Prediction of lymphatic invasion/lymph node metastasis, recurrence, and survival in patients with gastric cancer by cDNA array-based expression profiling.
BACKGROUND
We assessed the predictability of various classes of gastric carcinoma defined by clinicopathological parameters, such as invasiveness and clinical outcomes, using cDNA array data obtained from 54 cases.


METHODS
We searched an optimal combination of genes to discriminate the classes defined with the clinicopathological parameters by using a feature subset selection algorithm, which was applied to a set of genes preselected on the basis of statistical difference in expression (two-sided t test, P < or = 0.05). With the selected features (gene set), we evaluated the predictability of each parameter in a leave-one-out cross-validation test.


RESULTS
We successfully selected sets of genes for which the classifier predicted better versus worse overall survival (tumor-specific death) and tumor-free survival (recurrence), with respective classification rates of 94 and 92%. A contingency table analysis (chi2 test) and Cox proportional hazard model analysis revealed that lymph node metastasis is the most important factor (confounding factor) in patients' prognoses and risks of recurrence. The feature subset selection procedure successfully extracted expression patterns characteristic of lymph node metastasis and lymphatic vessel invasion, yielding 92 and 98% prediction accuracies for these respective factors.


CONCLUSIONS
We conclude that expression profiling using feature subset selection provides a powerful means of stratification of gastric cancer patients in regard to the prognostic factors. Further studies should be warranted to apply this method to personalization of the treatment options.
Teramoto
Ken-ichi
K
Department of Pathology/Pathophysiology, Division of Pathophysiological Science, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Tada
Mitsuhiro
M
Tamoto
Eiji
E
Abe
Motoki
M
Kawakami
Akiko
A
Komuro
Kazuteru
K
Matsunaga
Akihiro
A
Shindoh
Gaku
G
Takada
Minoru
M
Murakawa
Katsuhiko
K
Kanai
Motoshi
M
Kobayashi
Nozomi
N
Fujiwara
Yoshie
Y
Nishimura
Norihiro
N
Shirata
Katsutoshi
K
Takahishi
Toshiyuki
T
Ishizu
Akihiro
A
Ikeda
Hitoshi
H
Hamada
Jun-ichi
J
Kondo
Satoshi
S
Katoh
Hiroyuki
H
Moriuchi
Tetsuya
T
Yoshiki
Takashi
T
D002288:Adenocarcinoma, Mucinous / Q000235:genetics / Q000401:mortality / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020132:Anticipation, Genetic; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000401:mortality / Q000556:secondary*; D018279:Carcinoma, Signet Ring Cell / Q000235:genetics / Q000401:mortality / Q000556:secondary; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000401:mortality; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D011237:Predictive Value of Tests; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000401:mortality / Q000556:secondary*; D016019:Survival Analysis