Purpose: We aimed to comprehensively analyze the immune cell and stromal components of tumor microenvironment at the single-cell level and identify tumor heterogeneity among the major top-derived oncogene mutations in non-small cell lung cancer (NSCLC) using single-cell RNA sequencing (scRNA-seq) data. Materials and Methods: The scRNA-seq dataset utilized in this study comprised 64369 primary tumor tissue cells from 21 NSCLC patients, focusing on mutations in EGFR, ALK, BRAF, KRAS, TP53, and the wild-type. Results: Tumor immune microenvironment (TIM) analysis revealed differential immune responses across NSCLC mutation subtypes. TIM analysis revealed different immune responses across the mutation subtypes. Two mutation clusters emerged: KRAS, TP53, and EGFR+TP53 mutations (MC1); and EGFR, BRAF, and ALK mutations (MC2). MC1 showed higher tertiary lymphoid structures signature scores and enriched populations of C2-T-IL7R, C3-T/NK-CXCL4, C9-T/NK-NKG, and C1-B-MS4A1 clusters than cluster 2. Conversely, MC2 cells exhibited higher expression levels of TNF, IL1B, and chemokines linked to alternative immune pathways. Remarkably, co-occurring EGFR and TP53 mutations were grouped as MC1. EGFR+TP53 mutations showed upregulation of peptide synthesis and higher synthetic processes, as well as differences in myeloid and T/NK cells compared to EGFR mutations. In T/NK cells, EGFR+TP53 mutations showed a higher expression of features related to cell activity and differentiation, whereas EGFR mutations showed the opposite. Conclusion Our research indicates a close association between mutation types and tumor microenvironment in NSCLC, offering insights into personalized approaches for cancer diagnosis and treatment.

Background: The role of apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) in adipose tissue remains poorly understood. This study investigates adipose tissue dysfunction in heterozygous APE1/Ref-1 deficiency (APE1/Ref-1+/-) mice, focusing on changes in adipocyte physiology, oxidative stress, adipokine regulation, and adipose tissue distribution. Methods: APE1/Ref-1 mRNA and protein levels in white adipose tissue (WAT) were measured in APE1/Ref-1+/- mice, compared to their wild-type (APE1/Ref-1+/+) controls. Oxidative stress was assessed by evaluating reactive oxygen species (ROS) levels. Histological and immunohistochemical analyses were conducted to observe adipocyte size and macrophage infiltration of WAT. Adipokine expression was measured, and micro-magnetic resonance imaging (MRI) was used to quantify abdominal fat volumes. Results: APE1/Ref-1+/- mice exhibited significant reductions in APE1/Ref-1 mRNA and protein levels in WAT and liver tissue. These mice also showed elevated ROS levels, suggesting a regulatory role for APE1/Ref-1 in oxidative stress in WAT and liver. Histological and immunohistochemical analyses revealed hypertrophic adipocytes and macrophage infiltration in WAT, while Oil Red O staining demonstrated enhanced ectopic fat deposition in the liver of APE1/Ref-1+/- mice. These mice also displayed altered adipokine expression, with decreased adiponectin and increased leptin levels in the WAT, along with corresponding alterations in plasma levels. Despite no significant changes in overall body weight, microMRI assessments demonstrated a significant increase in visceral and subcutaneous abdominal fat volumes in APE1/Ref-1+/- mice. Conclusion APE1/Ref-1 is crucial in adipokine regulation and mitigating oxidative stress. These findings suggest its involvement in adipose tissue dysfunction, highlighting its potential impact on abdominal fat distribution and its implications for obesity and oxidative stress-related conditions.

