Gene expression levels associated with impaired immune response and increased proliferation could serve as biomarkers for women following cervical cancer screening programmes.

Human papilloma virus (HPV) infections vary in their oncogenic potential, and whether an infection progresses to cervical intraepithelial neoplasia (CIN) also depends on the immune response. Therefore, the aim of the present study was to explore biomarkers related to the immune system and cell proliferation, in combination with HPV classified as having high (HOP) or low oncogenic potential (LOP), that can possibly guide a more accurate identification of women following cervical cancer screening programmes in need for immediate follow-up with a biopsy. A next-generation sequencing transcriptomic immune profile analysis applied to 28 persistent CIN3 lesions and 14 normal biopsies identified four genes, the immune markers and and the tumour markers and , as possible markers for differentiating between CIN3 and normal tissue.

Integrating Genetic Alterations and Histopathological Features for Enhanced Risk Stratification in Non-Muscle-Invasive Bladder Cancer.

Background: Urothelial carcinoma presents as non-muscle-invasive bladder cancer (NMIBC) in ~75% of primary cases. Addressing the limitations of the TNM and WHO04/16 classification systems, this study investigates genetic alterations, the mitotic activity index (MAI), and immunohistochemistry (IHC) markers CK20, p53, and CD25 as better prognostic biomarkers in NMIBC.

Methods: Using the Oncomine™ Focus Assay for targeted next-generation sequencing (NGS), 409 single-nucleotide variations (SNVs) and 193 copy number variations (CNVs) were identified across 287 patients with TaT1 tumors.

Quantitative proteomics reveals serum proteome alterations during metastatic disease progression in breast cancer patients.

Background: Tumor recurrence and metastatic progression remains the leading cause for breast cancer related mortalities. However, the proteomes of patient- matched primary breast cancer (BC) and metastatic lesions have not yet been identified, due to the lack of clinically annotated longitudinal samples. In this study, we evaluated the global-proteomic landscape of BC patients with and without distant metastasis as well as compared the proteome of distant metastatic disease with its corresponding primary BC, within the same patient.

New immune phenotypes for treatment response in high-grade serous ovarian carcinoma patients.

Despite advances in surgical and therapeutic approaches, high-grade serous ovarian carcinoma (HGSOC) prognosis remains poor. Surgery is an indispensable component of therapeutic protocols, as removal of all visible tumor lesions (cytoreduction) profoundly improves the overall survival. Enhanced predictive tools for assessing cytoreduction are essential to optimize therapeutic precision.

Outcomes of Patients With Graves Disease 25 Years After Initiating Antithyroid Drug Therapy.

Context: Graves disease (GD) is a leading cause of hyperthyroidism. Detailed investigations and predictors of long-term outcomes are missing.

Objective: This work aimed to investigate the outcomes in GD 25 years after initiating antithyroid drug treatment, including disease course, clinical and biochemical predictors of relapse, and quality of life.

Primary Treatment Effects for High-Grade Serous Ovarian Carcinoma Evaluated by Changes in Serum Metabolites and Lipoproteins.

High-grade serous ovarian carcinoma (HGSOC) is the most common and deadliest ovarian cancer subtype. Despite advances in treatment, the overall prognosis remains poor. Regardless of efforts to develop biomarkers to predict surgical outcome and recurrence risk and resistance, reproducible indicators are scarce.

Comprehensive ctDNA Measurements Improve Prediction of Clinical Outcomes and Enable Dynamic Tracking of Disease Progression in Advanced Pancreatic Cancer.

Purpose: Circulating tumor DNA (ctDNA) has emerged as a promising tumor-specific biomarker in pancreatic cancer, but current evidence of the clinical potential of ctDNA is limited. In this study, we used comprehensive detection methodology to explore the utility of longitudinal ctDNA measurements in patients with advanced pancreatic cancer.

Experimental Design: A targeted eight-gene next-generation sequencing panel was used to detect point mutations and copy-number aberrations (CNA) in ctDNA from 324 pre-treatment and longitudinal plasma samples obtained from 56 patients with advanced pancreatic cancer.

High-Grade Cervical Intraepithelial Neoplasia (CIN) Associates with Increased Proliferation and Attenuated Immune Signaling.

Implementation of high-risk human papilloma virus (HPV) screening and the increasing proportion of HPV vaccinated women in the screening program will reduce the percentage of HPV positive women with oncogenic potential. In search of more specific markers to identify women with high risk of cancer development, we used RNA sequencing to compare the transcriptomic immune-profile of 13 lesions with cervical intraepithelial neoplasia grade 3 (CIN3) or adenocarcinoma in situ (AIS) and 14 normal biopsies from women with detected HPV infections. In CIN3/AIS lesions as compared to normal tissue, 27 differential expressed genes were identified.

