Recurrence prediction of lung adenocarcinoma using an immune gene expression and clinical data trained and validated support vector machine classifier.

Background: Immune microenvironment plays a critical role in cancer from onset to relapse. Machine learning (ML) algorithm can facilitate the analysis of lab and clinical data to predict lung cancer recurrence. Prompt detection and intervention are crucial for long-term survival in lung cancer relapse.

Inflammation in the tumor-adjacent lung as a predictor of clinical outcome in lung adenocarcinoma.

Approximately 30% of early-stage lung adenocarcinoma patients present with disease progression after successful surgical resection. Despite efforts of mapping the genetic landscape, there has been limited success in discovering predictive biomarkers of disease outcomes. Here we performed a systematic multi-omic assessment of 143 tumors and matched tumor-adjacent, histologically-normal lung tissue with long-term patient follow-up.

Pig-to-human heart xenotransplantation in two recently deceased human recipients.

Genetically modified xenografts are one of the most promising solutions to the discrepancy between the numbers of available human organs for transplantation and potential recipients. To date, a porcine heart has been implanted into only one human recipient. Here, using 10-gene-edited pigs, we transplanted porcine hearts into two brain-dead human recipients and monitored xenograft function, hemodynamics and systemic responses over the course of 66 hours.

Extracorporeal Membrane Oxygenation Impact on Host Transcriptomic Response in Severe Coronavirus.

Background: Evidence suggests that patients critically ill with COVID-19 have a dysregulated host immune response that contributes to end-organ damage. Extracorporeal membrane oxygenation (ECMO) has been used in this population with varying degrees of success. This study was performed to evaluate the impact of ECMO on the host immunotranscriptomic response in these patients.

Pleural fluid microbiota as a biomarker for malignancy and prognosis.

Malignant pleural effusions (MPE) complicate malignancies and portend worse outcomes. MPE is comprised of various components, including immune cells, cancer cells, and cell-free DNA/RNA. There have been investigations into using these components to diagnose and prognosticate MPE.

BAP1 is a novel regulator of HIF-1α.

is a powerful tumor suppressor gene characterized by haplo insufficiency. Individuals carrying germline mutations often develop mesothelioma, an aggressive malignancy of the serosal layers covering the lungs, pericardium, and abdominal cavity. Intriguingly, mesotheliomas developing in carriers of germline mutations are less aggressive, and these patients have significantly improved survival.

The extracellular matrix protein fibulin-3/EFEMP1 promotes pleural mesothelioma growth by activation of PI3K/Akt signaling.

Malignant pleural mesothelioma (MPM) is an aggressive tumor with poor prognosis and limited therapeutic options. The extracellular matrix protein fibulin-3/EFEMP1 accumulates in the pleural effusions of MPM patients and has been proposed as a prognostic biomarker of these tumors. However, it is entirely unknown whether fibulin-3 plays a functional role on MPM growth and progression.

The lung microbiome, peripheral gene expression, and recurrence-free survival after resection of stage II non-small cell lung cancer.

Background: Cancer recurrence after tumor resection in early-stage non-small cell lung cancer (NSCLC) is common, yet difficult to predict. The lung microbiota and systemic immunity may be important modulators of risk for lung cancer recurrence, yet biomarkers from the lung microbiome and peripheral immune environment are understudied. Such markers may hold promise for prediction as well as improved etiologic understanding of lung cancer recurrence.

Genomic Profiling of Lung Adenocarcinoma in Never-Smokers.

Purpose: Approximately 10%-40% of patients with lung cancer report no history of tobacco smoking (never-smokers). We analyzed whole-exome and RNA-sequencing data of 160 tumor and normal lung adenocarcinoma (LUAD) samples from never-smokers to identify clinically actionable alterations and gain insight into the environmental and hereditary risk factors for LUAD among never-smokers.

Methods: We performed whole-exome and RNA-sequencing of 88 and 69 never-smoker LUADs.

Mesothelioma Biomarkers: Discovery in Search of Validation.

Malignant pleural mesothelioma (MPM) is an asbestos-related neoplasm that can only be treated successfully when correctly diagnosed and treated early. The asbestos-exposed population is a high-risk group that could benefit from sensitive and specific blood- or tissue-based biomarkers. We review recent work with biomarker development in MPM and literature of the last 20 years on the most promising blood- and tissue-based biomarkers.

Mesothelioma Biomarkers: A Review Highlighting Contributions from the Early Detection Research Network.

Malignant pleural mesothelioma (MPM) is an asbestos-related neoplasm, which can be treated successfully only if correctly diagnosed and treated in early stages. The asbestos-exposed population serves as a high-risk group that could benefit from sensitive and specific blood- or tissue-based biomarkers. This review details the recent work with biomarker development in MPM and the contributions of the NCI Early Detection Research Network Biomarker Developmental Laboratory of NYU Langone Medical Center.

Tumor-draining lymph nodes demonstrate a suppressive immunophenotype in patients with non-small cell lung cancer assessed by endobronchial ultrasound-guided transbronchial needle aspiration: A pilot study.

Objectives: Tumor draining lymph nodes (TDLN) are key sites of early immunoediting in patients with non-small cell lung cancer (NSCLC) and play an important role in generating anti-tumor immunity. Immune suppression in the tumor microenvironment has prognostic implications and may predict therapeutic response. T cell composition of draining lymph nodes may reflect an immunophenotype with similar prognostic potential which could be measured during standard-of-care bronchoscopic assessment.

When RON MET TAM in Mesothelioma: All Druggable for One, and One Drug for All?

Malignant pleural mesothelioma (MPM) is an aggressive inflammatory cancer with a poor survival rate. Treatment options are limited at best and drug resistance is common. Thus, there is an urgent need to identify novel therapeutic targets in this disease in order to improve patient outcomes and survival times.

