A novel approach in the identification of microRNAs in malignant pleural effusion for lung cancer diagnosis.
Pleural effusion, an atypical accumulation of fluid in the pleural space, has been identified as a potential indicator of several diseases, including lung cancer. The presence of biomarkers in malignant pleural effusion has been a subject of investigation; however, the expression of microRNAs has received limited attention. The objective of this study is to present a narrative review of the current scientific literature regarding the presence of microRNAs in malignant pleural effusion and their association as new biomarkers in the diagnosis of lung cancer. A comprehensive search was conducted using the databases: PubMed, ScienceDirect, and EBSCO to identify all original scientific articles published through 30 April 2025. The following terms were utilized in the search: "MicroRNA AND pleural effusion AND lung cancer", "microRNA AND pleural effusion AND lung adenocarcinoma", "microRNA AND pleural effusion AND lung squamous cell carcinoma", "miRNA AND pleural effusion", miRNA AND pleural effusion AND lung cancer", "miRNA AND pleural effusion AND lung adenocarcinoma", "miRNA AND pleural effusion AND lung squamous cell carcinoma". A total of 17 studies were identified that distinguished between 106 microRNAs. These studies demonstrated the most significant overexpression and downexpression in lung cancer patients compared to patients without malignancy. However, eight of these studies distinguished between 17 microRNAs expressions and exhibited elevated area under the curve values, sensitivity, and specificity for the involvement in several hallmarks of lung cancer. The regulatory mechanisms governing microRNAs in malignant pleural effusion are intricate and involve multiple genes that play pivotal roles in several cancer mechanisms. These mechanisms encompass but are not limited to, processes such as cell growth, migration, drug resistance, proliferation, apoptosis, invasion, angiogenesis, and apoptosis.
- Research Article
16
- 10.1097/00029330-200804010-00001
- Apr 1, 2008
- Chinese Medical Journal
The development of the inflammatory processes in the pleural space may result in increased pleural vascular permeability leading to the accumulation of fluid enriched in proteins and the recruitment of cells into the pleural space.1 Although pleural effusion (PE) is common, very little information is available on the inflammatory and immune mechanisms that are involved in its development. In particular, it is unclear which cells and mediators are involved in the inflammatory processes and whether resident immunocompetent cells may orchestrate the development of an inflammatory response. Lymphocytic PEs refers to those in which lymphocytes account for more than 50% of the total leukocytes in PE. Lymphocytic effusions are commonly (>90% of cases) the result of malignancy and tuberculous pleurisy, but can also occur with rheumatic diseases, chronic postcoronary artery bypass effusion, chylothorax, acute lung allograft rejection and yellow nail syndrome.2 In normal humans a small amount of PE is present, but the exact volume of this fluid is unknown. In normal PE, there is a predominance of macrophages and lymphocytes; mesothelial cells, neutrophils and eosinophils are only marginally present.3 In an early study, it has been demonstrated that both the percentage and absolute numbers of T lymphocytes in tuberculous PE were significantly higher than in the corresponding peripheral blood. On the other hand, in patients with pulmonary tuberculosis, pulmonary malignancy or nonspecific pleurisy the percentages and absolute numbers of B lymphocytes were significantly lower in PE than in peripheral blood.4 It has been reported that PE is enriched with CD4+CDw29+ T cells, which are thought to represent “memory” T cells, and these PE CD4+CDw29+ cells, but not CD4+CDw29- cells, proliferated vigorously and produced high levels of interferon (IFN)-γ when stimulated with a purified protein derivative of Mycobacterium tuberculosis.5 Therefore, in tuberculous PE, CD4+CDw29+ cells are concentrated at the site of disease activity, produce IFN-γ and are likely to play an important role in the local human cell-mediated immune response to Mycobacterium tuberculosis. Malignant PE is frequently observed in lung cancer and a diagnosis of malignant PE with lung cancer carries a poor prognosis. In malignant PE, CD4+ T cells are dominant and the proportion of CD8+ T cells is significantly lower than that of CD4+ T cells.6 In contrast, the