Purpose: We aimed to comprehensively analyze the immune cell and stromal components of tumor microenvironment at the single-cell level and identify tumor heterogeneity among the major top-derived oncogene mutations in non-small cell lung cancer (NSCLC) using single-cell RNA sequencing (scRNA-seq) data. Materials and Methods: The scRNA-seq dataset utilized in this study comprised 64369 primary tumor tissue cells from 21 NSCLC patients, focusing on mutations in EGFR, ALK, BRAF, KRAS, TP53, and the wild-type. Results: Tumor immune microenvironment (TIM) analysis revealed differential immune responses across NSCLC mutation subtypes. TIM analysis revealed different immune responses across the mutation subtypes. Two mutation clusters emerged: KRAS, TP53, and EGFR+TP53 mutations (MC1); and EGFR, BRAF, and ALK mutations (MC2). MC1 showed higher tertiary lymphoid structures signature scores and enriched populations of C2-T-IL7R, C3-T/NK-CXCL4, C9-T/NK-NKG, and C1-B-MS4A1 clusters than cluster 2. Conversely, MC2 cells exhibited higher expression levels of TNF, IL1B, and chemokines linked to alternative immune pathways. Remarkably, co-occurring EGFR and TP53 mutations were grouped as MC1. EGFR+TP53 mutations showed upregulation of peptide synthesis and higher synthetic processes, as well as differences in myeloid and T/NK cells compared to EGFR mutations. In T/NK cells, EGFR+TP53 mutations showed a higher expression of features related to cell activity and differentiation, whereas EGFR mutations showed the opposite. Conclusion Our research indicates a close association between mutation types and tumor microenvironment in NSCLC, offering insights into personalized approaches for cancer diagnosis and treatment.

Purpose: We aimed to comprehensively analyze the immune cell and stromal components of tumor microenvironment at the single-cell level and identify tumor heterogeneity among the major top-derived oncogene mutations in non-small cell lung cancer (NSCLC) using single-cell RNA sequencing (scRNA-seq) data. Materials and Methods: The scRNA-seq dataset utilized in this study comprised 64369 primary tumor tissue cells from 21 NSCLC patients, focusing on mutations in EGFR, ALK, BRAF, KRAS, TP53, and the wild-type. Results: Tumor immune microenvironment (TIM) analysis revealed differential immune responses across NSCLC mutation subtypes. TIM analysis revealed different immune responses across the mutation subtypes. Two mutation clusters emerged: KRAS, TP53, and EGFR+TP53 mutations (MC1); and EGFR, BRAF, and ALK mutations (MC2). MC1 showed higher tertiary lymphoid structures signature scores and enriched populations of C2-T-IL7R, C3-T/NK-CXCL4, C9-T/NK-NKG, and C1-B-MS4A1 clusters than cluster 2. Conversely, MC2 cells exhibited higher expression levels of TNF, IL1B, and chemokines linked to alternative immune pathways. Remarkably, co-occurring EGFR and TP53 mutations were grouped as MC1. EGFR+TP53 mutations showed upregulation of peptide synthesis and higher synthetic processes, as well as differences in myeloid and T/NK cells compared to EGFR mutations. In T/NK cells, EGFR+TP53 mutations showed a higher expression of features related to cell activity and differentiation, whereas EGFR mutations showed the opposite. Conclusion Our research indicates a close association between mutation types and tumor microenvironment in NSCLC, offering insights into personalized approaches for cancer diagnosis and treatment.

Serological tests for Helicobacter pylori needs local validation as the diagnostic accuracy may vary depending on the prevalence of H.pylori. This study examined the diagnostic performance of two ELISA, GastroPanel® (GastroPanel ELISA; Biohit Oyj) and GENE-DIA® (GENEDIA® H. pylori ELISA, Green Cross Co.) in Korean population. One thousand seventy seven patients who visited for esophagogastroduodenoscopy between 2013 and 2023 were prospectively enrolled, and serum samples from the subjects were tested using both GastroPanel® and GENEDIA® . The two tests were compared for their diagnostic accuracy in detecting atrophic gastritis (AG), intestinal metaplasia (IM), gastric adenoma (GA), and gastric cancer (GC), and the positivity rates by age and sexwere observed. There was substantial correlation (Pearson coefficient [r] = 0.512, P < 0.001) and agreement (Cohen’s Kappa coefficient [κ] = 0.723, P < 0.001) between the results obtained using GastroPanel® and GENEDIA® . The test results from the two kits did not match perfectly with a discrepancy observed in approximately 16% of cases, that 67 subjects were positive only on GENE-DIA® while 75 subjects were positive only on GastroPanel® . The area under receiver operating characteristic curve for AG, IM, GA,and GC using GastroPanel® were 0.666, 0.635, 0.540, and 0.575, while the results tested using GENEDIA® were 0.649, 0.604, 0.553, and 0.555, respectively, without significant difference between the two results. GastroPanel® and GENEDIA® showed similar performance in terms of diagnostic accuracy; but the test results did not match perfectly. A large-scale validation study in Koreansis needed.

