Malignant pleural effusion cells show aberrant glucose metabolism gene expression.
Malignant pleural effusion (MPE) accompanying lung adenocarcinoma indicates poor prognosis and early metastasis. This study aimed to identify genes related to MPE formation. Three tissue sample cohorts, seven from healthy lungs, 18 from stage I-III lung adenocarcinoma with adjacent healthy lung tissue and 13 from lung adenocarcinomas with MPE, were analysed by oligonucleotide microarray. The identified genes were verified by quantitative real-time PCR (qRT-PCR), immunohistochemical staining, and immunofluorescence confocal microscopy. 20 up- or down-regulated genes with a two-fold change in MPE cancer cells compared to healthy tissues were differentially expressed from early- to late-stage lung cancer. Of 13 genes related to cellular metabolism, aldolase A (ALDOA), sorbitol dehydrogenase (SORD), transketolase (TKT), and tuberous sclerosis 1 (TSC1) were related to glucose metabolism. qRT-PCR validated their mRNA expressions in pleural metastatic samples. Immunohistochemical staining confirmed aberrant TKT, ALDOA, and TSC1 expressions in tumour cells. Immunofluorescence confirmed TKT co-localisation and co-distribution of ALDOA with thyroid transcription factor 1-positive cancer cells. TKT regulated the proliferation, vascular endothelial growth factor secretion in vitro and in vivo vascular permeability of cancer cell. Glucose metabolic reprogramming by ALDOA, SORD, TKT and TSC1 is important in MPE pathogenesis.
Lin
C-C
CC
Division of Hematology/Oncology, Department of Internal Medicine, Hospital and Graduate Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 704, Taiwan.
Chen
L-C
LC
Tseng
V S
VS
Yan
J-J
JJ
Lai
W-W
WW
Su
W-P
WP
Lin
C-H
CH
Huang
C-Y F
CY
Su
W-C
WC
D000230:Adenocarcinoma / Q000150:complications; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D002199:Capillary Permeability / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015331:Cohort Studies; D005260:Female; D005634:Fructose-Bisphosphate Aldolase / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007064:L-Iditol 2-Dehydrogenase / Q000235:genetics; D008175:Lung Neoplasms / Q000150:complications; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics; D016066:Pleural Effusion, Malignant / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000235:genetics; D014174:Transketolase / Q000235:genetics; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
C000614412:NKX2-1 protein, human; D009687:Nuclear Proteins; C000624650:TSC1 protein, human; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins; D042461:Vascular Endothelial Growth Factor A; D007064:L-Iditol 2-Dehydrogenase; D014174:Transketolase; D005634:Fructose-Bisphosphate Aldolase; D005947:Glucose