Biomedical subjects

Mitsuhiro Tada

Publications and source records attributed to Mitsuhiro Tada.

At least 19 recordsLinked to original sources

PubMed2006

HOXD3-overexpression increases integrin alpha v beta 3 expression and deprives E-cadherin while it enhances cell motility in A549 cells.

We have previously shown that transduction of HOXD3, one of homeobox genes, into human lung cancer A549 cells enhances cell motility, invasion and metastasis. In the present study, we examined the roles of integrin beta3 which was up-regulated by HOXD3-overexpression in the HOXD3-induced motility of A549 cells. We first established integrin beta3-transfectants and compared their motile activity to those of the HOXD3-transfected, control-transfected and parental cells by three different assays. The integrin beta3-transfectants as well as the HOXD3-transfectants formed heterodimer with integrin alphav subunit, and showed highly motile activities assessed by haptotaxis or phagokinetic track assay compared to the control transfectants or parental cells. In vitro wound-healing assay revealed that migratory activities were graded as the HOXD3-transfectants > the integrin beta3-transfectants > the control transfectants or parental cells. E-cadherin was expressed in the integrin beta3-transfectants but not expressed in the HOXD3-transfectants. An addition of function-blocking antibody to E-cadherin into the wound-healing assay promoted the migratory activity of the integrin beta3-transfectants, suggesting that E-cadherin prevented the cells from dissociating from the wound edges. These results indicate that increased expression of integrin alphav beta3 and loss of E-cadherin by HOXD3-overexpression are responsible for the enhanced motility and dissociation.

Animals↗

PubMed2006

Establishment and characterization of human urothelial cancer xenografts in severe combined immunodeficient mice.

AIM: To establish and characterize a murine xenograft model of human urothelial cancer in severe combined immunodeficient (SCID) mice for therapeutic simulation. METHODS: Pieces of 30 freshly resected urothelial tumors (24 obtained from bladder and 6 from ureter or pelvis) were implanted subcutaneously into SCID mice, and xenograft tumors were passed in tumorigenic cases. At each passage, histopathology, TP53 mutational status assessed by yeast p53 functional assay, and the Ki-67 labeling index (LI) were examined to evaluate the preservation of original features. A growth delay assay after single-dose irradiation was performed in four representative xenografts. RESULTS: Tumor growth was observed in 18 mice (60%, 18/30). Histologically, 15 of the 18 were epithelial carcinomas similar to the original tumors, whereas the other 3 were Epstein-Barr virus-associated lymphoproliferative disease, resulting in a 50% (15/30) take rate. No correlation was found between the tumor take rate and the clinicopathologic features, TP53 mutational status, or Ki-67 LI of the patients' tumors. Of these 15 xenografts, 11 xenografts were passed from 3 to 10 generations. TP53 mutational status remained stable during the passages, and the Ki-67 LI of eight xenografts was within a range of 50% of the LI of the original tumors, although the other three xenografts increased by over 50%. Specific growth delay after irradiation, independent of the original tumor growth speed and Ki-67 LI, was observed in four xenografts. CONCLUSIONS: SCID mice are useful recipients for investigations of human urothelial cancer with a wide biological range. This easy-to-handle xenograft system can help to develop a better in vivo preclinical evaluation system for therapeutic agents as well as the investigation of tumor pathophysiology.

Animals↗

PubMed2006

Disordered expression of HOX genes in human non-small cell lung cancer.

We hypothesized that the disordered tissue architecture in cancer results from the cells executing the program designed during ontogeny in a spatio-temporally inappropriate manner. HOX genes are known as master regulators of embryonic morphogenesis, and encode transcription factors which regulate the transcription of the downstream genes to realize the program of body plan. In this study, we quantified the expression levels of 39 HOX genes in 41 human non-small cell lung cancer (non-SCLC) and non-cancerous lung tissues by a comprehensive analysis system based on the real-time RT-PCR method. We found that the expression levels of HOXA1, A5, A10 and C6 in squamous cell carcinoma tissues (and HOXA5 and A10 in adenocarcinoma tissues) were significantly higher than those in the non-cancerous tissues. Comparison of HOX gene expressions between adenocarcinoma and squamous cell carcinoma tissues showed higher expressions of HOXA1, D9, D10 and D11 in squamous cell carcinoma tissues than in adenocarcinoma tissues. Immunohistochemical analysis revealed that HOXA5 and A10 proteins were localized in the cytoplasm of tumor cells in both adenocarcinoma and squamous cell carcinoma tissues. These results suggest that the disordered patterns of HOX gene expressions were involved not only in the development of non-SCLC but also in the histologically aberrant diversity such as adenocarcinoma and squamous cell carcinoma.