proportion of CD4+ T cells in the pleural cavity of patients with lung cancer without malignant PE is significantly lower than that of CD8+ T cells.7 Furthermore the proportion of PE CD4+ T cells may help to select patients who are likely to have a poorer prognosis after surgery and therefore may be suitable for consideration of adjuvant treatments.8 Immunoregulatory T cells have been believed to be involved in the control of the local immune response and in the growth of malignant tumors.9 Studies ongoing for more than a decade have provided firm evidence for the existence of a unique CD4+CD25+ T-cell population of “professional” regulatory/suppressor T cells that actively and dominantly prevent both the activation and the effector function of autoreactive T cells that have escaped other mechanisms of tolerance.10,11 Our previous study has shown that CD4+CD25+ T-cell numbers in malignant PE were much higher than those in PE from patients with lung cancer without malignant effusion and higher than numbers in peripheral blood. Our data also revealed that CD4+CD25+ T cells infiltrating PE were regulatory T cells as they express high levels of Foxp3 transcription factor. Moreover, pleural CD4+CD25+ T cells could potently suppress the proliferation of CD4+CD25- T cells and cytotoxic lymphocyte-associated antigen-4 was involved in the suppressive activity of pleural CD4+CD25+ T cells.12 In addition, we have demonstrated that CD4+CD25+ T cell numbers in tuberculous PE were much higher than those in peripheral blood from patients with tuberculous PE and from healthy subjects, and that the CD4+CD25+ T cells infiltrating pleural space were regulatory T cells as they expressed high levels of Foxp3 transcription factor. Moreover, tuberculous PE-derived CD4+CD25+ T cells could potently suppress the proliferation of responding T cells.13 It has been reported that the long-term effects of adoptively transferred CD4+CD25+ T cells induced ex vivo are due to their ability to generate new cytokine-producing CD4+CD25+ T cells in vivo.14 We speculated that an increased percentage of CD4+CD25+ T cells in PE might be due to either active recruitment or local differentiation. It has been demonstrated that human CD4+CD25+ T cells preferentially move to and accumulate in tumors and ascites, but rarely enter draining lymph nodes in later cancer stages.15 In a previous study, we provided direct evidence that interleukin (IL)-16 is capable of inducing CD4+ T-cell infiltration into the pleural space.16 Therefore, as a subpopulation of CD4+ T cells, CD4+CD25+ T cells might also be recruited into PE by local production of IL-16, because the IL-16 level is significantly higher in PE than in serum.16 Since we observed that CD4+CD25+ T cells were overrepresented in malignant and tuberculous PEs, this raised the question whether these cells could be recruited from the circulation. In a recent study, we have found that the level of chemokine CCL22 in PE correlated best with the numbers of CD4+CD25+ T cells, and that an anti-CCL22 antibody inhibited the ability of the PE to stimulate peripheral CD4+CD25+ T cell chemotaxis in vitro. Moreover, intrapleural administration of human recombinant CCL22, but not vehicle, into patients with PE produced a marked progressive influx of CD4+CD25+ T cells into the pleural space when studied by flow cytometry (our unpublished data). Our results demonstrated that CCL22 is produced by pleural cells and would appear to play a crucial role in the directed migration of CD4+CD25+ regulatory T cells into the pleural space. The role of T cells as active players in the mediation of pleural pathologies is beginning to be recognized. Understanding the exact roles of T cells in pleural space may provide a foundation for potential future attempts to augment lymphocyte responses. Further study of specific cellular responses may provide insight into disease pathogenesis and may offer unique opportunities in the diagnosis and management of lymphocytic PE. For example, since CD4+CD25+ T-cell numbers are increased in malignant PE, and these pleural CD4+CD25+ T cells can potently suppress the proliferation of CD4+CD25- T cells, it is very possible to develop novel immune-boosting strategies based on eliminating this regulatory cell population in patients with cancer. Also, more work is required to delineate the role of CD4+CD25+ T cells in tuberculous PE. Further studies should be directed at identifying the mediators and mechanisms involved in the immunoregulatory properties of pleural CD4+CD25+ T cells in patients with tuberculous PE.
