I’m on a lung cancer and systems biology roll at the moment, although partly that’s just how the interesting data rolls in the literature.
Here’s some new food for thought. A group of respectable scientists published some fascinating data in PLOS Medicine (free article see reference below) entitled, “Nuclear Receptor Expression Defines a Set of Prognostic Biomarkers for Lung Cancer.”
Using PCR, they evaluated NR expression patterns associated with good and poor outcomes in patients with non-small cell lung cancer (NSCLC) and then validated the findings in lung adenocarcinomas (n=550) and squamous cell carcinoma (n=130) samples in three different analyses by comparing normal and lung cancer cells. Two important factors emerged from the analysis:
“The prognostic signature in tumors could be distilled to expression of two nuclear receptors, short heterodimer partner (SHP) and progesterone receptor, as single gene predictors of NSCLC patient survival time, including for patients with stage I disease.”
The SHP protein was the better predictor of outcomes in patients with stage I disease; those with strong SHP expression had better overall survival rates of approx. 70% at 100 months compared with 45% among people with low SHP expression. The survival curves in the paper were quite dramatic – check them out. Interestingly, the same signatures were also predictive of recurrence based on normal tissue samples from the patients with NSCLC. Progesterone receptor expression was, however, a much weaker predictor of any outcome based on this analysis.
Essentially, this means the study demonstrated:
“NR expression is strongly associated with clinical outcomes for patients with lung cancer, and this expression profile provides a unique prognostic signature for lung cancer patient survival time, particularly for those with early stage disease.”
What are nuclear receptors, you may be wondering?
“The NR superfamily contains 48 transcription factors (proteins that control the expression of other genes) that respond to several hormones and to diet-derived fats. NRs control many biological processes and are targets for several successful drugs, including some used to treat cancer.”
Still, it’s not something that immediately springs to mind as a possible or logical prognostic biomarker.
That said, out of the 48 transcription factors, two were found to be related to poorer patient outcomes. They were NGFIB3, a receptor associated with nerve growth factor, and NR3C2, a mineralocorticoid receptor protein:
“This study highlights the potential use of Nuclear Receptors (NRs) as a rational set of therapeutically tractable genes as theragnostic biomarkers, and specifically identifies short heterodimer partner and progesterone receptor in tumors, and NGFIB3 and MR in non-neoplastic lung epithelium, for future detailed translational study in lung cancer.”
Going forward, we still need to see more research to find out whether these particular NRs or others were involved with tumour development and growth. If they do, then NR’s may potentially offer new therapeutic targets for future research and development.
Jeong, Y., Xie, Y., Xiao, G., Behrens, C., Girard, L., Wistuba, I., Minna, J., & Mangelsdorf, D. (2010). Nuclear Receptor Expression Defines a Set of Prognostic Biomarkers for Lung Cancer PLoS Medicine, 7 (12) DOI: 10.1371/journal.pmed.1000378