Activation of Angiogenesis Differs Strongly Between Pulmonary Carcinoids and Neuroendocrine Carinomas and Is Crucial for Carcinoid Tumourgenesis

Abstract

Background: Lung cancer still remains the leading cause of cancer for men after prostate cancer and breast cancer for women. Angiogenesis is considered a major microenvironment modifier. Material and Methods: Demographic data and study design; The study is based on a collective of twenty representative specimens of each tumour entity (Typical Carcinoid, Atypical Carcinoid, Large-Cell Neuroendocrine Carcinoma , Small Cell Lung Cancer) for mRNA expression analysis. The following methods were performed: RNA Extraction and RNA Integrity Assessment, NanoString CodeSet Design and Expression Quantification, NanoString Data Processing and Statistical Analysis. Results: KDR rendered significant association to aggressiveness of the tumour and decreases with increasing malignancy (p=0.049). A decreased expression of HIF1A and KDR mRNA as associated with a higher risk of tumour invasion in vessels (HIF1A: p=0.034; KDR: p=0.029). FIGF and HIF1A expression levels are significantly associated with progression-free survival (FIGF: p= 0.021; HIF1A: p= 0.049). CRHR2 and FLT4 are stronger expressed in female than in male patients (CRHR2: p=0.024, FLT4: p=0.004). FIGF expression is still significant between LCNEC and SCLC (p=0.023). FLT4 and KDR show highly significant association to one of the analysed groups (FLT4: p=0.001; KDR: p=0.006). Additionally, HIF1A expression differs significantly between these focus cohorts (p=0.018). Conclusion: We should consider for clinical practice application which factors affect most the tumour growth and distal metastasis, thereafter investigate easy to administer drugs with low side effects. Probably a cluster system of therapy should be established where a drug targets simultaneously different pathways of the same origin.

ACTB, CDKN1B, GAPDH, GRB2, RHOA and SDCBP Were Identified as Reference Genes in Neuroendocrine Lung Cancer via the nCounter Technology

“…Nevertheless, a large proportion of RNA fragments of ≥100 nt remain intact and can be detected reliably [2, 5]. This fragment length is sufficient to analyze such samples with the nCounter technology, which uses probe pairs binding to ~100 nt of the target regions [3, 5–7]. This approach makes it an ideal method for the analysis of degraded archival FFPE tissue.…”

“…Mediators of angiogenesis ( HIF1A , CRHR2 , KDR and FIGF ) correlated with decreased progression-free survival, poor outcome and more aggressive clinical behavior of NELC revealing potential therapy targets for tyrosine-kinase inhibitors and antibodies [7]. Another potent therapy target could be the 26S proteasome, because it showed significantly higher expression in NELC than in benign controls [22].…”

“…The CodeSet was designed to contain a total of 91 genes with different signature genes for each subgroup as described elsewhere [7, 14–16]. The CodeSet was designed and synthesized at NanoString Technologies, Seattle, USA (S1 Table for properties of the CodeSet).…”

“…The technology enables the detection of short target regions (~100 nt) making it an ideal method for analyzing fragmented nucleic acids from FFPE tissue. Fragments of 100 nt were reported to be detectable with nearly 100% efficiency [3, 5–7]. Reis et al .…”

Prognostic markers and response to vandetanib therapy in sporadic medullary thyroid cancer patients

“…Each sample was normalized using the sample-specific normalization factor. The normalized data were used for further statistical analysis (15).…”