- Research Article
- 10.3760/cma.j.issn.1008-6706.2018.16.003
- Aug 15, 2018
- Chinese Journal of Primary Medicine and Pharmacy
Objective To investigate the diagnostic value of cell wax block combined with immunohistochemistry in the diagnosis of malignant pleural effusion in lung adenocarcinoma and to analyze the expression and clinical significance of EGFR in pleural effusion. Methods From March 2013 to June 2017, 50 lung cancer patients with pleural effusion specimens and corresponding histological specimens of lung adenocarcinoma in the Central Hospital of Wenzhou were selected.The intensity of EGFR expression in pleural effusion lung adenocarcinoma cells was detected.The difference of EGFR expression between pleural effusion cells and paraffin blocks was compared by ARMS method. Results The EGFR negative, weak positive, moderate positive and strong positive expression rates were 1 case(2.0%), 8 cases(16.0%), 20 cases(40.0%) and 21 cases(42.0%), respectively.There were no statistically significant differences in the sensitivity and specificity between the ARMS method and the immunohistochemical staining of lung cancer tissues(χ2=0.000, 0.006, all P>0.05). The consistency of detection was excellent (Kappa value=0.93, P 0.05), and the consistency was better(Kappa value=0.72, P<0.05). Conclusion Pleural effusion cells have the advantages of easy access, low cost, simple operation and good specificity, which is an easy and effective method to assess the expression of EGFR gene mutation in lung adenocarcinoma, which provides a reference for individualized treatment and prognosis of advanced lung adenocarcinoma. Key words: Pleural effusion, malignant; Lung neoplasms; Receptor, epidermal growth factor
- Research Article
- 10.1016/j.mayocp.2020.07.045
- Mar 10, 2021
- Mayo Clinic Proceedings
48-Year-Old Woman With Dyspnea and Chest Pain
- Research Article
- 10.3760/cma.j.issn.1007-1245.2019.03.027
- Feb 1, 2019
- International Medicine and Health Guidance News
Objective To investigate the value of paraffin-embedded section of cell block in the diagnosis of benign or malignant pleural and peritoneal effusion. Methods 105 patients suspected with malignant pleural and peritoneal effusion admitted into tour hospital from November, 2015 to December, 2017 were selected as the research objects. The specimens of pleural and peritoneal effusion of all the patients were collected. And these specimens were given paraffin-embedded section of cell block, cell smear, and exfoliative cell pathological examination. The results of exfoliative cell pathological examination were taken as the gold standard. The positive rates of malignant pleural and peritoneal effusion diagnosed by paraffin-embedded section of cell block and cell smear were evaluated. The diagnostic value of the two methods was compared. Results Among the 50 pleural effusion specimens, the results of exfoliative cell pathological examination showed that there were 36 cases of malignant pleural effusion. Among the 55 peritoneal effusion specimens, the results of exfoliative cell pathological examination showed that there were 42 cases of malignant peritoneal effusion. The positive detection rate of pleural effusion diagnosed by paraffin-embedded section of cell block (80.56%) was higher than that diagnosed by cell smear (58.33%), with a statistical difference (P<0.05). The positive detection rate of peritoneal effusion diagnosed by paraffin-embedded section of cell block (85.71%) was higher than that diagnosed by cell smear (64.29%), with a statistical difference (P<0.05). The sensitivity, specificity, and accuracy of paraffin-embedded section of cell block in the diagnosis of malignant pleural and peritoneal effusion were higher than those of cell smear, with statistical differences (all P<0.05). Conclusions Paraffin-embedded section of cell block in the differential diagnosis of benign or malignant pleural and peritoneal effusion has high sensitivity and specificity, and can increase the diagnostic accuracy and provide an important basis for clinical diagnosis and treatment of the disease. Key words: Pleural effusion; Paraffin-embedded section of cell block; Cell smear; Exfoliative cell pathological examination
- Research Article
2
- 10.3779/j.issn.1009-3419.2006.03.14
- Jun 20, 2006
- Chinese journal of lung cancer
Malignant pleural effusion is usually caused by lung cancer, and tumor markers may be helpful to its differential diagnosis. The aim of this study is to explore the clinical value of serum and pleural effusion pro-gastrin-releasing peptide (ProGRP), neuron specific enolase (NSE), cyto- keratin fragment 19 (CYFRA21-1) and carcinoembryonic antigen (CEA) in differential diagnosis and histological typing of malignant pleural effusion caused by lung cancer. According to histological type of primary tumor, 99 patients with malignant pleural effusion caused by lung cancer were divided into small cell lung cancer (SCLC) group, adenocarcinoma group and squamous cell carcinoma group, with 37 patients with benign pleural effusion and 35 healthy persons as controls. Diagnostic value of serum and pleural effusion ProGRP , NSE, CYFRA21-1 and CEA was evaluated for each group. The levels of ProGRP, NSE, CYFRA21-1 and CEA in serum and pleural effusion of all the malignant groups were significantly higher than those in the control groups (P < 0.01). In the SCLC group, detection of pleural effusion ProGRP showed the highest Youden index and accuracy. In the adenocarcinoma group and squamous cell carcinoma group, combined detection of pleural effusion CEA+CYFRA21-1 (on parallel test) showed the highest Youden index and accuracy. Detection of pleural effusion tumor markers ProGRP, CYFRA21-1, NSE and CEA is of great clinical value in differential diagnosis and histological typing of malignant pleural effusion. Pleural effusion ProGRP is the optimal tumor marker for malignant pleural effusion caused by SCLC. Pleural effusion CEA+CYFRA21-1 (on parallel test) is a good auxiliary diagnosis index for malignant pleural effusion caused by adenocarcinoma and squamous cell carcinoma of the lung.
