Papillary thyroid carcinoma (PTC) is clinically heterogeneous. Apart from an association with ionizing radiation, the etiology and molecular biology of PTC is poorly understood. We used oligobased DNA arrays to study the expression profiles of eight matched pairs of normal thyroid and PTC tissues. Additional PTC tumors and other tissues were studied by reverse transcriptase-PCR and immunohistochemistry. The PTCs showed concordant expression of many genes and distinct clustered profiles. Genes with increased expression in PTC included many encoding adhesion and extracellular matrix proteins. Expression was increased in 8͞8 tumors for 24 genes and in 7͞8 tumors for 22 genes. Among these genes were several previously known to be overexpressed in PTC, such as MET, LGALS3, KRT19, DPP4, MDK, TIMP1, and FN1. The numerous additional genes include CITED1, CHI3L1, ODZ1, N33, SFTPB, and SCEL. Reverse transcriptase-PCR showed high expression of CITED1, CHI3L1, ODZ1, and SCEL in 6͞6 additional PTCs. Immunohistochemical analysis detected CITED1 and SFTPB in 49͞52 and 39͞52 PTCs, respectively, but not in follicular thyroid carcinoma and normal thyroid tissue. Genes underexpressed in PTC included tumor suppressors, thyroid function-related proteins, and fatty acid binding proteins. Expression was decreased in 7͞8 tumors for eight genes and decreased in 6͞8 tumors for 19 genes. We conclude that, despite its clinical heterogeneity, PTC is characterized by consistent and specific molecular changes. These findings reveal clues to the molecular pathways involved in PTC and may provide biomarkers for clinical use.

BackgroundLung cancer is the leading cause of cancer-related death in the United States. Nearly 50% of patients with stages I and II non-small cell lung cancer (NSCLC) will die from recurrent disease despite surgical resection. No reliable clinical or molecular predictors are currently available for identifying those at high risk for developing recurrent disease. As a consequence, it is not possible to select those high-risk patients for more aggressive therapies and assign less aggressive treatments to patients at low risk for recurrence.Methods and FindingsIn this study, we applied a meta-analysis of datasets from seven different microarray studies on NSCLC for differentially expressed genes related to survival time (under 2 y and over 5 y). A consensus set of 4,905 genes from these studies was selected, and systematic bias adjustment in the datasets was performed by distance-weighted discrimination (DWD). We identified a gene expression signature consisting of 64 genes that is highly predictive of which stage I lung cancer patients may benefit from more aggressive therapy. Kaplan-Meier analysis of the overall survival of stage I NSCLC patients with the 64-gene expression signature demonstrated that the high- and low-risk groups are significantly different in their overall survival. Of the 64 genes, 11 are related to cancer metastasis (APC, CDH8, IL8RB, LY6D, PCDHGA12, DSP, NID, ENPP2, CCR2, CASP8, and CASP10) and eight are involved in apoptosis (CASP8, CASP10, PIK3R1, BCL2, SON, INHA, PSEN1, and BIK).ConclusionsOur results indicate that gene expression signatures from several datasets can be reconciled. The resulting signature is useful in predicting survival of stage I NSCLC and might be useful in informing treatment decisions.

Acute myeloid leukemia (AML) is a heterogeneous group of diseases. Normal cytogenetics (CN) constitutes the single largest group, while trisomy 8 (؉8) as a sole abnormality is the most frequent trisomy. How trisomy contributes to tumorigenesis is unknown. We used oligonucleotide-based DNA microarrays to study global gene expression in AML؉8 patients with ؉8 as the sole chromosomal abnormality and AML-CN patients. CD34 ؉ cells purified from normal bone marrow (BM) were also analyzed as a representative heterogeneous population of stem and progenitor cells. Expression patterns of AML patients were clearly distinct from those of CD34 ؉ cells of normal individuals. We show that AML؉8 blasts overexpress genes on chromosome 8, estimated at 32% on average, suggesting gene-dosage effects underlying AML؉8. Systematic analysis by cellular function indicated upregulation of genes involved in cell adhesion in both groups of AML compared with CD34 ؉ blasts from normal individuals. Perhaps most interestingly, apoptosis-regulating genes were significantly down-regulated in AML؉8 compared with AML-CN. We conclude that the clinical and cytogenetic heterogeneity of AML is due to fundamental biological differences.