Gene expression profiles from needle biopsies provide useful signatures of non-small cell lung carcinomas

Abstract

Gene expression profiles from DNA microarrays can provide molecular signatures that improve tumor classification, prognosis, and treatment options. While much of this work has focused on isolation of RNA from the resected tumor, fewer studies have utilized RNA from fine needle aspirates (FNA). In this pilot study we examined whether the gene signatures obtained from FNA samples would correlate with signatures taken from the resected tumor. Based on NSCLC gene expression profiles obtained from eleven sets of FNA and tumor samples we obtained a high concordance of FNA profiles matching their matched tumor sample. These results suggest that FNA samples may provide informative gene expression signatures regarding the potential aggressiveness of non-small-cell lung carcinomas.

Keywords: Gene expression profiles; Lung cancer; Needle biopsy; Staging.

Figure 1

Kaplan- Meier survival plot. Survival of the 11 patients in this study. Only two individuals have died during follow-up, consistent with the observation that most of these tumors were early stage NSCLCs (Table 1).

Figure 2

Condition Tree of the 22 GeneChip profiles compared based on tissue type. The 11 sets of gene expression profiles were compared using the Pearson correlation with average linkage. The tree details the relationship of the 22 profiles with the gene signals (red-high expression, green-low expression) shown for each of the 42093 genes that were analyzed. Of the 11 sets of profiles, 9 of them showed that the FNA profile was most similar to the profile from its matching tumor. Colorbar represents how the color changes relate to relative expression.

Figure 3

Examination of PTHLH and PLUNC relative expression across various histological NSCLCs. The 11 needle and 11 tumor profiles were grouped into one of four histological subtypes and gene expression levels averaged among each group. (A) PTHLH expression is high in both the needle and tumor squamous samples (n = 7) and lowest in the adenocarcinoma (n = 1) and adenosquamous samples (n = 2). All four probesets for PTHLH show similar expression patterns. (B) PLUNC probe set shows that highest expression in the adenocarcinoma samples (n = 2) and is also detected in the squamous cell needle and tumor samples (n = 7). The expression of PLUNC appears higher in needle samples compared to tumor samples in the adenocarcinoma and large cell profile. This may result from the fact that the needle biopsies contain some normal tissue and PLUNC is found expressed in normal lung tissue (Bingle, Cross et al. 2005). Colorbar represents how the color changes relate to relative expression.