bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of N-adhesin and focal adhesion kinase with frequency of tumor spread through the airspace (STAS) in stage I lung carcinoma and correlation with recurrence.
Authors: Liu Hongbing , Meng Yunchang 
Published: June 2024

e20020 Background: Spread through air spaces (STAS) is one of the many modes of lung cancer dissemination. Aberrant activation of epithelial-mesenchymal transition (EMT) has been associated with enhanced tumor cell migration and invasiveness, a process that is accompanied by a decrease in adhesion molecules that maintain contact between epithelial cells, leading to cell separation and increased cell motility. Our objectives were to investigate the effect of adhesion molecule expression levels on STAS occurrence and postoperative recurrence in patients undergoing radical resection for stage I lung carcinoma. Methods: We examined the association of adhesion molecules with STAS as the primary endpoint and the Disease-Free Survival (DFS) as a secondary endpoint. E-cadherin, P-cadherin, N-cadherin, focal adhesion kinase (FAK), epithelial cell adhesion molecule (EpCAM) neural cell adhesion molecule 1 (NCAM1), vascular cell adhesion molecule 1 (VCAM1), intercellular cell adhesion molecule-1 (ICAM-1) were analyzed by immunohistochemistry in patients undergoing radical resection for stage I lung carcinoma. Associations between those adhesion molecules expression levels and STAS were determined by using the chi-square test and logistic regression model. DFS was analyzed by using the log-rank test and Cox proportional risk model. Results: As of January 1, 2024, 12 of 60 patients undergoing radical resection for stage I lung carcinoma had a disease recurrence. All of 60 patients’ tissue specimens were retrospectively analyzed, and there were no significant differences between patients with STAS-positive(n=30) and STAS-negative(n=30) in baseline clinicopathologic features, except for histological growth patterns, and lymphovascular invasion.Higher incidence of STAS was significantly associated with low expression of E-cadherin (P=0.002), high expression of N-cadherin (P=0.018) and FAK (P=0.027), and males (P=0.026), independent of tumor size, age, and clinical stage. Multivariate analysis showed that STAS (P=0.025), low E-cadherin/high N-cadherin (P=0.038), low E-cadherin/high FAK (P=0.025), and high N-cadherin/FAK (P=0.003) were significantly correlated with a higher risk of recurrence. In addition, females (P=0.034), and high N-cadherin/FAK (P=0.032) were associated with a high risk of recurrence in patients with STAS. Conclusions: Low expression of e-cadherin, high expression of N-cadherin and FAK were independent predictors of higher incidence of STAS. Tumors with low E-cadherin/high N-cadherin, low E-cadherin/high FAK, and high N-cadherin/FAK expression were important predictors of recurrence in patients with stage I lung carcinoma. Additionally, high N-cadherin/FAK expression in tumors provides information about a higher risk of recurrence in STAS-positive stage I lung carcinoma.
Comparative genomic analysis of circulating tumor cells and primary tissues in early-stage lung cancer: Unveiling signatures of metastatic potential.