The Microbiome in Lung Cancer Tissue and Recurrence-Free Survival.

Background: Human microbiota have many functions that could contribute to cancer initiation and/or progression at local sites, yet the relation of the lung microbiota to lung cancer prognosis has not been studied.

Methods: In a pilot study, 16S rRNA gene sequencing was performed on paired lung tumor and remote normal samples from the same lobe/segment in 19 patients with non-small cell lung cancer (NSCLC). We explored associations of tumor or normal tissue microbiome diversity and composition with recurrence-free (RFS) and disease-free survival (DFS), and compared microbiome diversity and composition between paired tumor and normal samples.

A Subset of Mesotheliomas With Improved Survival Occurring in Carriers of BAP1 and Other Germline Mutations.

Purpose: We hypothesized that four criteria could help identify malignant mesotheliomas (MMs) most likely linked to germline mutations of BAP1 or of other genes: family history of MM, BAP1-associated cancers, or multiple malignancies; or age younger than 50 years.

Patients And Methods: Over the course of 7 years, 79 patients with MM met the four criteria; 22 of the 79 (28%) reported possible asbestos exposure. They were screened for germline BAP1 mutations by Sanger sequencing and by targeted next-generation sequencing (tNGS) for germline mutations in 55 additional cancer-linked genes.

Epigenetically regulated PAX6 drives cancer cells toward a stem-like state via GLI-SOX2 signaling axis in lung adenocarcinoma.

It remains unclear whether PAX6 acts as a crucial transcription factor for lung cancer stem cell (CSC) traits. We demonstrate that PAX6 acts as an oncogene responsible for induction of cancer stemness properties in lung adenocarcinoma (LUAD). Mechanistically, PAX6 promotes GLI transcription, resulting in SOX2 upregulation directly by the binding of GLI to the proximal promoter region of the SOX2 gene.

Involvement of Heparanase in the Pathogenesis of Mesothelioma: Basic Aspects and Clinical Applications.

Background: Mammalian cells express a single functional heparanase, an endoglycosidase that cleaves heparan sulfate and thereby promotes tumor metastasis, angiogenesis, and inflammation. Malignant mesothelioma is highly aggressive and has a poor prognosis because of the lack of markers for early diagnosis and resistance to conventional therapies. The purpose of this study was to elucidate the mode of action and biological significance of heparanase in mesothelioma and test the efficacy of heparanase inhibitors in the treatment of this malignancy.

Summarizing performance for genome scale measurement of miRNA: reference samples and metrics.

Background: The potential utility of microRNA as biomarkers for early detection of cancer and other diseases is being investigated with genome-scale profiling of differentially expressed microRNA. Processes for measurement assurance are critical components of genome-scale measurements. Here, we evaluated the utility of a set of total RNA samples, designed with between-sample differences in the relative abundance of miRNAs, as process controls.

Keap1 loss promotes Kras-driven lung cancer and results in dependence on glutaminolysis.

Treating KRAS-mutant lung adenocarcinoma (LUAD) remains a major challenge in cancer treatment given the difficulties associated with directly inhibiting the KRAS oncoprotein. One approach to addressing this challenge is to define mutations that frequently co-occur with those in KRAS, which themselves may lead to therapeutic vulnerabilities in tumors. Approximately 20% of KRAS-mutant LUAD tumors carry loss-of-function mutations in the KEAP1 gene encoding Kelch-like ECH-associated protein 1 (refs.

A Panel of Novel Detection and Prognostic Methylated DNA Markers in Primary Non-Small Cell Lung Cancer and Serum DNA.

To establish a novel panel of cancer-specific methylated genes for cancer detection and prognostic stratification of early-stage non-small cell lung cancer (NSCLC). Identification of differentially methylated regions (DMR) was performed with bumphunter on "The Cancer Genome Atlas (TCGA)" dataset, and clinical utility was assessed using quantitative methylation-specific PCR assay in multiple sets of primary NSCLC and body fluids that included serum, pleural effusion, and ascites samples. A methylation panel of 6 genes (, and ) was selected from TCGA dataset.

High-density array-CGH with targeted NGS unmask multiple noncontiguous minute deletions on chromosome 3p21 in mesothelioma.

We used a custom-made comparative genomic hybridization array (aCGH; average probe interval 254 bp) to screen 33 malignant mesothelioma (MM) biopsies for somatic copy number loss throughout the 3p21 region (10.7 Mb) that harbors 251 genes, including BRCA1 (breast cancer 1)-associated protein 1 (BAP1), the most commonly mutated gene in MM. We identified frequent minute biallelic deletions (<3 kb) in 46 of 251 genes: four were cancer-associated genes: SETD2 (SET domain-containing protein 2) (7 of 33), BAP1 (8 of 33), PBRM1 (polybromo 1) (3 of 33), and SMARCC1 (switch/sucrose nonfermentable- SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily c, member 1) (2 of 33).

Inhibition of the colony-stimulating-factor-1 receptor affects the resistance of lung cancer cells to cisplatin.

In the present work we show that multiple lung cancer cell lines contain cisplatin resistant cell subpopulations expressing the Colony-Stimulating-Factor-Receptor-1 (CSF-1R) and surviving chemotherapy-induced stress. By exploiting siRNA-mediated knock down in vitro and the use of an investigational CSF-1R TKI (JNJ-40346527) in vitro and in vivo, we show that expression and function of the receptor are required for the clonogenicity and chemoresistance of the cell lines. Thus, inhibition of the kinase activity of the receptor reduced the levels of EMT-associated genes, stem cell markers and chemoresistance genes.