flavin-adenine-dinucleotide and Lung-Neoplasms

Quantitative chemometric widefield endogenous fluorescence microscopy (CFM) maps the endogenous absolute chromophore concentration and spatial distribution in cells and tissue sections label-free from fluorescence color images under broadband excitation and detection. By quantifying the endogenous chromophores, including tryptophan, elastin, reduced nicotinamide adenine dinucleotide [NAD(P)H], and flavin adenine dinucleotide (FAD), CFM reveals the biochemical environment and subcellular structure. Here we show that the chromophore information entropy, marking its spatial distribution pattern of quantitative chemometric endogenous fluorescence at the microscopic scale, improves photonic lung cancer diagnosis with independent diagnostic power to the cellular metabolism biomarker. NAD(P)H and FAD's information entropy is found to decrease from normal to perilesional to cancerous tissue, whereas the information entropy for the redox ratios [FAD/tryptophan and FAD/NAD(P)H] is smaller for the normal tissue than both perilesional and cancerous tissue. CFM imaging of the specimen's inherent biochemical and structural properties eliminates the dependence on measurement details and facilitates robust, accurate diagnosis. The synergy of quantifying absolute chromophore concentration and information entropy achieves high accuracies for a three-class classification of lung tissue into normal, perilesional, and cancerous ones and a three-class classification of lung cancers into grade 1, grade 2, and grade 3 using a support vector machine, outperforming the chromophore concentration biomarkers.

Topics: Chemometrics; Entropy; Flavin-Adenine Dinucleotide; Fluorescence; Humans; Lung; Lung Neoplasms; NAD

Solute carrier family 2 (facilitated glucose/fructose transporter) member 5 (SLC2A5)-inhibited seven different molecular Pearson mutual-positive-correlation networks constructed by 24 overlapping molecules from 368 GRNInfer and 34 Pearson under SLC2A5 CC ≤-0.25 in low human normal adjacent tissues were compared with high lung adenocarcinoma. Based on GO, KEGG, GenMAPP, BioCarta, and disease databases, our result showed that low SLC2A5-inhibited network included Golgi apparatus of AP1M2_1; cell cycle of CUL7, SAC3D1; protein amino acid dephosphorylation of STYXL1; pro-B cell-cell differentiation of SOX4_3; and FAD biosynthesis of FLAD1. Thus, we propose low glucose transporter SLC2A5-inhibited human normal adjacent lung adenocarcinoma cytoplasmic pro-B cell development mechanism network through repression of protein amino acid dephosphorylation to FAD biosynthesis.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; B-Lymphocytes; Biosynthetic Pathways; Flavin-Adenine Dinucleotide; Gene Expression; Glucose Transporter Type 5; Humans; Lung; Lung Neoplasms

Mammalian selenocysteine-containing thioredoxin reductase (TR) isolated from HeLa cells and from human lung adenocarcinoma cells was separated into two major enzyme species by heparin-agarose affinity chromatography. The low-affinity enzyme forms that were not retained on heparin agarose showed strong crossreactivity in immunoblot assays with anti-rat liver TR polyclonal antibodies, whereas the high-affinity enzyme forms that were retained by the heparin column were not detected. Both low and high heparin-affinity enzyme forms contained FAD, were indistinguishable on SDS/PAGE analysis, and exhibited similar catalytic activities in the NADPH-dependent DTNB [5,5'-dithiobis(2-nitrobenzoate)] assay. The C-terminal amino acid sequences of 75Se-labeled tryptic peptides from lung adenocarcinoma low- and high heparin-affinity enzyme forms were identical to the predicted C-terminal sequence of human placental TR. These two determined peptide sequences were -Ser-Gly-Ala-Ser-Ile-Leu-Gln-Ala-Gly-Cys-Secys-(Gly). Occurrence of the Se-carboxymethyl derivative of radioactive selenocysteine in the position corresponding to TGA in the gene confirmed that UGA is translated as selenocysteine. The presence of cysteine followed by a reactive selenocysteine residue in this C-terminal region of the protein may explain some of the unusual properties of the mammalian TRs.

Topics: Adenocarcinoma; Amino Acid Sequence; Base Sequence; Binding Sites; Chromatography, Affinity; Chromatography, Gel; Chromatography, High Pressure Liquid; Dithionitrobenzoic Acid; Electrophoresis, Polyacrylamide Gel; Flavin-Adenine Dinucleotide; HeLa Cells; Heparin; Humans; Kinetics; Lung Neoplasms; Peptide Fragments; Placenta; Selenium; Selenocysteine; Thioredoxin-Disulfide Reductase; Tumor Cells, Cultured