Authors: Lee Jinsu , Sung Hyejin , Park Jeemin , Ji Soojeong , Kim WooJung , Jung Sojin , Cho Sukki 
Published: June 2024

e20021 Background: Recent studies substantiate the circulating tumor cells (CTCs) as biological markers for the cancer progression and metastasis. Nevertheless, isolating CTCs is challenging due to their relatively low abundance in the bloodstream. The innovative CTC detection and characterization method, iDXGate TO by BeyondDx, has overcome these challenges, facilitating the seamless identification of genomic alterations, deepening understanding of the functions of CTCs in cancer progression. Methods: In this study, a total of 50 patients diagnosed with early-stage lung cancer, without a history of anticancer therapy at Seoul National University Bundang Hospital from August 2023 to December 2023 participated to compare the genomic alterations between primary cancer tissue and CTCs. Resected tumor tissues and whole blood were collected during surgery, and DNA was freshly extracted and transferred. iDXGate TO, designed specifically for early-stage lung cancer, employs EpCAM, EGFR, and HER2 Biomarkers for targeted capture of circulating tumor cells (CTCs). Targeted sequencing was performed on the genomic DNA extracted from both cancer tissues and CTCs of each patient. Out of the CTC samples, 16 were excluded due to insufficient DNA. Results: Detailed analysis involved sequencing data from 34 CTC samples and 50 tissue samples. CTCs exhibited 100% (34/34) likely pathogenic alterations, compared to 42.00% (21/50) in tissues. Predominant genomic alterations in CTCs included MSH6 (100.0%), FANCE (91.2%), CDK12 (85.3%), HNF1A (85.3%), AXIN2 (82.4%), and FLCN (79.4%). Tissues were frequently associated with EGFR (40.0%), TP53 (34.0%), FAT1 (18.0%), LRP1B (16.0%), NOTCH3 (16.0%), and KMT2D (16.0%). Alterations in MSH6, FANCE, and CDK12 underscore the critical role of DNA repair mechanisms in CTCs, contributing to genomic instability. Alterations in HNF1A suggest implications in metabolic regulation, influencing the tumor microenvironment. Alterations in AXIN2 and FLCN hint at involvement in Wnt signaling and cellular growth regulation, potentially contributing to tumorigenesis. Conclusions: The iDXGate TO selectively identifies tumor-specific circulating tumor cells (CTCs) and explores a new realm of liquid biopsy through molecular and phenotypic integrated analysis. Detection of altered genes in CTCs highlights the molecular heterogeneity. Further exploration of these genetic alterations could offer valuable insights into the underlying mechanisms propelling cancer progression. Additionally, CTCs could serve as pivotal biomarkers for real-time monitoring of tumor evolution, potentially guiding the development of targeted therapies tailored to the specific genomic landscape of CTCs.
Comprehensive genomic and transcriptomic profiling of pulmonary nodules in synchronous multiple primary lung cancer.
Authors: Liu Xingsheng , Zhang Yi , Han Li , Li Zhenzhen 
Published: June 2024

e20022 Background: Synchronous Multiple Primary Lung Cancer (sMPLC) exhibits distinct histopathological characteristics among pulmonary nodules. However, a comprehensive understanding of the somatic mutation landscape and transcriptome heterogeneity is lacking. Therefore, our study aims to meticulously investigate genomic distinctions among multiple pulmonary nodules within individual patients. Methods: We performed targeted sequencing on tumor specimens and conducted bulk RNA transcriptome analysis on 53 multiple nodules originating from 26 lung cancer patients. The multiple nodules from the same patient was determined as major nodule and minor nodule. Additionally, the tumor tissues underwent histopathological evaluation through H&E staining, complemented by a comprehensive series of immunohistochemistry (IHC) analyses to detect protein expression. The detected protein markers encompassed PD-L1, Ki67, and others. Results: For the 53 nodule samples from 26 MPLCs patients, EGFR was the mostly mutated genes, and the TP53 mutation frequency demonstrated notably different between major and minor nodules. Furthermore, pathway enrichment analysis based on the differentially expressed genes (DEGs) between major and minor nodules revealed the significantly active cell cycle and p53 pathways in the major nodules. Additionally, both major and minor nodules demonstrated mostly similar immune microenvironment and PD-L1 protein expression, and a significantly higher expression of Ki67. A noteworthy suppression was observed in the immune microenvironment in nodules, revealed by the expression of macrophage, neutrophils, and NK cells. Furthermore, minor nodules exhibited a modestly elevated expression of macrophages compared to major nodules. Additionally, among the significantly up-regulated cell cycle related genes in the major nodules when compared with minor nodules, CCNE1 mRNA expression demonstrated significant correlation with poor prognosis in the lung cancer. Conclusions: This study validated molecular distinctions between samples from major and minor nodules in patients with sMPLC at both genomic and transcriptomic levels. The major nodules exhibited heightened activity in tumor cell proliferation pathways and demonstrated malignancy-related biological characteristics, which correlated with pathological assessment results.
Accurate identification of lung cancer in the early phase by serum exosomal miR-1271-5p.