- Discussion
- 10.1016/s0003-4975(02)03943-7
- Oct 25, 2002
- The Annals of Thoracic Surgery
Reply
- Abstract
45
- 10.1016/s0169-5002(86)80047-2
- Oct 1, 1986
- Lung Cancer
Monoclonal antibodies to human squamous cell carcinoma of the lung and their application to tumor diagnosis
- Research Article
3
- 10.1111/resp.12048
- Mar 21, 2013
- Respirology
This Year in Review series addresses the most relevant articles published in Respirology and other respiratory medicine journals during 2012 concerning five specific areas that we consider to be of importance to practicing pulmonologists, namely lung cancer, respiratory infections, tuberculosis (TB), pleural diseases, and interventional pulmonology and imaging. Some important findings that will be commented on more in depth are that: 1) screening for lung cancer using low-dose computed tomography (CT) in high risk populations is promising, although not firmly established, 2) an enhanced CURB (which stands for confusion, urea, respiratory rate, blood pressure) score as well as the Japanese A-DROP (age, dehydration, respiratory failure, orientation disturbance, and pressure) prognostic scale are as accurate as the pneumonia severity index (PSI) scoring system to predict mortality in patients with community-acquired pneumonia (CAP), 3) randomized trials are urgently needed to optimize multidrug-resistant (MDR)-TB treatment, 4) the use of video-assisted thoracoscopic surgery (VATS) to quantify pleural tumor burden and, if feasible, perform an intrathoracic cytoreduction in patients with malignant effusions secondary to ovarian cancer (OC) may have a significant impact on further patient management plans, and 5) respiratory endoscopy and its different diagnostic and therapeutic modalities, is a safe procedure with overall complication rates less than 1%.
- Research Article
- 10.12122/j.issn.1673-4254.2019.06.03
- Jun 30, 2019
- Nan fang yi ke da xue xue bao = Journal of Southern Medical University
To analyze the differentially expressed genes (DEGs) between lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) with bioinformatics analysis and search for potential biomarkers for clinical diagnosis of nonsmall cell lung cancer (NSCLC). The gene expression profiling datasets of LUAD and LUSC were acquired. The transcriptome differences between LUAD and LUSC were identified using R language processing and t-test analysis. The differential expressions of the genes were shown by Venn diagram. The DEGs identified by GEO2R were analyzed with DAVID and Ingenuity Pathway Analysis (IPA) to identify the signaling pathways and biomarkers that could be used for differential diagnosis of LUAD and LUSC. The TCGA data and the biomarker expression data from clinical lung cancer samples were used to verify the differential expressions of the Osteoarthritis pathway and LXR/RXR between LUAD and LUSC. We further examined the differential expressions of miR-181 and its two target genes, WNT5A and MBD2, in 23 clinical specimens of lung squamous cell carcinoma and the paired adjacent tissues. GEO data analysis identified 851 DEGs (including 276 up-regulated and 575 down-regulated genes) in LUAD and 885 DEGs (including 406 up-regulated and 479 down-regulated genes) in LUSC. DAVID and IPA analysis revealed that leukocyte migration and inflammatory responses were more abundant in LUAD than in LUSC. Osteoarthritis pathway was inhibited in LUAD and activated in LUSC. IPA analysis showed that transcription factors (GATA4, RELA, YBX1, TP63 and MBD2), cytokines (WNT5A and IL1A) and microRNAs (miR-34a, miR-181b and miR-15a) differed significantly between LUAD and LUSC. miR-34a with IL-1A, miR-15a with YBX1, and miR-181b with WNT5A and MBD2 could serve as the paired microRNA and mRNA targets for differential diagnosis of NSCLC subtypes. Analysis of the clinical samples showed an increased expression of miR-181b-5p and the down-regulation of WNT5A, which could be used as molecular markers for the diagnosis of LUSC. Through transcriptome analysis, we identified candidate genes, paired microRNAs and pathways for differentiating LUAD and LUSC, and they can provide novel differential diagnosis and therapeutic strategies for LUAD and LUSC.