Background: The role of apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) in adipose tissue remains poorly understood. This study investigates adipose tissue dysfunction in heterozygous APE1/Ref-1 deficiency (APE1/Ref-1+/-) mice, focusing on changes in adipocyte physiology, oxidative stress, adipokine regulation, and adipose tissue distribution. Methods: APE1/Ref-1 mRNA and protein levels in white adipose tissue (WAT) were measured in APE1/Ref-1+/- mice, compared to their wild-type (APE1/Ref-1+/+) controls. Oxidative stress was assessed by evaluating reactive oxygen species (ROS) levels. Histological and immunohistochemical analyses were conducted to observe adipocyte size and macrophage infiltration of WAT. Adipokine expression was measured, and micro-magnetic resonance imaging (MRI) was used to quantify abdominal fat volumes. Results: APE1/Ref-1+/- mice exhibited significant reductions in APE1/Ref-1 mRNA and protein levels in WAT and liver tissue. These mice also showed elevated ROS levels, suggesting a regulatory role for APE1/Ref-1 in oxidative stress in WAT and liver. Histological and immunohistochemical analyses revealed hypertrophic adipocytes and macrophage infiltration in WAT, while Oil Red O staining demonstrated enhanced ectopic fat deposition in the liver of APE1/Ref-1+/- mice. These mice also displayed altered adipokine expression, with decreased adiponectin and increased leptin levels in the WAT, along with corresponding alterations in plasma levels. Despite no significant changes in overall body weight, microMRI assessments demonstrated a significant increase in visceral and subcutaneous abdominal fat volumes in APE1/Ref-1+/- mice. Conclusion APE1/Ref-1 is crucial in adipokine regulation and mitigating oxidative stress. These findings suggest its involvement in adipose tissue dysfunction, highlighting its potential impact on abdominal fat distribution and its implications for obesity and oxidative stress-related conditions.

Background: The role of apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) in adipose tissue remains poorly understood. This study investigates adipose tissue dysfunction in heterozygous APE1/Ref-1 deficiency (APE1/Ref-1+/-) mice, focusing on changes in adipocyte physiology, oxidative stress, adipokine regulation, and adipose tissue distribution. Methods: APE1/Ref-1 mRNA and protein levels in white adipose tissue (WAT) were measured in APE1/Ref-1+/- mice, compared to their wild-type (APE1/Ref-1+/+) controls. Oxidative stress was assessed by evaluating reactive oxygen species (ROS) levels. Histological and immunohistochemical analyses were conducted to observe adipocyte size and macrophage infiltration of WAT. Adipokine expression was measured, and micro-magnetic resonance imaging (MRI) was used to quantify abdominal fat volumes. Results: APE1/Ref-1+/- mice exhibited significant reductions in APE1/Ref-1 mRNA and protein levels in WAT and liver tissue. These mice also showed elevated ROS levels, suggesting a regulatory role for APE1/Ref-1 in oxidative stress in WAT and liver. Histological and immunohistochemical analyses revealed hypertrophic adipocytes and macrophage infiltration in WAT, while Oil Red O staining demonstrated enhanced ectopic fat deposition in the liver of APE1/Ref-1+/- mice. These mice also displayed altered adipokine expression, with decreased adiponectin and increased leptin levels in the WAT, along with corresponding alterations in plasma levels. Despite no significant changes in overall body weight, microMRI assessments demonstrated a significant increase in visceral and subcutaneous abdominal fat volumes in APE1/Ref-1+/- mice. Conclusion APE1/Ref-1 is crucial in adipokine regulation and mitigating oxidative stress. These findings suggest its involvement in adipose tissue dysfunction, highlighting its potential impact on abdominal fat distribution and its implications for obesity and oxidative stress-related conditions.

