Validation of mitochondrial biomarkers and immune dynamics in polycystic ovary syndrome.

PROBLEM: Polycystic ovary syndrome (PCOS), a prevalent endocrine-metabolic disorder, presents considerable therapeutic challenges due to its complex and elusive pathophysiology. METHOD OF STUDY: We employed three machine learning algorithms to identify potential biomarkers within a training dataset, comprising GSE138518, GSE155489, and GSE193123. The diagnostic accuracy of these biomarkers was rigorously evaluated using a validation dataset using area under the curve (AUC) metrics. Further validation in clinical samples was conducted using PCR and immunofluorescence techniques. Additionally, we investigate the complex interplay among immune cells in PCOS using CIBERSORT to uncover the relationships between the identified biomarkers and various immune cell types. RESULTS: Our analysis identified ACSS2, LPIN1, and NR4A1 as key mitochondria-related biomarkers associated with PCOS. A notable difference was observed in the immune microenvironment between PCOS patients and healthy controls. In particular, LPIN1 exhibited a positive correlation with resting mast cells, whereas NR4A1 demonstrated a negative correlation with monocytes in PCOS patients. CONCLUSION: ACSS2, LPIN1, and NR4A1 emerge as PCOS-related diagnostic biomarkers and potential intervention targets, opening new avenues for the diagnosis and management of PCOS.

Impact of the new lung cancer staging system for a predominantly advanced-disease patient population.

INTRODUCTION: To investigate the feasibility and clinical impact of the 7th edition of the "Tumor, Node, Metastasis" (TNM) classification scheme in lung cancer as proposed by the International Association for the Study of Lung Cancer (IASLC) for non-small cell lung cancer. METHODS: We evaluated the feasibility of the new staging system in our routine biweekly multidisciplinary lung cancer staging conference compared with the 6th TNM staging in a prospective manner from April 2008 to June 2009. The impact of IASLC staging versus the 6th TNM staging was observed at three levels: change in substaging, staging, and clinical management (based on the discussion within the staging conference). RESULTS: From 348 patients discussed during these conferences, 226 eligible non-small cell lung cancer patients newly diagnosed within the study period were reviewed and clinically staged. The majority were elderly (median age, 67 years) and men (58%). Of these, 23 patients had different staging, and four patients had different substaging in the IASLC staging compared with the 6th TNM staging. An impact on clinical management was seen in 2.7% (6 of 226) of these patients because of coding ipsilateral different-lobe metastasis as T4 instead of M1. CONCLUSIONS: The new staging system was clinically feasible and resulted in some (27 of 226, 12%) differences in staging. An impact on clinical decision making was occasionally seen within our institutional practice. Further studies are needed to investigate the comprehensive and long-term impact of the new staging system.