Authors: Zhang Jinmin , Wang Lian , Zhang Haijun 
Published: June 2024

e20029 Background: Exosomal miRNAs are associated with the proliferation, migration, and invasion of lung cancer cells. We aim to investigate the clinical significance of serum exosomal miR-1271-5p in early-stage lung cancer (ESLC) mainly characterized by pulmonary nodules to push forward the prevention and treatment of lung cancer. Methods: The serum exosome (sEVs) miR-1271-5p was obtained from a total of 134 subjects from the patients with ESLC and the benign nodule (BLN) and healthy controls, and the expression level of miR-1271-5p were detected by RT-qPCR. Through analysis the clinical feature and CT (Computed Tomography) imaging finding of the subjects confirmed by pathology, independent risk factors for ESLC were obtained according to univariate and multivariate logistic regression analysis. R software was incorporated to build a mathematical prediction model of nomogram, and the clinical significance of sEVs-miR-1271-5p in the prediction and diagnosis of ESLC was verified by ROC curve. Results: The relative expression of sEVs-miR-1271-5p was lower in the patients with ESLC than the patients with BLN and healthy controls. The AUC value of the ESLC predicted by sEVs-miR-1271-5p was 0.9845 (95%CI: 0.9649-1.000, P < 0.0001). The results of multi-factor logistic regression analysis showed that gender (OR = 0.213, p = 0.046), nodule diameter (OR = 0.794, p = 0.031), lobulation (OR = 0.013, p < 0.0001), and sEVs-miR-1271-5p (OR = 0.014, p = 0.037) were independent risk factors for ESLC. Based on these independent risk factors, a prediction model for ESLC was established, with an AUC value of 0.8810 (95% CI: 0.8076-0.9553, P < 0.0001), the sensitivity, specificity, positive and negative predictive value and accuracy of the model were 85%, 80.43%, 79.07%, 86.05% and 82.56% respectively. Conclusions: Serum exosomal miR-1271-5p may break through the early diagnosis of lung cancer and provide important therapeutic targets.
Optimization of fusion detection in non-small cell lung cancer by amplicon-based RNA sequencing.
Authors: Feng Qin , Wang Yue , Lin Dongmei , Zhang Junling , Huang Mengli , Zhang Ding , Zheng Yating , Huang Depei , Ma Jing , Xiong Lei 
Published: June 2024

e20042 Background: In non-small cell lung cancer (NSCLC), more and more driver fusions are suitable for targeted therapy. Sequential or parallel DNA and RNA sequencing is an option, but it is costly and requires sufficiently high quality biopsy material. The purpose of this study was to confirm the consistency of fusion genes detected by DNA-based NGS and RNA-based NGS in the same sample, and to validate the performance of FFPE samples for RNA-based NGS. Methods: In this study, we evaluated the benefits of capture-based DNA sequencing and amplicon-based RNA sequencing in identifying gene fusion and exon-skipping events in 98 NSCLC patients. All cases were FFPE samples stored for 1-5 years. In addition, we investigated the limiting performance of RNA-based NGS for RNA initiation. Results: In the cases of positive DNA sequencing fusion samples, the fusion consistency detection rate of RNA sequencing was 95% (38/40). Two cases were not detected by RNA-based NGS, one was a five-year FFPE sample and the other was due to a probe not covered problem. In patients with negative DNA fusion genes, RNA sequencing could detect 12.07% more fusion-positive cases involving ALK (n = 1), ROS (n = 3), MET 14 exon skipping (n = 1), RET (n = 1), and BRAF (n = 1). Moreover, the FFPE samples stored for 3-5 years inevitably degrade the RNA, but could still be used for RNA-based sequencing. Among 66 FFPE samples stored for 3-5 years, the detection rate of fusion consistency between DNA sequencing fusion samples and RNA sequencing was 96.77%(30/31). In patients with negative DNA fusion genes, RNA sequencing was able to detect 14.29% (5/35) more fusion-positive cases. The performance verification of the other 8 samples with different RNA input amounts found that 87.5% (7/8) of the samples could meet the quality control of RNA sequencing and accurately detect fusion mutations as low as 1 ng. Conclusions: Molecular profiling based on mixed DNA and RNA sequencing improves the effectiveness of detection of fusion-driven NSCLC. The method was feasible on small tissue samples as well as FFPE samples stored for 3-5 years, and could greatly reduce the complexity and cost of molecular examination.
Histopathological features of SMARCA4-deficient thoracic malignancies: Data from resource-limited setting.
