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Biology subjects

Brunnström, H.

Publications and source records attributed to Brunnström, H..

2 recordsLinked to original sources

Histology-guided 3D virtual staining of microCT-imaged lung tissue via deep learning

Histologically stained tissue sections are considered the gold standard for studying microscopic anatomy and diagnosing disease in clinical practice. However, the processes of sectioning and staining are laborious, and the overall method relies on two-dimensional (2D) analysis. In contrast, X-ray-based virtual histology offers the advantage of virtual sectioning while retaining the full three-dimensional (3D) volumetric representation of the tissue. Nevertheless, its grayscale nature has prevented it to be readily utilized by pathologists who are accustomed to conventional histological stains. In this work, we present a histology-guided enhancement platform that can integrate the 3D information provided by synchrotron radiation phase-contrast microCT with the rich visual features characteristic of histological stains. We introduce a multi-stage microCT-histology co-registration method combined with a virtual staining deep neural network and demonstrate successful virtual histological staining of microCT human and mouse lung tissue that closely resembles standard histology. We evaluate our strategy on multiple histological stains and apply it to identify 3D collagen-based remodeling of pulmonary arteries in patients with pulmonary hypertension. Overall, this innovative enhancement pipeline has the potential to aid in the incorporation of microCT into clinical practice, and advance non-destructive 3D pathology for improved diagnostic efficiency and accuracy.

pathology↗

Multi-omic profiling of squamous cell lung cancer identifies metabolites and related genes associated with squamous cell carcinoma

BackgroundSquamous cell lung carcinoma (SqCC) is the second most common histological subtype of lung cancer. Besides -tumor-initiating and promoting DNA, RNA, and epigenetic alterations, aberrant tumor cell metabolism has been identified as one of the hallmarks of carcinogenesis. The aim of the current study was to identify SqCC-specific metabolites and key gene regulators that could eventually be used as new anticancer targets. MethodsTranscriptional (n=156), proteomics (n=118), and mass spectrometry-based metabolomic data (n=73) were gathered for a cohort of resected early-stage lung cancers representing all major histological subgroups. SqCC-specific differentially expressed genes were integrated with proteogenomic and metabolic data using genome scale metabolic models (GEMs). Findings were validated in cohorts of tumors, normal specimens, and cancer cell lines. In situ protein expression of SLC6A8 was investigated in 213 tumors. ResultsDifferential gene expression analysis identified 280 SqCC-specific genes, of which 57 were connected to metabolites through GEMs. Metabolic profiling identified 7 SqCC-specific metabolites, of which increased creatine and decreased phosphocholine levels matched to SqCC-specific elevated expression of SLC6A8 and decreased expression of CHKA, part of respective GEMs. Expression of both genes appeared tumor cell-associated, and in particular the elevated expression of SLC6A8 identified SqCC also in stage IV disease. ConclusionElevated creatine levels and the overexpression of its transporter protein SLC6A8 appear as a distinct metabolic feature of SqCC. Considering ongoing clinical trials focused on SLC6A8 inhibition in other malignancies, exploring SLC6A8 inhibition in SqCC appears motivated based on a metabolic addiction hypothesis.

cancer biology↗