- Research Article
- 10.3760/cma.j.issn.1009-9158.2012.12.021
- Dec 11, 2012
- Chinese Journal of Laboratory Medicine
Objective To investigate the diagnostic value of detection of protein SP70 in differentiating benign and malignant pleural effusion. Methods A case-control study was conducted from July 2011 to February 2012. 108 cases of pleural effusion from patients with clinically proven lung cancers and 122 cases of benign pleural effusion were collected.SP70 was detected by Sandwich ELISA,while CEA,CYFRA21-1,NSE were measured by electrochemiluminescence immunoassay for comparison.Meanwhile,protein SP70 on exfoliated cells in pleural effusion was detected by direct immunofluorescence, and was compared with the results of HE staining.The differences between the groups were evaluated by the chi-square test Fisher′s exact test. Results Positive rates of SP70,CEA,CYFRA21-1,NSE were 72.2%,58.3%,52.8% and 30.6% in malignant pleural effusion,obviously higher than benign pleural effusio(9.8%,13.1%,23.0% and 19.7%).The specificity of SP70,CEA,CYFRA21-1,NSE were 90.2%,86.9%,77.0% and 80.3%,NSCLC had significantly higher positive rate than SCLC(74.3%>0.0%,P=0.02<0.05), detection of protein SP70 in malignant pleural effusion had significantly higher coincidence rate than HE staining(72.2% vs 47.2%, χ2 =14.03,P<0.05). Conclusion Determination of the protein SP70 in pleural effusion and in exfoliated cells,can improve the sensitivity and specificity of the diagnosis of malignant pleural effusion.(Chin J Lab Med,2012,35:1150-1154) Key words: Enzyme linked immunosorbent assay; Fluoroimmunoassay; Pleural effusion; Tumor markers,biological
- Research Article
3
- 10.1097/md.0000000000032861
- Feb 10, 2023
- Medicine
Previous studies have shown that asthma is a risk factor for lung cancer, while the mechanisms involved remain unclear. We attempted to further explore the association between asthma and non-small cell lung cancer (NSCLC) via bioinformatics analysis. We obtained GSE143303 and GSE18842 from the GEO database. Lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) groups were downloaded from the TCGA database. Based on the results of differentially expressed genes (DEGs) between asthma and NSCLC, we determined common DEGs by constructing a Venn diagram. Enrichment analysis was used to explore the common pathways of asthma and NSCLC. A protein-protein interaction (PPI) network was constructed to screen hub genes. KM survival analysis was performed to screen prognostic genes in the LUAD and LUSC groups. A Cox model was constructed based on hub genes and validated internally and externally. Tumor Immune Estimation Resource (TIMER) was used to evaluate the association of prognostic gene models with the tumor microenvironment (TME) and immune cell infiltration. Nomogram model was constructed by combining prognostic genes and clinical features. 114 common DEGs were obtained based on asthma and NSCLC data, and enrichment analysis showed that significant enrichment pathways mainly focused on inflammatory pathways. Screening of 5 hub genes as a key prognostic gene model for asthma progression to LUAD, and internal and external validation led to consistent conclusions. In addition, the risk score of the 5 hub genes could be used as a tool to assess the TME and immune cell infiltration. The nomogram model constructed by combining the 5 hub genes with clinical features was accurate for LUAD. Five-hub genes enrich our understanding of the potential mechanisms by which asthma contributes to the increased risk of lung cancer.