Authors: Karapetyan Nune , Zohrabyan Davit , Khachatryan Parandzem , Safaryan Liana , Harutyunyan Lilit , Avagyan Armen , Galumyan Aramayis , Voskanyan Gevorg , Geghamyan Gor , Mkhitaryan Sergo , Arustamyan Mikayel , Ghayamyan Meri , Karamyan Sona , Khachatryan Mariam , Arzumanyan Armen , Hovhannisyan Mariam , Bardakhchyan Samvel , Mkhitaryan Armen 
Published: June 2024

e20045 Background: SMARCA4 deficient tumors are rare malignancies that develop due to inactivating mutation in switch/sucrose-nonfermenting chromatin remodeling complexes (SWI/SNF). This is an aggressive type of non-small cell lung cancer (NSCLC) with a poor prognosis and mediocre treatment response. The trials and observational research on SMARCA4 deficient thoracic malignancies are lacking, especially in limited resource settings. This study aims to analyze pathological and immunohistochemical (IHC) profiles of patients with SMARCA4 deficient thoracic malignancies in Armenia. Methods: The current research utilizes a retrospective cohort single-center study design. The study setting was the only pathology center in Armenia that runs an IHC panel for SMARCA4/BRG1 protein evaluation. For data collection purposes, a census sampling has been done and all the pathology reports of SMARCA4 deficient thoracic malignancies were reviewed. The study timeframe was from 24 February 2021 up to 11 December 2023. Descriptive statistics through portions were done to analyze the data. Results: In total, 19 patients with SMARCA4 deficient thoracic malignancies were diagnosed. The male-to-female ratio was 15:1 and the median age was 63 years (range: 50-73 years). Of those cases, 21% (n = 4) were excluded from the current analysis as histopathological examination of those tissue samples was not performed. The diagnosis was based on an IHC evaluation to obtain a second opinion. The tissue histopathological architecture was represented: 60% (n = 9) solid, 6.67% (n = 1) trabecular, and 6.67% (n = 1) papillary. Of those samples, 66.7% (n = 10) had hyperchromatic/polymorphic nuclei and 33.3% (n = 5) pleomorphic nuclei. Similarly, the evaluated sample cells have 53.3% (n = 8) eosinophilic, 13.3% (n = 2) clear, and 13.3% (n = 2) scant cytoplasm. All 19 cases were included in the descriptive analysis of the IHC profile as examinations were performed for all the subjects. The IHC profile of the cohort is presented in the table. Ki67 was checked in 47.4% (n = 9) of cases with 70-75% median expression. In general, the most frequently examined markers were TTF1, p40, Chromogranin, and AE1/3. Conclusions: In conclusion, the study shed light on SMARCA4 thoracic tumors spread in Armenia. Considering the rarity of the disease, further research is required to investigate the actual prevalence of SMARCA4 deficient thoracic tumors and treatment approaches in Armenia. [Table: see text]
Cutaneous adverse event profile of epidermal growth factor receptor tyrosine kinase inhibitors in patients with non-small cell lung cancer: A meta-analysis of phase 3 randomized controlled trials.