Adult↗

PubMed2005

Clinical features of familial moyamoya disease.

OBJECTS: This study aims to clarify the genetic background of moyamoya disease by comparing clinical features between familial and sporadic cases to reveal the responsible genes for familial moyamoya disease. METHODS: This study included 155 Japanese patients with moyamoya disease, which included 24 familial cases (10 family pedigrees) and 131 sporadic cases. Clinical features were compared between the familial and sporadic cases. RESULTS AND CONCLUSION: A female preponderance was significantly more prominent in the familial than in the sporadic group (P=0.0421). Mean age at onset was significantly lower in familial than in sporadic cases (P=0.004). In eight parent-offspring pairs, mean age at onset was significantly lower in the second than in the first generation (P<0.0001). These results suggest that familial moyamoya disease is associated with genetic anticipation and female predominance and that a genetic analysis study focused on expanded triplet repeats may clarify the pathogenesis of the disease.

Adolescent↗

PubMed2005

Temporal change in mKIAA gene expression during the early stage of retinoic acid-induced neurite outgrowth.

mKIAA genes are mouse counterparts of human KIAA genes, which were isolated in our cDNA project and were functionally unknown at the time they were sequenced. Because KIAA/mKIAA genes were isolated mainly from cDNA libraries derived from brain tissues, they are thought to be important for the organization and function of the brain. To investigate the participation of mKIAA genes in neuronal phenomena, we analyzed retinoic acid-induced neurite outgrowth using an mKIAA oligonucleotide microarray. Focusing on the early stage of this outgrowth phenomenon, we analyzed temporal gene expression changes 1-24 h after treatment with retinoic acid and found several change patterns in 38 mKIAA genes. Among them, six were upregulated at 3 h and subsequently returned to the steady state. Supposing that these genes had important roles, we performed semi-quantitative RT-PCR analysis and confirmed the existence of temporal expression patterns in two genes (mKIAA0182 and mKIAA1039). Further computational analysis of the 38 genes enabled us to find the cellular pathway associated with 6 of them with high confidence. These results indicate that some mKIAA genes are apparently relevant to retinoic acid-induced neurite outgrowth.

Animals↗

PubMed2005

Functional analysis of p53 gene and the prognostic impact of dominant-negative p53 mutation in endometrial cancer.

In addition to the loss of function, mutant p53 can possess a dominant-negative effect on wild-type p53 and may also exert gain-of-function activity. It is not clear whether the functional status of p53 mutation contributes to differences in outcome in endometrial cancer. We collected a total of 92 RNA samples of high quality from endometrial cancer tissues, and the samples were subjected to yeast functional assay and sequencing for p53 mutations. The detected mutant p53 genes were further investigated for their dominant-negative activity using a yeast-based transdominance assay. p53 mutation was found in 24 out of 92 (26.1%) tumors, of which 10 exhibited no dominant-negative activity (recessive mutation) and 14 showed dominant-negative activity. Dominant-negative p53 mutation was related to advanced stages (p = 0.01), nonendometrioid type tumors (p = 0.01) and grade 3 tumors (p = 0.04). The patients with dominant-negative mutation had significantly shorter survival than patients with no mutation (p < 0.0001) and those with a recessive mutation (p = 0.01) in the p53 gene. No difference in survival was found between the patients with tumors harboring a recessive p53 mutation and those with tumors harboring a wild-type p53. Multivariate analysis revealed that dominant-negative p53 mutation (p = 0.019), FIGO stage (p = 0.0037) and histologic subtype (p = 0.014) were independently related to patient survival. Dominant-negative p53 mutation was the most important prognostic factor for stage III/IV endometrial cancer (p = 0.0023). In conclusion, dominant-negative p53 mutation is often found in advanced stages and aggressive histologic subtypes of endometrial cancer and it is a strong predictor of survival of patients with advanced endometrial cancer. To elucidate further the role of p53 mutation in endometrial cancer, it is necessary to investigate gain-of-function activity involving dominant-negative p53 mutant proteins.

