time PCR (RT-qPCR). Differential gene expression (DGE) analysis revealed 29 differentially expressed miRNAs in CAP patients when compared to volunteers, and 25 miRNAs in patients with CAP, compared to those with sepsis. Sparse partial-least discriminant analysis separated groups based on 12 miRNAs. Three miRNAs proved as a significant biomarker signature. While expression levels of miR-1246 showed significant changes with an increase in overall disease severity from volunteers to CAP and to sepsis, miR-193a-5p and miR-542-3p differentiated patients with an infectious disease (CAP or sepsis) from volunteers. Cell-free miRNAs are potentially novel biomarkers for CAP and may help to identify patients at risk for progress to sepsis, facilitating early intervention and treatment.
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Affiliation(s)
- Stefanie Hermann
- Division of Animal Physiology and Immunology, School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany
| | - Florian Brandes
- Department of Anesthesiology, University Hospital, Ludwig-Maximilians-University Munich, Munich, Germany
| | - Benedikt Kirchner
- Division of Animal Physiology and Immunology, School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany
| | - Dominik Buschmann
- Division of Animal Physiology and Immunology, School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany
| | - Melanie Borrmann
- Department of Anesthesiology, University Hospital, Ludwig-Maximilians-University Munich, Munich, Germany
| | - Matthias Klein
- Department of Neurology, University Hospital, Ludwig-Maximilians-University of Munich, Munich, Germany
| | | | | | - Marlene Reithmair
- Institute of Human Genetics, University Hospital, Ludwig-Maximilians-University Munich, Munich, Germany
| | - Ines Kaufmann
- Department of Anesthesia, Klinikum Neuperlach, Munich City Hospitals, Munich, Germany
| | - Gustav Schelling
- Department of Anesthesiology, University Hospital, Ludwig-Maximilians-University Munich, Munich, Germany
| | - Michael W Pfaffl
- Division of Animal Physiology and Immunology, School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany
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44
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Guo L, Wang Q, Zhang D. MicroRNA-4485 ameliorates severe influenza pneumonia via inhibition of the STAT3/PI3K/AKT signaling pathway. Oncol Lett 2020; 20:215. [PMID: 32963621 PMCID: PMC7491079 DOI: 10.3892/ol.2020.12078] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Accepted: 07/13/2020] [Indexed: 02/06/2023] Open
Abstract
The present study aimed to explore the potential roles and mechanism of microRNA-4485 (miR-4485) in severe influenza pneumonia. miR-4485 expression was detected in patients with severe H1N1 pneumonia using quantitative PCR. Furthermore, the effects of aberrantly expressed miR-4485 on H1N1-infected A549 cells were investigated using Cell Counting Kit-8, terminal deoxynucleotidyl transferase dUTP nick end labeling, western blotting and (ELISA) assays. Furthermore, the regulatory relationships between miR-4485 and the STAT3-mediated PI3K/AKT/mTOR signaling pathway were explored using a luciferase reporter and rescue assay. MiR-4485 expression was downregulated following H1N1 infection and in patients with H1N1 pneumonia. In addition, miR-4485 alleviated H1N1-induced A549 cell injury by promoting cell viability and the production of cytokines, as well as reducing apoptosis in A549 cells. Furthermore, STAT3 was revealed to be a target gene of miR-4485. Additionally, STAT3 silencing reversed the protective effects of miR-4485 knockdown on H1N1-induced cell injury via inhibition of the PI3K/AKT/mTOR signaling pathway. In conclusion, miR-4485 inhibited H1N1-induced severe pneumonia in A549 cells by targeting STAT3 via the PI3K/AKT/mTOR signaling pathway.