- Research Article
- 10.3760/cma.j.issn.1673-436x.2017.15.003
- Aug 5, 2017
- Chinese Journal of Asthma
Objective To evaluate the diagnostic value of procalcitonin (PCT) and lactate dehydrogenase (LDH) in pleural effusions for lung cancer with malignant pleural effusion. Methods The patients with pleural effusion in Jiangyin People′s Hospital from January 2015 to February 2017 were selected and divided into lung cancer group and tuberculosis group.The levels of PCT and LDH were detected and made statistical analysis. Results The levels of PCT and LDH in pleural effusion of lung cancer group were significantly higher than those of tuberculosis group (t=7.298, 5.607, all P<0.05). The combined detection of PCT and LDH could improve the accuracy of diagnosis. Conclusions The combined detection of PCT and LDH has important clinical significance in the diagnosis of lung cancer with malignant pleural effusion. Key words: Procalcitonin; Lactate dehydrogenase; Lung cancer; Pleural effusion
- Research Article
- 10.3760/cma.j.issn.1008-6315.2013.12.016
- Dec 1, 2013
Objective To investigate the change of serum cancer antigen(CA) 125 in patients with pleural effusion.Methods One hundred and twenty-eight patients with pleural effusion were admitted to the Naval General Hospital of People's Liberation Army from January 2010 to September 2012 were selected as our subjects.The level of serum CA125 was measured.The difference of serum CA125 positive rate and level were compared according to gender,pleural effusion nature,quantity and pleural effusion chest area; And the difference of patients with malignant pleural effusion tuberculosis,inflammatory,exudative pleural effusion based on above indicators.The correlation between serum CA125 level and pleural effusion depth were analyzed.Results The positive proportions of CA125 were 83.3% (35/42) and 76.7 % (66/88) of patients with malignant and benign effusion respectively,and there was no significant difference (x2 =0.74,P > 0.05).The serum CA125 level of patients with malignant pleural effusion was significantly higher than benign ones ((177.8 ± 31.4) U/ml vs.(110.6 ± 13.6) U/ml,t =31.24,P < 0.05).There were no significant difference in the positive proportion of serum CA125 between malignant,tuberculous,inflammatory and transudative pleural effusion(75.8% (25/33),70.0% (20/29),87.5% (21/24) and 83.3% (35/42),P > 0.05).Serum CA125 levels of patients with malignant pleural effusion were significantly higher than that with inflammatory ((177.8 ± 31.4) U/ml vs.(72.5 ± 12.8) U/ml,P < 0.05),but the differences were not significant among malignant,tuberculous and transudative pleural effusion group((140.6 ± 28.2) U/ml,(154.3 ± 30.5) U/ml,P > 0.05).The serum CA125 levels of patients with small,moderate and large effusions were (56.4 ± 18.2) U/ml,(120.2 ± 24.5) U/ml and (185.5 ± 34.6) U/ml respectively,and the difference among these groups were significant(F =296.03,P < 0.05).Serum CA125 levels was positively correlated with pleural fluid depth (r =0.56,P <0.01).Different gender,pleural effusion parts serum CA125 positive rate and the different levels were not statistically significant (P > 0.05).Conclusion Serum CA125 increased in patients with benign and malignant pleural effusion,and serum CA125 was not severed as the diagnosis biomarker in differentiating benign and malignant pleural effusion.Serum CA125 levels is helpful in monitoring the change of pleural fluid size due to the relation with depth of pleural fluid. Key words: Pleural effusion; Cancer antigen 125 ; Serum
- Research Article
- 10.1158/1538-7445.am2025-2106
- Apr 21, 2025
- Cancer Research
Background: Lung cancer is a leading cause of death. Despite advancements in early diagnosis and treatment, most patients are diagnosed at later stages, and the average 5-year survival rate is &lt; 30%. Lung adenocarcinoma (LUAD) is the most common non-small cell lung cancer (NSCLC), representing about 40% of cases, followed by lung squamous cell carcinoma (LUSC) at 25%. The biological patterns and molecular characteristics of LUAD and LUSC exhibit differences. Changes in DNA methylation levels of various genes have been observed in lung cancer subtypes, yet research on differences in DNA methylation patterns between LUAD and LUSC is limited. Methods: The methylation microarray dataset (GSE39279, Illumina HumanMethylation450 BeadChip) from Gene Expression Omnibus at the National Center for Biotechnology Information was used. The dataset comprised 444 NSCLC samples derived from tumor tissues, of which 322 were LUAD and 122 were LUSC. We used the Champ (Chip Analysis Methylation Pipeline) package to identify differentially methylated probes (DMPs, Benjamini-Hochberg adjusted p-value &lt; 0.05) and genes