Poster #331

PRECISE EARLY DETECTION OF LUNG CANCER AND IMMUNE CIRCUITOleg Kshivets

Kaluga Cancer Center, Russia, 67nd SSO Annual Cancer Symposium, March 12-16, 2014, Phoenix, AZ, the USA

Bootstrap Simulation: n=450

Early Lung Cancer=48; Norm=120;

Non-Malignant Pathology =282

Number of

Rank

Samples=3333

Kendall Tau-A P<

B-Cells 1 -0.041 0.05

Segmented Neutrophils 2 -0.041 0.05

Leucocytes 3 -0.040 0.05

CD8+VV+Cells

Monocytes

4

5

-0.034

-0.028

0.05

0.05

Objective: Significance of immune circuit in terms of early detection of lung cancer (LC) was inestigated.

Methods: In trial (1987-2013) consecutive cases after surgery, monitored 48 LC patients (LCP) (m=40, f=8; lobectomies=48) with pathologic stage IA (tomor size=1.6±0.4 cm; squamous=21, adenocarcinoma=25, large cell=2; T1N0M0=48; G1=16, G2=21, G3=11, 5-year survival=100%), 282 patients with lung non-malignant pathology (NMP) (m=188, f=94; pneumonectomies=5, lobectomies=179, segmentectomies=98; non-malignant tumors=100; abscess=112; tuberculoma=70) and 120 healthy donors (HD) (m=69, f=51) were reviewed. Variables selected for study were input levels of immunity blood parameters, sex, age, TNMG. Thawed aliquoted samples were evaluated for IgG, IgM, IgA, natural antibodies, circulating immune complexes. The percentage, absolute count and total population number (per human organism) of T-lymphocytes (CD3), B-lymphocytes (CD19), helper T-lymphocytes (CD4), suppressor/cytotoxic T-lymphocytes (CD8), killer cells (O-cells, K-cells or CD16), precursor T-cells (CD1), activated T-cells (CDw26), monocytes (CD64, CD13), helper/inducer T-lymphocytes (CD4+2H), contrsuppressor T-lymphocytes (CD8+VV), CD4/CD8, leukocytes, lymphocytes, polymorphonuclear and sticknuclear leukocytes were estimated. The laboratory blood studies also included input levels of NST (tests of oxygen dependent metabolism of neutrophils spontaneous and stimulated by Staphylococcus aureus or by Streptococcus pyogenes), index of stimulation of leukocytes by Staphylococcus aureus or Streptococcus pyogenes, index of thymus function, phagocytic number, phagocyte index, index of complete phagocytosis. Differences between groups were evaluated using discriminant analysis, clustering, nonlinear estimation, structural equation modeling, Monte Carlo, bootstrap simulation and neural networks computing.

Results: It was revealed that early detection of LC from NMP and HD (n=402) significantly depended on: CD4+2H, CD8+VV, CD4, B, CD16, monocytes (P=0.017-0.000). Neural networks computing, genetic algorithm selection and bootstrap simulation revealed relationships of early detection of LC and monocytes (rank=1), CD4+2H (rank=2), CD19 (3), CD8+VV (4), CD4 (5), CD16 (6). Correct detection of early LCP was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).

Neural Networks Simulation (Correct Classification=100%;

Error=0.0: Area Under ROC Curve=1.0; n=450):

Rank Sensitivity

Monocytes 1 1496.65

CD4+2H+Cells 2 1369.02

B-cells 3 1354.34

CD8+VV+Cells 4 1340.32

CD4+Cells 5 545.32

CD16+Cells 6 348.67

Significant Factors: T P

Segmented Neutrophils -2.70302 0.007132

Monocytes -3.07382 0.002242

B-cells -4.32866 0.000019

CD16+cells -2.23547 0.025879

CD8+VV+cells -2.09551 0.036687

Leucocytes -2.94928 0.003352

Discriminant Function Analysis Summary No. of vars in model: 10; Wilks' Lambda: .89179 approx. F (10,439)=5.3266 p< .0000

Wilks' - Lambda P

CD4+Cells 0.902078 0.024945

CD8+VV+Cells 0.902549 0.021866

CD4+2H+Cells 0.903516 0.016712

B-Cells 0.939965 0.000002

T-Cells 0.909554 0.003277

Monocytes 0.910621 0.002473

Lymphocytes 0.905700 0.009192

Stimulation Index by Staphylococcus aureus 0.903661 0.016058

NST stimulated by Staphylococcus aureus 0.907671 0.005407

NST spontaneous 0.901417 0.030056

0 2.55 7.510 12.515

CD8+VV+Cells02.557.51012.51517.5

T-Cells

000.10.10.20.20.30.30.40.40.50.50.60.60.70.70.80.80.90.911

Ear

ly C

ance

r---

NM

P, H

D

Ear

ly C

ance

r---

NM

P, H

D

P=0.023z=a+b/x+c/x 2̂+d/x 3̂+e/x 4̂+fy+gy 2̂+hy 3̂+iy 4̂

r 2̂=0.039149654 DF Adj r 2̂=0.019495897 FitStdErr=0.30565814 Fstat=2.246057a=0.64898982 b=0.19674838 c=-0.060515312 d=0.0044941272 e=-9.6163077e-05

f=0.10192687 g=-0.018714273 h=0.0012173861 i=-2.3777096e-05

PRECISE EARLY DETECTION OF LUNG CANCER AND IMMUNE CIRCUIT Oleg Kshivets

Poster #331

Conclusion: Early detection of LC from NMP and HD significantly depended on immune cell circuit.