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Affiliation(s)
- Longfei Guo
- Department of Critical Care Medicine, Gansu Provincial People's Hospital, Lanzhou, Gansu 730000, P.R. China
| | - Quanhong Wang
- Department of Critical Care Medicine, Gansu Provincial People's Hospital, Lanzhou, Gansu 730000, P.R. China
| | - Dongquan Zhang
- Department of Critical Care Medicine, Gansu Provincial People's Hospital, Lanzhou, Gansu 730000, P.R. China
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45
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Critical Roles of Tumor Extracellular Vesicles in the Microenvironment of Thoracic Cancers. Int J Mol Sci 2020; 21:ijms21176024. [PMID: 32825667 PMCID: PMC7504491 DOI: 10.3390/ijms21176024] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Revised: 08/18/2020] [Accepted: 08/19/2020] [Indexed: 12/17/2022] Open
Abstract
Extracellular vesicles (EVs), such as exosomes, are critical mediators of intercellular communication between tumor cells and other cells located in the microenvironment but also in more distant sites. Exosomes are small EVs that can carry a variety of molecules, such as lipids, proteins, and non-coding RNA, especially microRNAs (miRNAs). In thoracic cancers, including lung cancers and malignant pleural mesothelioma, EVs contribute to the immune-suppressive tumor microenvironment and to tumor growth and metastasis. In this review, we discuss the recent understanding of how exosomes behave in thoracic cancers and how and why they are promising liquid biomarkers for diagnosis, prognosis, and therapy, with a special focus on exosomal miRNAs.
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46
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Li Q, Huyan T, Cai S, Huang Q, Zhang M, Peng H, Zhang Y, Liu N, Zhang W. The role of exosomal miR-375-3p: A potential suppressor in bladder cancer via the Wnt/β-catenin pathway. FASEB J 2020; 34:12177-12196. [PMID: 32716585 DOI: 10.1096/fj.202000347r] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2020] [Revised: 06/09/2020] [Accepted: 06/29/2020] [Indexed: 12/24/2022]
Abstract
miR-375-3p is a significantly downregulated miRNA in bladder cancer (BC). However, its role in BC regulation is still unclear. In this study, we reported that miR-375-3p overexpression inhibited proliferation and migration and promoted apoptosis in BC cells. Frizzled-8 (FZD8) gene is identified as the direct miR-375-3p targeting gene. miR-375-3p blocks the Wnt/β-catenin pathway and downstream molecules Cyclin D1 and c-Myc by inhibiting the expression of FZD8 directly, it could increase caspase 1 and caspase 3 expression and promote T24 cell apoptosis as well. miR-375-3p also showed a significant inhibitory effect in vivo in bladder tumor-bearing nude mice, as demonstrated by the reduced tumor volume and Ki67 proliferation index in tumor tissue. Collectively, miR-375-3p is a suppressor of BC that inhibits proliferation and metastasis, and promotes apoptosis in BC cells as well as suppresses tumor growth in a T24 xenograft mouse model, which could be used as a potential therapeutic approach for BC in future.
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Affiliation(s)
- Qi Li
- Key Laboratory for Space Bioscience and Space Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, China
| | - Ting Huyan
- Key Laboratory for Space Bioscience and Space Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, China.,Institute of Flexible Electronics, Northwestern Polytechnical University, Xi'an, China
| | - Suna Cai
- Key Laboratory for Space Bioscience and Space Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, China
| | - Qiuping Huang
- Key Laboratory for Space Bioscience and Space Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, China
| | - Mengzhao Zhang
- Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Hourong Peng
- Key Laboratory for Space Bioscience and Space Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, China
| | - Yujun Zhang
- Key Laboratory for Space Bioscience and Space Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, China
| | - Ningjing Liu
- Key Laboratory for Space Bioscience and Space Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, China
| | - Wei Zhang
- Department of Anesthesiology, Henan Provincial People's Hospital (People's Hospital of Zhengzhou University), Zhengzhou, China
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47
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Mohan A, Agarwal S, Clauss M, Britt NS, Dhillon NK. Extracellular vesicles: novel communicators in lung diseases. Respir Res 2020; 21:175. [PMID: 32641036 PMCID: PMC7341477 DOI: 10.1186/s12931-020-01423-y] [Citation(s) in RCA: 98] [Impact Index Per Article: 19.6] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2019] [Accepted: 06/15/2020] [Indexed: 02/06/2023] Open
Abstract
The lung is the organ with the highest vascular density in the human body. It is therefore perceivable that the endothelium of the lung contributes significantly to the circulation of extracellular vesicles (EVs), which include exosomes, microvesicles, and apoptotic bodies. In addition to the endothelium, EVs may arise from alveolar macrophages, fibroblasts and epithelial cells. Because EVs harbor cargo molecules, such as miRNA, mRNA, and proteins, these intercellular communicators provide important insight into the health and disease condition of donor cells and may serve as useful biomarkers of lung disease processes. This comprehensive review focuses on what is currently known about the role of EVs as markers and mediators of lung pathologies including COPD, pulmonary hypertension, asthma, lung cancer and ALI/ARDS. We also explore the role EVs can potentially serve as therapeutics for these lung diseases when released from healthy progenitor cells, such as mesenchymal stem cells.