Serological tests for Helicobacter pylori needs local validation as the diagnostic accuracy may vary depending on the prevalence of H.pylori. This study examined the diagnostic performance of two ELISA, GastroPanel® (GastroPanel ELISA; Biohit Oyj) and GENE-DIA® (GENEDIA® H. pylori ELISA, Green Cross Co.) in Korean population. One thousand seventy seven patients who visited for esophagogastroduodenoscopy between 2013 and 2023 were prospectively enrolled, and serum samples from the subjects were tested using both GastroPanel® and GENEDIA® . The two tests were compared for their diagnostic accuracy in detecting atrophic gastritis (AG), intestinal metaplasia (IM), gastric adenoma (GA), and gastric cancer (GC), and the positivity rates by age and sexwere observed. There was substantial correlation (Pearson coefficient [r] = 0.512, P < 0.001) and agreement (Cohen’s Kappa coefficient [κ] = 0.723, P < 0.001) between the results obtained using GastroPanel® and GENEDIA® . The test results from the two kits did not match perfectly with a discrepancy observed in approximately 16% of cases, that 67 subjects were positive only on GENE-DIA® while 75 subjects were positive only on GastroPanel® . The area under receiver operating characteristic curve for AG, IM, GA,and GC using GastroPanel® were 0.666, 0.635, 0.540, and 0.575, while the results tested using GENEDIA® were 0.649, 0.604, 0.553, and 0.555, respectively, without significant difference between the two results. GastroPanel® and GENEDIA® showed similar performance in terms of diagnostic accuracy; but the test results did not match perfectly. A large-scale validation study in Koreansis needed.

Purpose: We aimed to comprehensively analyze the immune cell and stromal components of tumor microenvironment at the single-cell level and identify tumor heterogeneity among the major top-derived oncogene mutations in non-small cell lung cancer (NSCLC) using single-cell RNA sequencing (scRNA-seq) data. Materials and Methods: The scRNA-seq dataset utilized in this study comprised 64369 primary tumor tissue cells from 21 NSCLC patients, focusing on mutations in EGFR, ALK, BRAF, KRAS, TP53, and the wild-type. Results: Tumor immune microenvironment (TIM) analysis revealed differential immune responses across NSCLC mutation subtypes. TIM analysis revealed different immune responses across the mutation subtypes. Two mutation clusters emerged: KRAS, TP53, and EGFR+TP53 mutations (MC1); and EGFR, BRAF, and ALK mutations (MC2). MC1 showed higher tertiary lymphoid structures signature scores and enriched populations of C2-T-IL7R, C3-T/NK-CXCL4, C9-T/NK-NKG, and C1-B-MS4A1 clusters than cluster 2. Conversely, MC2 cells exhibited higher expression levels of TNF, IL1B, and chemokines linked to alternative immune pathways. Remarkably, co-occurring EGFR and TP53 mutations were grouped as MC1. EGFR+TP53 mutations showed upregulation of peptide synthesis and higher synthetic processes, as well as differences in myeloid and T/NK cells compared to EGFR mutations. In T/NK cells, EGFR+TP53 mutations showed a higher expression of features related to cell activity and differentiation, whereas EGFR mutations showed the opposite. Conclusion Our research indicates a close association between mutation types and tumor microenvironment in NSCLC, offering insights into personalized approaches for cancer diagnosis and treatment.

Background: The role of apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) in adipose tissue remains poorly understood. This study investigates adipose tissue dysfunction in heterozygous APE1/Ref-1 deficiency (APE1/Ref-1+/-) mice, focusing on changes in adipocyte physiology, oxidative stress, adipokine regulation, and adipose tissue distribution. Methods: APE1/Ref-1 mRNA and protein levels in white adipose tissue (WAT) were measured in APE1/Ref-1+/- mice, compared to their wild-type (APE1/Ref-1+/+) controls. Oxidative stress was assessed by evaluating reactive oxygen species (ROS) levels. Histological and immunohistochemical analyses were conducted to observe adipocyte size and macrophage infiltration of WAT. Adipokine expression was measured, and micro-magnetic resonance imaging (MRI) was used to quantify abdominal fat volumes. Results: APE1/Ref-1+/- mice exhibited significant reductions in APE1/Ref-1 mRNA and protein levels in WAT and liver tissue. These mice also showed elevated ROS levels, suggesting a regulatory role for APE1/Ref-1 in oxidative stress in WAT and liver. Histological and immunohistochemical analyses revealed hypertrophic adipocytes and macrophage infiltration in WAT, while Oil Red O staining demonstrated enhanced ectopic fat deposition in the liver of APE1/Ref-1+/- mice. These mice also displayed altered adipokine expression, with decreased adiponectin and increased leptin levels in the WAT, along with corresponding alterations in plasma levels. Despite no significant changes in overall body weight, microMRI assessments demonstrated a significant increase in visceral and subcutaneous abdominal fat volumes in APE1/Ref-1+/- mice. Conclusion APE1/Ref-1 is crucial in adipokine regulation and mitigating oxidative stress. These findings suggest its involvement in adipose tissue dysfunction, highlighting its potential impact on abdominal fat distribution and its implications for obesity and oxidative stress-related conditions.