Biological Assay↗

PubMed2005

p53-defective tumors with a functional apoptosome-mediated pathway: a new therapeutic target.

BACKGROUND: Although cancer cells appear to maintain the machinery for intrinsic apoptosis, defects in the pathway develop during malignant transformation, preventing apoptosis from occurring. How to specifically induce apoptosis in cancer cells remains unclear. METHODS: We determined the apoptosome activity and p53 status of normal human cells and of lung, colon, stomach, brain, and breast cancer cells by measuring cytochrome c-dependent caspase activation and by DNA sequencing, respectively, and we used COMPARE analysis to identify apoptosome-specific agonists. We compared cell death, cytochrome c release, and caspase activation in NCI-H23 (lung cancer), HCT-15 (colon cancer), and SF268 (brain cancer) cells treated with Triacsin c, an inhibitor of acyl-CoA synthetase (ACS), or with vehicle. The cells were mock, transiently, or stably transfected with genes for Triacsin c-resistant ACSL5, dominant negative caspase-9, or apoptotic protease activating factor-1 knockdown. We measured ACS activity and levels of cardiolipin, a mitochondrial phospholipid, in mock and ACSL5-transduced SF268 cells. Nude mice carrying NCI-H23 xenograft tumors (n = 10) were treated with Triacsin c or vehicle, and xenograft tumor growth was assessed. Groups were compared using two-sided Student t tests. RESULTS: Of 21 p53-defective tumor cell lines analyzed, 17 had higher apoptosome activity than did normal cells. Triacsin c selectively induced apoptosome-mediated death in tumor cells (caspase activity of Triacsin c-treated versus untreated SF268 cells; means = 1020% and 100%, respectively; difference = 920%, 95% CI = 900% to 940%; P<.001). Expression of ACSL5 suppressed Triacsin c-induced cytochrome c release and subsequent cell death (cell survival of Triacsin c-treated mock- versus ACSL5-transduced SF268 cells; means = 40% and 83%, respectively; difference = 43%, 95% CI = 39% to 47%; P<.001). ACS was also essential to the maintenance of cardiolipin levels. Finally, Triacsin c suppressed growth of xenograft tumors (relative tumor volume on day 21 of Triacsin c-treated versus untreated mice; means = 4.6 and 9.6, respectively; difference = 5.0, 95% CI = 2.1 to 7.9; P = .006). CONCLUSIONS: Many p53-defective tumors retain activity of the apoptosome, which is therefore a potential target for cancer chemotherapy. Inhibition of ACS may be a novel strategy to induce the death of p53-defective tumor cells.

Animals↗

PubMed2005

Altered expressions of HOX genes in human cutaneous malignant melanoma.

HOX genes act as master genes to control morphogenesis. In human, HOX genes form 4 clusters composing 9 to 11 HOX genes (39 genes in total) on different chromosomes. We hypothesized that aberrant expression of HOX genes was associated with development and subsequent progression of melanoma and that the 39 HOX gene expression pattern determined the sites where melanoma grew. The expression levels of 39 HOX genes in 15 human cutaneous melanoma specimens and 7 nevus pigmentosus specimens were quantified by a comprehensive analysis system based on the real-time RT-PCR method. We found that the expression levels of HOXA11, A13, B9, D12 and D13 in melanoma were higher than those in nevus pigmentosus and that the expression levels of HOXA11, B2 and C13 were significantly different between pT4 melanoma and pT1 to pT3 melanoma. It was most notable that the expression levels of HOXA1, A2, C4 and B13 in melanoma with distant metastasis were higher than those in melanoma without it. On the other hand, we found no relationship between HOX genes expression patterns and the growing sites of melanoma. These results indicated that the misexpressions of some specific HOX genes were implicated in melanoma genesis and metastasis but had no linkage with melanoma sites.

