myPlan Lung Cancer Test

myPlan lung cancer is a prognostic test developed by Myriad Genetic Laboratories that assesses the post-surgical cancer-specific mortality risk in patients with early stage lung cancer with adenocarcinoma histology. By measuring the expression of genes involved in cellular division, myPlan provides an objective measure of tumor aggressiveness.

Intended population:

  • pathological stage IA-IIB lung adenocarcinoma
  • complete resection (RO), negative margins
  • pre-surgical chemotherapy and radiation therapy naive

Cell Cycle Progression Score

myPlan provides a molecular measure of the aggressiveness of the patient’s tumor by analyzing 31 genes involved in cell cycle progression (CCP) and normalizing to 15 housekeeping genes.  The CCP Score was shown to be an independent predictor of five-year risk of mortality in four multinational published studies (Ref: Wistuba, Bueno, Rakha, Eguchi).

Phases of the Cell Cycle

31 Cell Cycle Progression genes analyzed in myPlan Lung Cancer

Mitotic phase

  • BUB1B
  • DLGAP5
  • C18orf24
  • CDCA3
  • CDC20
  • CDCA8
  • CENPM
  • CEP55
  • PBK
  • ASF1B
  • KIF11
  • NUSAP1
  • ASPM
  • PTTG1

Synthesis phase

  • RRM2
  • TOP2A
  • TK1
  • RAD54L
  • ORC6L
  • RAD51
  • DTL
  • MCM10
  • KIAA0101

Transitions

  • KIF20A (M-G1)
  • CDzqKN3 (G1-S)
  • FOXM1Z (S/G2-M)
  • PRC1 (G2-M)
  • BIRC5 (G2-M)
  • PLK1 (G2-M)
  • CDC2 (G2-M)
  • CENPF (G2-M)

Molecular Prognostic Score

Combining both the CCP Score and pathological stage in a validated algorithm, the myPlan Lung Cancer molecular Prognostic Score (mPS) delivers an easy to understand assessment of the risk associated with your patient’s disease. Patients with a high mPS are nearly twice as likely to succumb to their disease within five years of diagnosis compared to patients with a low mPS (35% vs 18%, respectively) (Ref: Bueno).

High mPS

Low mPS

mPS significantly predicts of 5-year cancer mortality
Patients with a high mPS have almost 2x greater mortality risk

Molecular Prognostic Score Algorithm

Prognostic score = 20* (0.33 * CCP score + 0.52 * stage)+15
Stage was used as numerical variable (1=IA, 2=1B, 3=IIA, 4=2B)

The algorithm for deriving a combined score was developed from the Director’s Consortium cohort microarray data and the training set from MDACC and IEO. CCP score and stage from the COX proportional hazard analysis were used to develop a model that would best predict 5-year lung cancer mortality. Stage was used as a numerical value and CCP score was used as a continuous variable. This algorithm is validated in two published studies. (Bueno, Rahka)

References:

  1. Bueno R, et al. Validation of a molecular and pathological model for five-year mortality risk in patients with early stage lung adenocarcinoma. J Thorac Oncol 2015; 10:67-73.
  2. Rakha E, et al. Stratification of resectable lung adenocarcinoma by molecular and pathological risk estimators. Eur J Cancer 2015; 51:1897-1903
  3. Eguchi E, et al. Validation of a cell cycle progression score for five-year mortality risk in patients with stage I lung adenocarcinoma. Presented at ASCO 2015.
  4. Wistuba II, Behrens C, Lombardi F, et al. Prognostic Marker in Early Stage Lung Adenocarcinoma. Clinical Cancer Research. November 15, 2013 19:6261-6271