TY - JOUR
T1 - Analysis of paired primary lung and lymph node tumor cells
T2 - A model of metastatic potential by multiple genetic programs
AU - Hoang, Chuong D.
AU - Guillaume, Tenner J.
AU - Engel, Sean C.
AU - Tawfic, Sherif H.
AU - Kratzke, Robert A
AU - Maddaus, Michael A
PY - 2005
Y1 - 2005
N2 - Background: The current paradigm of metastasis proposes that rare cells within primary tumors acquire metastatic capability via sequential mutations, suggesting that metastases are genetically dissimilar from their primary tumors. We tested this hypothesis by examining the molecular differences, if any, between primary tumor cells and matched lymph node metastatic cells in human non-small-cell lung carcinoma specimens. Methods: We performed transcriptional profiling studies on malignant cells from 11 pairs of stage III tumors and their tumor-positive lymph nodes using multiple, complementary analytic techniques. To confirm the overall validity of microarray data, we used real-time polymerase chain reaction. Results: The molecular signature of nodal metastasis was a composite of two paradoxical, but not mutually exclusive, expression patterns: metastatic cells are: (1) different from their primary tumor cells based on a few genes and (2) genetically similar, overall, to their primary tumor cells. Consequently, we found a 27-gene subset sufficient to differentiate nodal metastatic cells from primary tumor cells. Conclusions: Thus, we concluded that a more accurate model of metastatic potential is based on a global primary tumor expression pattern along with the appearance of distinct metastatic variants. The 27-gene signature differentiating primary tumors from their metastatic cells may define non-small-cell lung carcinoma nodal metastatic potential.
AB - Background: The current paradigm of metastasis proposes that rare cells within primary tumors acquire metastatic capability via sequential mutations, suggesting that metastases are genetically dissimilar from their primary tumors. We tested this hypothesis by examining the molecular differences, if any, between primary tumor cells and matched lymph node metastatic cells in human non-small-cell lung carcinoma specimens. Methods: We performed transcriptional profiling studies on malignant cells from 11 pairs of stage III tumors and their tumor-positive lymph nodes using multiple, complementary analytic techniques. To confirm the overall validity of microarray data, we used real-time polymerase chain reaction. Results: The molecular signature of nodal metastasis was a composite of two paradoxical, but not mutually exclusive, expression patterns: metastatic cells are: (1) different from their primary tumor cells based on a few genes and (2) genetically similar, overall, to their primary tumor cells. Consequently, we found a 27-gene subset sufficient to differentiate nodal metastatic cells from primary tumor cells. Conclusions: Thus, we concluded that a more accurate model of metastatic potential is based on a global primary tumor expression pattern along with the appearance of distinct metastatic variants. The 27-gene signature differentiating primary tumors from their metastatic cells may define non-small-cell lung carcinoma nodal metastatic potential.
KW - Expression profiling
KW - Hierarchical clustering
KW - Laser capture microdissection
KW - Lymph node metastatic cells
KW - Metastasis
KW - Metastatic potential
KW - Microarray
KW - Model
KW - NSCLC
KW - Non-small-cell lung carcinoma
KW - RNA isolation
KW - Real-time quantitative RT-PCR
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U2 - 10.1016/j.cdp.2005.09.006
DO - 10.1016/j.cdp.2005.09.006
M3 - Article
C2 - 16289389
AN - SCOPUS:28744443137
SN - 0361-090X
VL - 29
SP - 509
EP - 517
JO - Cancer Detection and Prevention
JF - Cancer Detection and Prevention
IS - 6
ER -