Adult↗

PubMed2005

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. MATERIALS AND 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. CONCLUSION: 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.

Adenocarcinoma, Mucinous↗

PubMed2005

Right- and left-sided colorectal cancers display distinct expression profiles and the anatomical stratification allows a high accuracy prediction of lymph node metastasis.

Accurate preoperative prediction of lymph node metastasis and degree of tumor invasion would facilitate an appropriate decision of the extent of surgical resection of cancers to reduce unnecessary complication or to minimize the risk of recurrence in patients. We analyzed gene expression profiles characteristic of the invasiveness of colorectal carcinoma in a total of 89 cases, using a cDNA array and pattern classification algorithms. We set binary classes for a panel of clinicopathologic parameters, each of which was divided at different levels for categories (discrete) or values (continuous). We searched an optimal combination of genes to discriminate the classes by using of 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). We used a sequential forward feature selection which additively searched a combination of genes, giving a minimal leave-one-out classification error rate of a k-nearest neighbor classifier. In the process of gene preselection, we found a remarkable difference in the expression pattern of genes according to the anatomical location of cancers. The difference was most prominent when the classes were set for cecum, ascending colon, transverse colon, and descending colon (CATD) versus sigmoid colon and rectum (SR). By stratifying these two locations, we were able to extract gene expression profiles characteristic of the classes of the presence versus absence of lymph node metastasis, lymphatic invasion, vascular invasion and degree of mural invasion, and pathological stages, with an accuracy of more than 90%. These results suggest that colorectal cancers harbor distinct molecular pathophysiological statuses according to their right-to-left locations, of which stratification is important for pattern classification of cDNA array data.

Adult↗

PubMed2005

Aberrant expression of HOX genes in human invasive breast carcinoma.

HOX genes are known not only as master genes that control the morphogenesis, but also as regulator genes that maintain tissue or organ specificity in the adult body. We hypothesized that dysregulated expression of HOX genes was associated with tumor development and malignant progression such as invasion and metastasis. In this study, we analyzed the expression patterns of 39 HOX genes in human invasive ductal breast cancer tissues and normal tissues by the real-time RT-PCR method. We found 11 HOX genes (HOXA1, A2, A3, A5, A9, C11, D3, D4, D8, D9 and D10) expression levels of which were significantly different between cancerous and normal tissues. All 10 genes except HOXC11 were expressed at lower levels in cancerous tissues than normal tissues. Comparing expression levels of each HOX gene among the different types of cancer tissues, the expression level of HOXB7 was lower in lymph node metastasis-positive cancer tissues than negative cancer tissues; those of HOXD12 and D13 were higher in progesterone receptor-positive cancer tissues than negative cancer tissues; and the expression level of HOXC5 was lower in cancerous tissues with mutated-type p53 than in normal and cancerous tissues with wild-type p53. These results suggest that the aberrant expression of HOX genes is related to the development of breast cancer and malignant behavior of cancer cells.

Adult↗

PubMed2005

[In silico and systematic molecular evolutionary analysis of human SIAH1b inactivation].

"Seven in absentia homolog" (SIAH) is E3 ubiquitin ligase gene. It is reported that mice have three SIAH homolog genes, Siah1a, Siah1b and Siah2, while men have SIAH1 and SIAH2 genes. It has recently been reported that, among these genes, mouse Siah1b gene is a direct target of p53. However, the nature of human "SIAH1b" gene remains unknown. In this study, we identified it on chromosome X by using a computed searching methods (in silico cloning). Using cDNA from human tissues, we attempted to amplify this region by PCR, but failed to amplify it. By analyzing the structure of human "SIAH1b" gene, we found that Alu was inserted immediately before its coding region, and that this gene had a number of base substitutions in its coding region, compared to its homolog genes in mouse or man. From these findings, we suggest that human "SIAH1b" gene had been inactivated by insertion of Alu, and estimate that the inactivation occurred about 30-58 million years ago from the substitution rates of base during evolution.

Animals↗

PubMed2004

Sequence analysis and bioinformatics analysis of chromosome 17q25 in familial moyamoya disease.