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Affiliation(s)
- Aradhana Mohan
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Kansas Medical Center, Mail Stop 3007, 3901 Rainbow Blvd, Kansas City, KS, 66160, USA
| | - Stuti Agarwal
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Kansas Medical Center, Mail Stop 3007, 3901 Rainbow Blvd, Kansas City, KS, 66160, USA
| | - Matthias Clauss
- Division of Pulmonary, Critical Care, Sleep & Occupational Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Nicholas S Britt
- Department of Pharmacy Practice, University of Kansas School of Pharmacy, Lawrence, Kansas, USA.,Division of Infectious Diseases, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA
| | - Navneet K Dhillon
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Kansas Medical Center, Mail Stop 3007, 3901 Rainbow Blvd, Kansas City, KS, 66160, USA. .,Department of Molecular & Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas, USA.
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48
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Hu C, Meiners S, Lukas C, Stathopoulos GT, Chen J. Role of exosomal microRNAs in lung cancer biology and clinical applications. Cell Prolif 2020; 53:e12828. [PMID: 32391938 PMCID: PMC7309943 DOI: 10.1111/cpr.12828] [Citation(s) in RCA: 67] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2020] [Revised: 04/02/2020] [Accepted: 04/22/2020] [Indexed: 02/06/2023] Open
Abstract
Exosomes, small extracellular vesicles ranging from 30 to 150 nm, are secreted by various cell types, including tumour cells. Recently, microRNAs (miRNAs) were identified to be encapsulated and hence protected from degradation within exosomes. These exosomal miRNAs can be horizontally transferred to target cells, in which they subsequently modulate biological processes. Increasing evidence indicates that exosomal miRNAs play a critical role in modifying the microenvironment of lung cancers, possibly facilitating progression, invasion, angiogenesis, metastasis and drug resistance. In this review, we summarize the novel findings on exosomal miRNA functions during lung cancer initiation and progression. In addition, we highlight their potential role and challenges as biomarkers in lung cancer diagnosis, prognosis and drug resistance and as therapeutic agents.
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Affiliation(s)
- Chengping Hu
- Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, China
| | - Silke Meiners
- Comprehensive Pneumology Center and Institute for Lung Biology and Disease, University Hospital, Ludwig-Maximilians University of Munich, Munich, Germany.,Helmholtz Center Munich, Munich, Germany
| | - Christina Lukas
- Comprehensive Pneumology Center and Institute for Lung Biology and Disease, University Hospital, Ludwig-Maximilians University of Munich, Munich, Germany.,Helmholtz Center Munich, Munich, Germany
| | - Georgios T Stathopoulos
- Comprehensive Pneumology Center and Institute for Lung Biology and Disease, University Hospital, Ludwig-Maximilians University of Munich, Munich, Germany.,Helmholtz Center Munich, Munich, Germany.,Laboratory for Molecular Respiratory Carcinogenesis, Department of Physiology, Faculty of Medicine, Biomedical Sciences Research Center, University of Patras, Rio, Greece
| | - Jie Chen
- Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, China
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49
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Liu R, Zhang L, Xu Z, Cui Y. [MiR-665 Promotes the Biological Behavior of Small Cell Lung Cancer by Targeting LLGL1]. ZHONGGUO FEI AI ZA ZHI = CHINESE JOURNAL OF LUNG CANCER 2020; 23:223-232. [PMID: 32222154 PMCID: PMC7210082 DOI: 10.3779/j.issn.1009-3419.2020.104.03] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
