Prognostication with Thyroid GuidePx in the context of tall cell variants.

Background: The tall cell variant of papillary thyroid cancer generally has a worse prognosis compared with the classical variant. Thyroid GuidePx is a genomic classifier capable of classifying papillary thyroid cancer into 3 molecular subtypes using fine-needle aspirate. Type 1 and 2 have low recurrence rates, particularly in early tumors (1-4 cm and N0).

A clinically useful and biologically informative genomic classifier for papillary thyroid cancer.

Clinical management of papillary thyroid cancer depends on estimations of prognosis. Standard care, which relies on prognostication based on clinicopathologic features, is inaccurate. We applied a machine learning algorithm () to 502 cases annotated by The Cancer Genome Atlas Project to derive an accurate molecular prognostic classifier.

Germline genetic contribution to the immune landscape of cancer.

Understanding the contribution of the host's genetic background to cancer immunity may lead to improved stratification for immunotherapy and to the identification of novel therapeutic targets. We investigated the effect of common and rare germline variants on 139 well-defined immune traits in ∼9000 cancer patients enrolled in TCGA. High heritability was observed for estimates of NK cell and T cell subset infiltration and for interferon signaling.

Immunohistochemical phenotyping of T cells, granulocytes, and phagocytes in the muscle of cancer patients: association with radiologically defined muscle mass and gene expression.

Background: Inflammation is a recognized contributor to muscle wasting. Research in injury and myopathy suggests that interactions between the skeletal muscle and immune cells confer a pro-inflammatory environment that influences muscle loss through several mechanisms; however, this has not been explored in the cancer setting. This study investigated the local immune environment of the muscle by identifying the phenotype of immune cell populations in the muscle and their relationship to muscle mass in cancer patients.

Clinical and biological characterization of skeletal muscle tissue biopsies of surgical cancer patients.

Background: Researchers increasingly use intraoperative muscle biopsy to investigate mechanisms of skeletal muscle atrophy in patients with cancer. Muscles have been assessed for morphological, cellular, and biochemical features. The aim of this study was to conduct a state-of-the-science review of this literature and, secondly, to evaluate clinical and biological variation in biopsies of rectus abdominis (RA) muscle from a cohort of patients with malignancies.

Knockout of USP19 Deubiquitinating Enzyme Prevents Muscle Wasting by Modulating Insulin and Glucocorticoid Signaling.

Muscle atrophy arises because of many chronic illnesses, as well as from prolonged glucocorticoid treatment and nutrient deprivation. We previously demonstrated that the USP19 deubiquitinating enzyme plays an important role in chronic glucocorticoid- and denervation-induced muscle wasting. However, the mechanisms by which USP19 exerts its effects remain unknown.

Sarcopenia and myosteatosis are accompanied by distinct biological profiles in patients with pancreatic and periampullary adenocarcinomas.

Introduction: Pancreatic and periampullary adenocarcinomas are associated with abnormal body composition visible on CT scans, including low muscle mass (sarcopenia) and low muscle radiodensity due to fat infiltration in muscle (myosteatosis). The biological and clinical correlates to these features are poorly understood.

Methods: Clinical characteristics and outcomes were studied in 123 patients who underwent pancreaticoduodenectomy for pancreatic or non-pancreatic periampullary adenocarcinoma and who had available preoperative CT scans.

Small RNAome profiling from human skeletal muscle: novel miRNAs and their targets associated with cancer cachexia.

Background: MicroRNAs (miRs) are small non-coding RNAs that regulate gene (mRNA) expression. Although the pathological role of miRs have been studied in muscle wasting conditions such as myotonic and muscular dystrophy, their roles in cancer cachexia (CC) are still emerging.

Objectives: The objectives are (i) to profile human skeletal muscle expressed miRs; (ii) to identify differentially expressed (DE) miRs between cachectic and non-cachectic cancer patients; (iii) to identify mRNA targets for the DE miRs to gain mechanistic insights; and (iv) to investigate if miRs show potential prognostic and predictive value.

New genetic signatures associated with cancer cachexia as defined by low skeletal muscle index and weight loss.

Background: Cachexia affects the majority with advanced cancer. Based on current demographic and clinical factors, it is not possible to predict who will develop cachexia or not. Such variation may, in part, be due to genotype.

Inactivation of the ubiquitin-specific protease 19 deubiquitinating enzyme protects against muscle wasting.

The ubiquitin system plays a critical role in muscle wasting. Previous work has focused on the roles of ubiquitination. However, a role for deubiquitination in this process has not been established.

Development of a new equation to estimate creatinine clearance in cancer patients.

Purpose: Determining renal function is important for chemotherapy eligibility and dosing. Measured creatinine clearance (mCrCl) is the gold standard but is cumbersome. Equations estimating CrCl (eCrCl) based on serum creatinine (SCr) produce widely varying estimates.

Effects of sample size on differential gene expression, rank order and prediction accuracy of a gene signature.

Top differentially expressed gene lists are often inconsistent between studies and it has been suggested that small sample sizes contribute to lack of reproducibility and poor prediction accuracy in discriminative models. We considered sex differences (69♂, 65 ♀) in 134 human skeletal muscle biopsies using DNA microarray. The full dataset and subsamples (n = 10 (5 ♂, 5 ♀) to n = 120 (60 ♂, 60 ♀)) thereof were used to assess the effect of sample size on the differential expression of single genes, gene rank order and prediction accuracy.

Prediction of skeletal muscle and fat mass in patients with advanced cancer using a metabolomic approach.

Urine and plasma metabolites originate from endogenous metabolic pathways in different organs and exogenous sources (diet). Urine and plasma were obtained from advanced cancer patients and investigated to determine if variations in lean and fat mass, dietary intake, and energy metabolism relate to variation in metabolite profiles. Patients (n = 55) recorded their diets for 3 d and after an overnight fast they were evaluated by DXA and indirect calorimetry.

Understanding the human salivary metabolome.

Saliva is a readily accessible biofluid that is important for the overall health, aiding in the chewing, swallowing, and tasting of food as well as the regulation mouth flora. As a first step to determining and understanding the human saliva metabolome, we have measured salivary metabolite concentrations under a variety of conditions in a healthy population with reasonably good oral hygiene. Using (1)H NMR spectroscopy, metabolite concentrations were measured in resting (basal) and stimulated saliva from the same subject and compared in a cohort of healthy male non-smoking subjects (n = 62).