OBJECTS: The pathogenesis of moyamoya disease is still unknown. The present study aimed to find out the responsible genes that are located in the 17q25 locus. METHODS: Considering the function, we selected nine genes as candidates from a total of 65 genes identified in the 9-cM region of D17S785-D17S836 in chromosome 17q25, and performed sequence analysis on the DNA samples obtained from a pedigree of familial moyamoya disease, which showed a complete linkage to the region by a haplotype analysis. Also, we attempted to identify candidate genes that have not been known but might be functionally relevant to the disease among a total of 2,100 expressed sequence tag (EST) sequences using bioinformatics techniques. RESULTS AND CONCLUSION: The sequence analysis could detect no mutation in the nine genes. Nor could we identify a novel candidate gene by the EST analysis. Further studies using alternative approaches are warranted to clarify the pathogenesis of moyamoya disease.

Chromosomes, Human, Pair 17↗

PubMed2004

Expression of AIE-75 PDZ-domain protein induces G2/M cell cycle arrest in human colorectal adenocarcinoma SW480 cells.

AIE-75 has been known as a 75-kDa autoantigen detected in the serum of autoimmune enteropathy (AIE) and as a colon cancer-related antigen, and now designated as a gene causative of Usher syndrome type 1C hereditary syndromic hearing loss. It binds to a novel putative tumor suppressor MCC2 that is homologous to MCC (mutated in colon cancer) through a PSD-95/Dlg/ZO-1 (PDZ) domain. To clarify the functional role in colon cancer cells, we transfected AIE-75 gene into SW480 colon cancer cells which do not express AIE-75. Expression of AIE-75 suppressed growth of SW480 cells in vitro in correlation with the expression levels. It was due mainly to G2/M phase cell cycle arrest associated with mitotic slippage, resulting in emergence of hyperploid giant-nucleated or multi-nucleated cells. Screening of proteins that bound to PDZ domains of AIE-75 by a yeast two hybrid system showed that three serine/threonine phosphatase catalytic subunits (PP2AC-alpha, PP2AC-beta, and PPP6C) could bind to AIE-75. Since PP2AC is known to regulate G2/M checkpoint, we suggest that AIE-75 interacts with PP2AC and prevent cells to transit mitotic phase.

Adaptor Proteins, Signal Transducing↗

PubMed2004

Gene-expression profile changes correlated with tumor progression and lymph node metastasis in esophageal cancer.

PURPOSE: The purpose of this research was to identify molecular clues to tumor progression and lymph node metastasis in esophageal cancer and to test their value as predictive markers. EXPERIMENTAL DESIGN: We explored the gene expression profiles in cDNA array data of a 36-tissue training set of esophageal squamous cell carcinoma (ESCC) by using generalized linear model-based regression analysis and a feature subset selection algorithm. By applying the identified optimal feature sets (predictive gene sets), we trained and developed ensemble classifiers consisting of multiple probabilistic neural networks combined with AdaBoosting to predict tumor stages and lymph node metastasis. We validated the classifier abilities with 18 independent cases of ESCC. RESULTS: We identified 71 genes of 1289 cancer-related genes of which the expression correlated with tumor stages. Of the 71 genes, 47 significantly differed between the Tumor-Node-Metastasis pT1/2 and pT3/4 stages. Cell cycle regulators and transcriptional factors possibly promoting the growth of tumor cells were highly expressed in the early stages of ESCC, whereas adhesion molecules and extracellular matrix-related molecules possibly promoting invasiveness increased in the later stages. For lymph node metastasis, we identified 44 genes with predictive values, which included cell adhesion molecules and cell membrane receptors showing higher expression in node-positive cases and cell cycle regulators and intracellular signaling molecules showing higher expression in node-negative cases. The ensemble classifiers trained with the selected features predicted tumor stage and lymph node metastasis in the 18 validation cases with respective accuracies of 94.4% and 88.9%. This demonstrated the reproducibility and predictive value of the identified features. CONCLUSION: We suggest that these characteristic genes will provide useful information for understanding the malignant nature of ESCC as well as information useful for personalizing the treatments.

Algorithms↗

PubMed2004

Expression profiles of 39 HOX genes in normal human adult organs and anaplastic thyroid cancer cell lines by quantitative real-time RT-PCR system.

