Proteomic features of soft tissue tumours in adolescents and young adults.

Background: Adolescents and young adult (AYA) patients with soft tissue tumours including sarcomas are an underserved group with disparities in treatment outcomes.

Methods: To define the molecular features between AYA and older adult (OA) patients, we analysed the proteomic profiles of a large cohort of soft tissue tumours across 10 histological subtypes (AYA n = 66, OA n = 243), and also analysed publicly available functional genomic data from soft tissue tumour cell lines (AYA n = 5, OA n = 8).

Results: Biological hallmarks analysis demonstrates that OA tumours are significantly enriched in MYC targets compared to AYA tumours.

The proteomic landscape of soft tissue sarcomas.

Soft tissue sarcomas (STS) are rare and diverse mesenchymal cancers with limited treatment options. Here we undertake comprehensive proteomic profiling of tumour specimens from 321 STS patients representing 11 histological subtypes. Within leiomyosarcomas, we identify three proteomic subtypes with distinct myogenesis and immune features, anatomical site distribution and survival outcomes.

Uridine-derived ribose fuels glucose-restricted pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDA) is a lethal disease notoriously resistant to therapy. This is mediated in part by a complex tumour microenvironment, low vascularity, and metabolic aberrations. Although altered metabolism drives tumour progression, the spectrum of metabolites used as nutrients by PDA remains largely unknown.

Comprehensive characterization of immune landscape of Indian and Western triple negative breast cancers.

Purpose: Triple-negative breast cancer (TNBC) is a heterogeneous disease with a significant challenge to effectively manage in the clinic worldwide. Immunotherapy may be beneficial to TNBC patients if responders can be effectively identified. Here we sought to elucidate the immune landscape of TNBCs by stratifying patients into immune-specific subtypes (immunotypes) to decipher the molecular and cellular presentations and signaling events of this heterogeneous disease and associating them with their clinical outcomes and potential treatment options.

GREM1 is required to maintain cellular heterogeneity in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) shows pronounced epithelial and mesenchymal cancer cell populations. Cellular heterogeneity in PDAC is an important feature in disease subtype specification, but how distinct PDAC subpopulations interact, and the molecular mechanisms that underlie PDAC cell fate decisions, are incompletely understood. Here we identify the BMP inhibitor GREM1 as a key regulator of cellular heterogeneity in pancreatic cancer in human and mouse.

ARAF suppresses ERBB3 expression and metastasis in a subset of lung cancers.

RAF kinases are highly conserved serine/threonine kinases, and among the three RAF isoforms (ARAF, BRAF, and CRAF), the pathophysiological relevance of ARAF is not well defined. Here, we show that patients with lung cancer exhibit low expression of ARAF, which is associated with lymph node metastasis and poor patient survival. We uncover that depletion of ARAF promotes anchorage-independent growth and metastasis through activation of AKT signaling in a subset of lung cancer cells.

Proteogenomic Analysis of Breast Cancer Transcriptomic and Proteomic Data, Using De Novo Transcript Assembly: Genome-Wide Identification of Novel Peptides and Clinical Implications.

We have carried out proteogenomic analysis of the breast cancer transcriptomic and proteomic data, available at The Clinical Proteomic Tumor Analysis Consortium resource, to identify novel peptides arising from alternatively spliced events as well as other noncanonical expressions. We used a pipeline that consisted of de novo transcript assembly, six frame-translated custom database, and a combination of search engines to identify novel peptides. A portfolio of 4,387 novel peptide sequences initially identified was further screened through PepQuery validation tool (Clinical Proteomic Tumor Analysis Consortium), which yielded 1,558 novel peptides.

Expression profiling of cultured podocytes exposed to nephrotic plasma reveals intrinsic molecular signatures of nephrotic syndrome.

Background: Nephrotic syndrome (NS) is a common renal disorder in children attributed to podocyte injury. However, children with the same diagnosis have markedly variable treatment responses, clinical courses, and outcomes, suggesting molecular heterogeneity.

Purpose: This study aimed to explore the molecular responses of podocytes to nephrotic plasma to identify specific genes and signaling pathways differentiating various clinical NS groups as well as biological processes that drive injury in normal podocytes.

Salivary proteins from dysplastic leukoplakia and oral squamous cell carcinoma and their potential for early detection.

Dysplastic leukoplakia (LP) of the oral cavity is a potentially malignant condition for oral squamous cell carcinoma (OSCC), early detection of which remains an unmet clinical need. In an effort to develop non-invasive biomarker based method for early detection of the disease, differential proteomic profiling was carried out with the saliva from patients with risk habits and diagnosed with LP and those with lymph node negative and positive OSCC in comparison to healthy controls with risk habits. Ninety three proteins were observed at elevated level (≥1.

Targeted gene panel for genetic testing of south Indian children with steroid resistant nephrotic syndrome.

Background: Steroid resistant nephrotic syndrome (SRNS) is a genetically heterogeneous disease with significant phenotypic variability. More than 53 podocyte-expressed genes are implicated in SRNS which complicates the routine use of genetic screening in the clinic. Next generation sequencing technology (NGS) allows rapid screening of multiple genes in large number of patients in a cost-effective manner.

NLScore: a novel quantitative algorithm based on 3 dimensional structural determinants to predict the probability of nuclear localization in proteins containing classical nuclear localization signals.

The presence of a nuclear localization signal (NLS) in proteins can be inferred by the presence of a stretch of basic amino acids (KRKK). These NLSs are termed classical NLS (cNLS). However, only a fraction of proteins containing the cNLS pattern are transported into the nucleus by binding to importin α.

The "sausage" abscess: abscess of the liagamentum teres hepatis.

An abscess of the ligamentum teres hepatis is a very rare cause of acute abdomen and can present a diagnostic dilemma. A 40-year-old diabetic male presented with obstructive jaundice and cholangitis. An ill-defined, sausage-shaped, tender parasagittal supraumbilical mass was palpable on the right side.

Data on alteration of hormone and growth factor receptor profiles over progressive passages of breast cancer cell lines representing different clinical subtypes.

Human breast cancers are a highly heterogeneous group of tumours consisting of several molecular subtypes with a variable profile of hormone, growth factor receptors and cytokeratins [1]. Here, the data shows immunofluorescence profiling of four different cell lines belonging to distinct clinical subtypes of breast cancer. Post revival, the cell lines were passaged in culture and immunophenotyping was done for ER, HER-2, AR and EGFR.

β3 integrin promotes chemoresistance to epirubicin in MDA-MB-231 through repression of the pro-apoptotic protein, BAD.

Resistance to anthracycline based chemotherapy is a major limitation in the treatment of breast cancer, particularly of the triple negative sub-type that lacks targeted therapies. Resistance that arises from tumor-stromal interaction facilitated by integrins provides the possibility of targeted disruption. In the present study, we demonstrate that integrin β3 signaling inhibits apoptosis induced by a DNA-damaging chemotherapeutic agent, epirubicin, in MDA-MB-231 breast cancer cells.

High expression of integrin β6 in association with the Rho-Rac pathway identifies a poor prognostic subgroup within HER2 amplified breast cancers.

Integrin αvβ6 is involved in the transition from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) of the breast. In addition, integrin β6 (ITGB6) is of prognostic value in invasive breast cancers, particularly in HER2+ subtype. However, pathways mediating the activity of integrin αvβ6 in clinical progression of invasive breast cancers need further elucidation.