Analysis of Orthologous Gene Expression between Human Pulmonary Adenocarcinoma and a Carcinogen-Induced Murine Model

Abstract

Human adenocarcinoma (AC) is the most frequently diagnosed human lung cancer, and its absolute incidence is increasing dramatically. Compared to human lung AC, the A/J mouse-urethane model exhibits similar histological appearance and molecular changes. We examined the gene expression profiles of human and murine lung tissues (normal or AC) and compared the two species' datasets after aligning approximately 7500 orthologous genes. A list of 409 gene classifiers (P value <0.0001), common to both species (joint classifiers), showed significant, positive correlation in expression levels between the two species. A number of previously reported expression changes were recapitulated in both species, such as changes in glycolytic enzymes and cell-cycle proteins. Unexpectedly, joint classifiers in angiogenesis were uniformly down-regulated in tumor tissues. The eicosanoid pathway enzymes prostacyclin synthase (PGIS) and inducible prostaglandin E(2) synthase (PGES) were joint classifiers that showed opposite effects in lung AC (PGIS down-regulated; PGES up-regulated). Finally, tissue microarrays identified the same protein expression pattern for PGIS and PGES in 108 different non-small cell lung cancer biopsies, and the detection of PGIS had statistically significant prognostic value in patient survival. Thus, the A/J mouse-urethane model reflects significant molecular details of human lung AC, and comparison of changes in orthologous gene expression may provide novel insights into lung carcinogenesis.

A Macrophage Gene Expression Signature Defines a Field Effect in the Lung Tumor Microenvironment

“…RNA was isolated from lung tissues or BAL derived cells (below) using Trizol Reagent (Invitrogen) and RNeasy kits (Qiagen), followed by quality control measures using UV spectra characteristics (NanoDrop) and Bioanalyzer (Agilent) for size and integrity of the total RNA (12). Total RNA (2-5 Ag from lung tissues or 0.25-1 Ag from BAL cells) was converted to fragmented biotin-labeled cRNA by the Affymetrix kit reagents according to the manufacturer (Affymetrix).…”

“…One promise of gene expression microarray studies in lung cancer has been to develop novel approaches to diagnostics for disease classification and patient stratification into high probability treatment outcome groups (9)(10)(11)(12). This overall strategy has found considerable success in the treatment of breast cancer, moving from research tool to clinical diagnostics, to identify best treatment outcome and recurrence using a 70-gene panel (MammaPrint; ref.…”

“…As a first step toward identifying biomarkers of early lung cancer, we used the well-characterized A/J mouse-urethane model of human adenocarcinoma (12,17). We reasoned that histologically appearing, normal lung tissue from urethane-treated mice would have an altered gene expression profile because of proximity to the tumor microenvironment, when compared with normal lung tissue from age-matched untreated animals.…”

The involvement of the transcription factor Yin Yang 1 in cancer development and progression

“…Fifteen publicly available gene expression datasets were analyzed. 28,[35][36][37][38][39][40][41][42][43][44][45][46][47][48] Gene expression patterns of YY1 in nine different types of tumor and the relative normal counterpart were extracted from the normalized datasets (Table 2). This analysis reveals that YY1 transcript levels are significantly higher in cancer tissues than in the relative normal counterparts for each cancer type analyzed.…”

BCR–ABL-mediated upregulation of PRAME is responsible for knocking down TRAIL in CML patients

“…HL-60 and K562 cells were obtained from Cutaneus melanoma (18) Figure 7 TRAIL is downmodulated in lung adenocarcinoma, melanoma and breast carcinoma, while PRAME is upregulated. Box plots showing decreased expression of TRAIL and increased expression of PRAME on datasets performed in lung adenocarcinoma (Beer et al, 2002;Stearman et al, 2005) …”