HOX genes are well known as master control genes in embryonic morphogenesis. We hypothesized that HOX genes give cells spatial information to maintain tissue- or organ-specificity in adult body and that the deregulated expression of HOX genes results in tumor development. We established a comprehensive analysis system to quantify expression of 39 human HOX genes based on the real-time reverse transcription PCR (RT-PCR) method. Analysis of 39 HOX genes of 20 normal adult organs by this system revealed that 5' HOX genes were expressed in organs in the caudal parts of the body, and that the more caudal regions the more numbers of HOX genes were expressed. It was also found that the expression patterns of HOX genes were more similar in the adjacent genes on the same cluster rather than in those belonging to the same paralogs. Compared with normal thyroid tissues, thyroid cancer cell lines showed the altered expression of some HOX genes, especially Abd-B homeobox family genes. Our results showed that HOX genes were organ-specifically expressed in adult body and that the deregulated expressions of Abd-B family genes were implicated in thyroid tumor development.

Actins↗

PubMed2004

Loss of p53 transcriptional activity in hepatocellular carcinoma evaluated by yeast-based functional assay: comparison with p53 immunohistochemistry.

We studied the transcriptional activity of p53 protein in 50 tissues of hepatocellular carcinoma (HCC) using a yeast functional assay. In this assay, red yeast colonies indicate that p53 protein cannot bind to its specific domain and has lost its transcriptional activity. We also clarified whether mutant p53 protein could inactivate wild-type p53 protein in a transdominant manner using a modified yeast assay. In addition, we examined whether immunohistochemically detectable p53 protein was functionally inactive. The incidence of p53 inactivation was significantly higher in tumors with capsular invasion. Out of 21 tumors diagnosed with p53 mutations, 11 exhibited >75% red colonies, and all contained missense mutations. In these tumors, p53 function was lost because there was supposedly no intact p53 gene on either allele. One missense mutant produced <60% red colonies, but it was also considered inactive as a p53 protein heterotetramer because of its transdominant activity. In 7 of the remaining 9 tumors, p53 was considered to be mutated on one allele and intact on the other. All of these 7 tumors contained nonsense or frameshift mutations and had no transdominant activity, which suggested that p53 function remained intact. Alternately, immunohistochemical analysis demonstrated that all of the tumors with missense mutations were positively immunostained, whereas those that contained nonsense or frameshift mutations were negatively stained. Consequently, positively immunostaining tumors mostly coincided with p53-inactive tumors. These yeast-based assays suggested that p53 function was retained in some mutant cases. Immunohistochemistry was helpful in screening functionally inactive p53 protein in HCCs.

Adult↗

PubMed2004

Prediction of lymph node metastasis by analysis of gene expression profiles in non-small cell lung cancer.

OBJECTIVE: Non-small cell lung carcinoma (NSCLC) is one of the leading causes of death in the world. Lymph node metastasis is not only an important factor in estimating the extent and the metastatic potential of an NSCLC but also in prognosticating the patient outcome. Preoperative prediction of lymph node metastasis might greatly facilitate the choice of appropriate surgical and medical options in patients with NSCLC. METHODS AND RESULTS: Using a cDNA array, we analyzed the expression profiles of 1,289 genes in 92 cancer tissues of NSCLC (37 squamous cell carcinomas and 55 adenocarcinomas). We divided the patients into two groups (classes) for each of various pathological factors, such as lymph node metastasis and pT-stage. For each pair of classes, we searched for an optimal combination of genes to classify the cases using a sequential forward selection algorithm starting from a gene set that showed significant difference in expression between the classes. We used the leave-one-out error cross-validation on a k-nearest neighbor classifier to sequentially choose the gene. Using the optimized set of genes, it was possible to stratify the patients for lymph node metastasis (pN-stage) and pT-stage at, respectively, 100% (23 genes) and 100% (55 genes) for cases with squamous cell carcinomas and 94% (43 genes) and 92% (35 genes) for those with adenocarcinomas. CONCLUSION: We conclude that expression profiling using feature selection provides a powerful means of stratification (personalization) of NSCLC patients and choice in treatment options, particularly for factors such as lymph node metastasis whose radiological diagnosis is presently incomplete.

Adenocarcinoma↗