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Gene expression profiles of tumor and paired normal lung tissues from primary non-small cell lung cancer (NSCLC) patients in Taiwan

ABSTRACT: Genome-wide expression profiling of NSCLC patients were done using Phalanx Human OneArray chip. The surgically resected tumor tissue and corresponding normal tissue were collected from 21 patients diagnosed with primary NSCLC admitted to Taipei Veterans General Hospital, Taiwan. In this study, we used cDNA microarray to detect gene expression profiling in tumor and corresponding normal samples from 21 NSCLC patients. There were 11 AD patients and 10 SQ patients. The patients consisted of 10 early stage patients (stages I and II) and 11 late stage patients (stages III and IV). Hybridization targets were prepared from total RNA and hybridized according to standard protocol using Phalanx Human OneArray chip (32,050 total features: 30968 human genome probes and 1082 experimental control probes).

ORGANISM(S): Homo sapiens

SUBMITTER: Lo FY

PROVIDER: S-ECPF-GEOD-21933 | biostudies-other | 2012

REPOSITORIES: biostudies-other

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Project description:BackgroundBrain metastases (BMs) are the most common central nervous system (CNS) malignant tumors, with rapid disease progression and extremely poor prognosis. The heterogeneity between primary lung cancers and BMs leads to the divergent efficacy of the adjuvant therapy response to primary tumors and BMs. However, the extent of heterogeneity between primary lung cancers and BMs, and the evolutionary process remains little known.MethodsTo deeply insight into the extent of inter-tumor heterogeneity at a single-patient level and the process of these evolutions, we retrospectively analyzed a total of 26 tumor samples from 10 patients with matched primary lung cancers and BMs. One patient underwent four times brain metastatic lesion surgery with diverse locations and one operation for the primary lesion. The genomic and immune heterogeneity between primary lung cancers and BMs were evaluated by utilizing whole-exome sequencing (WESeq) and immunohistochemical analysis.ResultsIn addition to inheriting genomic phenotype and molecular phenotype from the primary lung cancers, massive unique genomic phenotype and molecular phenotype were also observed in BMs, which revealed unimaginable complexity of tumor evolution and extensive heterogeneity among lesions at a single-patient level. By analysis of a multi-metastases case (Case 3) of cancer cells' subclonal composition, we found similar multiple subclonal clusters in the four spatial and temporal isolated brain metastatic focus, with the characteristics of polyclonal dissemination. Our study also verified that the expression level of immune checkpoints-related molecule Programmed Death-Ligand 1 (PD-L1) (P = 0.0002) and the density of tumor-infiltrating lymphocytes (TILs) (P = 0.0248) in BMs were significantly lower than that in paired primary lung cancers. Additionally, tumor microvascular density (MVD) also differed between primary tumors and paired BMs, indicating that temporal and spatial diversity profoundly contributes to the evolution of BMs heterogeneity.ConclusionOur study revealed the significance of temporal and spatial factors to the evolution of tumor heterogeneity by multi-dimensional analysis of matched primary lung cancers and BMs, which also provided novel insight for formulating individualized treatment strategies for BMs.

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Gene expression profiles of tumor and paired normal lung tissues from primary non-small cell lung cancer (NSCLC) patients in Taiwan

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