representing specific biological pathways between LUAD and LUSC. Singular Value Decomposition regression analysis was used to estimate the impact of age, sex, and smoking status and then adjusted for the covariates with p-values &lt; 0.05. We used the eFORGE TF database to calculate the Find Individual Motif Occurrences (FIMO) p-values for the overlap with transcription factor binding sites. The Gene Expression Profiling Interactive Analysis database was used to measure the gene expression levels of LUAD and LUSC samples in the Genotype-Tissue Expression and the Cancer Genome Atlas Program portals. Results: In total, 223,007 DMPs were identified by comparing LUAD and LUAC, with 130,610 hypomethylated and 92,467 hypermethylated. Using the absolute difference of β values between groups ≥ 0.3, we identified 15 DMPs, 11 hypomethylated and four hypermethylated. The DMPs on promoter regions were all hypomethylated in LUSC compared to LUAD (cg00415665 and cg22997040 in ZHX2, cg27649037 in ST18, cg20691436 in CALML3, and cg24580076 in C7orf20). We also identified DMPs based on the importance scores (&gt; 0.1) from a 5-fold cross-validation random forest analysis. The two DMPs in the ZHX2 gene had the highest importance scores (&gt; 8.0). Among those, cg00415665 was covered by the Zfp161_secondary motif (FIMO p-value: &lt; 10-5). The average expression level of ZHX2 in LUSC (transcripts per million, TPM=9.7) was higher than in LUAD (TPM=8.2). Conclusions: We characterized the methylation landscape of NSCLCs by histological subtypes and identified that the methylation pattern of cg00415665 in ZHX2, a tumor suppressor gene, was significantly associated with the histological subtype of NSCLC. Further investigation of these findings will provide additional insight into the biology and genetics of LUAD and LUSC. Citation Format: Hyeyeun Lim, Christopher I. Amos, Jinyoung Byun, Aaron P. Aaron. Comparing the methylation profiles between lung adenocarcinoma and squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2106.
- 10.26911/theijmed.2020.05.04.09
- Jan 29, 2021
Background: Pleural effusion can be an early sign of lung cancer in more than 25% of cases. Lung cancer is the most common cause of malignant pleural effusion (MPE). Pleurodesis is performed when the amount of pleural fluid is <150 ml/day, but it is difficult as its productive nature. This study aimed to find the right time to perform pleurodesis on patients with MPE, which is expected to achieve optimal results. Subjects and Method: This was a cross-sectional study conducted at Dr. Moewardi Hospital, Surakarta, Central Java, from June to July 2020. The study subjects were 17 patients with malignant pleural effusion (MPE) diagnosed with lung cancer who underwent water seal drainage (WSD) and indicated for pleurodesis. The dependent variable was the success of the pleurodesis procedure. The independent variables were the amount of evacuated pleural fluid and the time of pleurodesis performed. The study instruments were diagnosis of lung cancer with anatomic pathology, measurement of the amount of pleural fluid, and posteroanterior chest X-ray evaluating the success of pleurodesis. The data were analyzed using Spearman correlation, ANOVA to determine the differences in the amount of pleural fluid at the first, second, and third hours, and continued with post hoc LSD analysis using SPSS 21. Results: The pleurodesis success rate had positive correlation with the amount of pleural fluid (r= 0.24; p= 0.345) and the time of pleurodesis performed at the first hour (r= 0.10; p= 0.701), second hour (r= 0.03; p= 0.921), and third hour (r= 0.41; p= 0.106). Pleurodesis performed at the second hour had the lowest amount of pleural fluid (Mean= 84.66; SD= 38.88), followed by third hour (Mean= 110.77; SD= 65.57), and first hour (Mean= 111.22; SD= 57.83), but the differences were not statistically significant (p= 0.285). Conclusion: The pleurodesis success rate has a positive correlation with the amount of pleural fluid and the time of pleurodesis, but it was not statistically significant. There is no significant difference in the amount of pleural fluid evacuated at the three different times of pleurodesis. The least amount of pleural fluid obtains at the second hour (14.00-22.00). Keywords: malignant pleural effusion, amount of pleural fluid, pleurodesis, pleurodesis time Correspondence: Yusup Subagio Sutanto. Department of Pulmonology and Respiratory Medicine, Faculty of Medicine Universitas Sebelas Maret, Dr. Moewardi Hospital, Surakarta. Jl. Kolonel Sutarto 132, Surakarta 57126, Central Java. Email: dr_yusupsubagio@yahoo.com. Mobile: +62811284165. Indonesian Journal of Medicine (2020), 05(04): 337-342 https://doi.org/10.26911/theijmed.2020.05.04.09.