Metabolic consequences of perioperative oral carbohydrates in breast cancer patients - an explorative study.

Background: The metabolic consequences of preoperative carbohydrate load in breast cancer patients are not known. The present explorative study investigated the systemic and tumor metabolic changes after preoperative per-oral carbohydrate load and their influence on tumor characteristics and survival.

Methods: The study setting was on university hospital level with primary and secondary care functions in south-west Norway.

Influence of pre-operative oral carbohydrate loading vs. standard fasting on tumor proliferation and clinical outcome in breast cancer patients ─ a randomized trial.

Background: Conflicting results have been reported on the influence of carbohydrates in breast cancer.

Objective: To determine the influence of pre-operative per-oral carbohydrate load on proliferation in breast tumors.

Design: Randomized controlled trial.

Metabolomics Identifies Placental Dysfunction and Confirms Flt-1 (FMS-Like Tyrosine Kinase Receptor 1) Biomarker Specificity.

Clinical end-stage parameters define the pregnancy disorders preeclampsia and fetal growth restriction while classification of the underlying placental dysfunction is missing and urgently needed. Flt-1 (FMS-like tyrosine kinase receptor 1) is the most promising placenta-derived predictive biomarker for preeclampsia. We aimed to classify placental dysfunction in preeclampsia and fetal growth restriction at delivery by metabolic profiling and authenticate the biomarker Flt-1 for placental dysfunction.

Validation study of MARCKSL1 as a prognostic factor in lymph node-negative breast cancer patients.

Protein expression of Myristoylated alanine-rich C kinase substrate like-1 (MARCKSL1) has been identified as a prognostic factor in lymph-node negative (LN-) breast cancer patients. We aim to validate MARCKSL1 protein expression as a prognostic marker for distant metastasis-free survival (DMFS) in a new cohort of LN- breast cancer patients. MARCKSL1 expression was evaluated in 151 operable T1,2N0M0 LN- breast cancer patients by immunohistochemistry.

Metabolic profiles of placenta in preeclampsia using HR-MAS MRS metabolomics.

Introduction: Preeclampsia is a heterogeneous gestational disease characterized by maternal hypertension and proteinuria, affecting 2-7% of pregnancies. The disorder is initiated by insufficient placental development, but studies characterizing the placental disease components are lacking.

Methods: Our aim was to phenotype the preeclamptic placenta using high-resolution magic angle spinning nuclear magnetic resonance spectroscopy (HR-MAS MRS).

Distinct First Trimester Cytokine Profiles for Gestational Hypertension and Preeclampsia.

Objective: Gestational hypertension and preeclampsia involve dysregulated maternal inflammatory responses to pregnancy, but whether such responses differ between the disorders has not been determined. We aimed to investigate disease-specific early pregnancy serum cytokine profiles of women subsequently developing gestational hypertension or preeclampsia for new insight into the underlying pathogeneses and differences between the disorders.

Approach And Results: The study cohort consisted of 548 pregnant Norwegian women who were either multiparous with previous gestational hypertension or preeclampsia or were nulliparous.

First Trimester Urine and Serum Metabolomics for Prediction of Preeclampsia and Gestational Hypertension: A Prospective Screening Study.

Hypertensive disorders of pregnancy, including preeclampsia, are major contributors to maternal morbidity. The goal of this study was to evaluate the potential of metabolomics to predict preeclampsia and gestational hypertension from urine and serum samples in early pregnancy, and elucidate the metabolic changes related to the diseases. Metabolic profiles were obtained by nuclear magnetic resonance spectroscopy of serum and urine samples from 599 women at medium to high risk of preeclampsia (nulliparous or previous preeclampsia/gestational hypertension).

Metabolomic biomarkers in serum and urine in women with preeclampsia.

Objective: To explore the potential of magnetic resonance (MR) metabolomics for study of preeclampsia, for improved phenotyping and elucidating potential clues to etiology and pathogenesis.

Methods: Urine and serum samples from pregnant women with preeclampsia (n = 10), normal pregnancies (n = 10) and non-pregnant women (n = 10) matched by age and gestational age were analyzed with MR spectroscopy and subjected to multivariate analysis. Metabolites were then quantified and compared between groups.

PP002. Metabolomic biomarkers in serum and urine of preeclamptic women.

Introduction: Preeclampsia (PE) affects about 3% of pregnancies. The syndrome cannot be accurately predicted, and large variation complicates the search for early biomarkers. Metabolites are components of the metabolism; the chemical interactions in the body necessary for life.