背景与目的 MicroRNAs（miRNAs）是一种广泛存在于真核生物体中的非编码小分子RNA，尽管一些miRNA在肿瘤中作用已被发现，但是miR-665对小细胞肺癌的中的表达及影响还尚不清楚。本研究旨在分析miR-665对肺癌细胞增殖、周期、侵袭和迁移的影响，探讨miR-665在小细胞肺癌中发挥的作用及其工作机制。 方法 qRT-PCR检测miR-665在肺癌组织和癌旁正常组织中的表达水平；TargetScan预测miR-665的潜在靶基因并用双荧光素酶报告基因实验、qRT-PCR和Western blot进行验证；免疫组化、qRT-PCR和Western blot检测LLGL1在肺癌组织和癌旁正常组织中的表达水平；CCK8法、流式细胞法、Transwell和细胞划痕实验检测miR-665和LLGL1对肺癌细胞NCI-H446、NCI-H1688增殖、侵袭、迁移以及S期细胞比值的影响；构建肺癌裸鼠移植瘤模型并观察miR-665对小鼠肿瘤生长的影响。 结果 miR-665在肺癌组织中的表达水平明显高于癌旁正常组织；miR-665能靶向作用于LLGL1的3’-UTR并抑制其表达；相比于癌旁正常组织，LLGL1在肺癌组织中的表达水平明显降低；抑制miR-665的表达可以抑制肺癌NCI-H446细胞的增殖、S期细胞比值、侵袭和迁移能力，而干扰LLGL1能逆转这种抑制效果；上调miR-665则促进肺癌NCI-H1688的增殖、S期细胞比值、侵袭和迁移能力，但这种促进效果同样被LLGL1的过表达逆转；在肺癌裸鼠移植瘤模型中，抑制miR-665能上调LLGL1蛋白的表达并抑制肿瘤的生长，而上调miR-665的表达则可以产生相反的结果。 结论 miR-665表达水平的变化与肺癌密切相关，miR-665可以通过抑制其靶基因LLGL1的表达促进肺癌细胞的生物学行为，在小细胞肺癌中发挥促癌基因的作用。
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Affiliation(s)
- Rongfeng Liu
- Department of Medical Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China
| | - Lingling Zhang
- Department of Medical Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China
| | - Zhihong Xu
- Department of Medical Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China
| | - Yanzhi Cui
- Department of Medical Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China
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50
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Chen L, Cao P, Huang C, Wu Q, Chen S, Chen F. Serum exosomal miR-7977 as a novel biomarker for lung adenocarcinoma. J Cell Biochem 2020; 121:3382-3391. [PMID: 31898829 DOI: 10.1002/jcb.29612] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2019] [Accepted: 12/09/2019] [Indexed: 12/20/2022]
Abstract
Exosomal microRNAs (miRNAs) have great potentials as a novel biomarker to predict lung cancer. We applied a miRNA microarray to identify aberrantly expressed serum exosomal miRNAs as candidate biomarkers for patients with lung adenocarcinoma (LUAD). Compared with the normal control, 31 exosomal miRNAs were found to be upregulated and 29 exosomal miRNAs were downregulated in the serum of LUAD respectively. Then, 10 dysregulated exosomal miRNAs expression levels in serum were further validated via qRT-polymerase chain reaction. Notably, exosomal miR-7977 was highest expressed and miR-98-3p was lowest expressed in the patients with LUAD, and exosomal miR-7977 showed significant correlation with the N stage and TNM stage with patients with LUAD (P < .05). Receiver operating characteristic curve showed that the abundant level of exosomal miR-7977 may predict LUAD with an area of under the curve (AUC) of 0.787. In comparison with exosomal miR-7977, exosomal miR-98-3p had a smaller area (0.719). The combination of exosomal miR-7977 and miR-98-3p improved the AUC to 0.816. Furthermore, in vitro experiments revealed that inhibition of miR-7977 enhanced the proliferation, invasion, and inhibited apoptosis in A549 cells, the opposite results were performed by miR-7977 mimics. In conclusion, exosomal miR-7977 was identified as a novel biomarker for patients with LUAD and may play as a tumor suppressor in lung cancer.
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Affiliation(s)
- Liangyuan Chen
- Department of Clinical Laboratory, Fujian Provincial Hospital, Fuzhou, China.,Department of Clinical Laboratory, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
| | - Pengju Cao
- Department of Clinical Laboratory, Fujian Provincial Hospital, Fuzhou, China.,Department of Clinical Laboratory, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
| | - Chunli Huang
- Department of Clinical Laboratory, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
| | - Qiumei Wu
- Department of Clinical Laboratory, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
| | - Shaoting Chen
- Department of Clinical Laboratory, Fujian Provincial Hospital, Fuzhou, China.,Department of Clinical Laboratory, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
| | - Falin Chen
- Department of Clinical Laboratory, Fujian Provincial Hospital, Fuzhou, China.,Department of Clinical Laboratory, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
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