Authors: Zhou Susu , Alerasool Parissa , Kishi Noriko , Rohs Nicholas Cole 
Published: June 2024

e20049 Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the frontline treatment of choice for patients with EGFR-mutant non-small cell lung cancer (NSCLC). However, EGFR-TKIs are associated with unique and dramatic dermatologic side effects that negatively impact patients’ quality of life, potentially resulting in poor adherence, including dose reductions or premature treatment cessation. Thus, it is crucial for the oncologists to be familiar with the array of dermatologic manifestations caused by these drugs for effective patient management. Methods: We performed a systematic search of PubMed, Embase, Web of Science, and Cochrane library for phase 3 randomized controlled trials (RCTs) comparing EGFR-TKI monotherapy with placebo or chemotherapy in patients with NSCLC. We calculated the odds ratio (OR) of all- and high-grade 10 dermatologic adverse events (dAEs). We conducted a meta-analysis using a random-effects model to compare the risk of dAEs in patients receiving EGFR-TKIs versus placebo/chemotherapy. Subgroup analysis based on control arm (placebo or chemotherapy) and individual EGFR-TKIs (afatinib, dacomitinib, erlotinib, gefitinib of osimertinib) were conducted. Results: 35 RCTs comprising 16,151 patients were included. In addition to all- and high-grade rash (all-grade: 12.21, 95% CI: 9.00-16.56; high-grade: OR 7.83, 95% CI: 5.11-12.00), EGFR-TKIs were associated with a significantly increased risk of all-grade acne (OR 12.24, 95% CI: 3.11-48.2), dermatitis acneiform (OR 8.46, 95% CI: 4.03-17.8), dry skin (OR 6.15, 95% CI: 4.02-9.40), palmar-plantar erythrodysesthesia syndrome (OR 11.14, 95% CI:3.00-41.4), paronychia (OR 31.97, 95% CI: 17.9-57.1), pruritus (OR 2.86, 95% CI: 2.17-3.77), skin exfoliation (OR 7.62, 95% CI: 2.55-22.8), and skin fissures (OR 11.59, 95% CI:4.86-27.6). The increased risk of EGFR-TKI-related dAEs was more prominent when compared with chemotherapy than placebo. In subgroup analyses of individual EGFR-TKIs, the risk of high-grade rash was significantly increased in patients treated with erlotinib or gefitinib but not in those treated with other EGFR-TKIs. Conclusions: This is the most comprehensive meta-analysis summarizing currently available evidence on cutaneous toxicity profile of EGFR-TKIs. These findings provide physicians with a better understanding for prompt recognition and management of these dAEs, to avoid unnecessary dose modifications and/or termination, and to prevent impairments in patients' quality of life.
Understanding the safety and toxicity profile of durvalumab for Black patients with lung cancer.
Authors: Gundroo Hafsa M , Chandora Kapil , Jack Deborah Anthony , Arnett Benson , Jain Sanjay R. 
Published: June 2024

e20051 Background: Constituting 12.2% of all new cancer diagnosis in 2023,Lung cancer continues to be among the most common cancers in the US. According to statistics 1 in 16 black males and1 in 20 black females are likely to develop lung cancer in their lifetime.The results of the PACIFIC trial changed the paradigm of management in non-resectable NonSmall Cell Ca and made Durvalumab the standard of care. The toxicity profile of the drug were extensively studied in the study however, only 2% (n-14) of the study population was Black. More studies are required to understand the tolerability and toxicity profile of the drug in the Black population. Methods: This is a retrospective study. Study population consisted of 55 self-identified African Americans diagnosed with stage 3 Non-small Cell Ca who received Durvalumab for consolidation therapy after chemo radiation at a large safety net hospital between 2018-2023.Their charts were reviewed to study: 1. The development of any grade- known adverse side effects of the drug. 2. The tolerability of the drug- assessed as the lack of severe toxicities resulting in discontinuation of the drug. 3. Appearance of any peculiar adverse effects not previously known. 4. Adverse side effects warranting the use of more healthcare resources, like ED visits and hospital admissions for adverse effects. The results were then compared to the results of the PACIFIC trial. Results: 52.7% (n=29) developed known adverse effects of the drug-any grade.20 % (n=11) developed severe adverse effects leading to discontinuation of therapy.32.7%(n=18) were able to tolerate completion of therapy in-spite of adverse effects. 16.3% ( n=9) required ED visits/ hospital visit due to immunotherapy adverse effects. ADRs leading to discontinuation of therapy-pneumonitis -9%, Debilitating Chest Pain-1.8%, Hyperglycemia- 1.8%, severe fatigue-1.8%, atrial fibrillation-1.8%, Autoimmune hepatitis -1.8% and Pan uveitis -1.8%. Other adverse effects are listed in the table. Conclusions: Based on our results, AA are more likely to develop any grade adverse effects than was estimated in the PACIFIC trial, however, the percentage of the AA population discontinuing therapy due to severe adverse effect was lower. While the occurrence of most common adverse effects including Pneumonitis was comparable to the PACIFIC trial, thyroid dysfunction – both hypo and hyperthyroidism was about 3 times more in the AA population. All the thyroid dysfunctions noted were G1 and G2, and did not require discontinuation of therapy. We therefore, recommend providers to be more watchful for signs and symptoms suggestive of thyroid dysfunction when treating AA patients with Durvalumab. [Table: see text]