We are analyzing https://link.springer.com/article/10.1007/s10585-010-9305-4.

Title:
A ‘metastasis-prone’ signature for early-stage mismatch-repair proficient sporadic colorectal cancer patients and its implications for possible therapeutics | Clinical & Experimental Metastasis
Description:
Metastasis is the major cause of cancer mortality. We aimed to find a metastasis-prone signature for early stage mismatch-repair proficient sporadic colorectal cancer (CRC) patients for better prognosis and informed use of adjuvant chemotherapy. The genome-wide expression profiles of 82 age-, ethnicity- and tissue-matched patients and healthy controls were analyzed using the Affymetrix U133 Plus 2 array. Metastasis-negative patients have 5 years or more of follow-up. A 10 × 10 two-level nested cross-validation design was used with several families of classification models to identify the optimal predictor for metastasis. The best classification model yielded a 54 gene-set (74 probe sets) with an estimated prediction accuracy of 71%. The specificity, sensitivity, negative and positive predictive values of the signature are 0.88, 0.58, 0.84 and 0.65, respectively, indicating that the gene-set can improve prognosis for early stage sporadic CRC patients. These 54 genes, including node molecules YWHAB, MAP3K5, LMNA, APP, GNAQ, F3, NFATC2, and TGM2, integrate multiple bio-functions in various compartments into an intricate molecular network, suggesting that cell-wide perturbations are involved in metastasis transformation. Further, querying the `Connectivity Map’ with a subset (70%) of these genes shows that Gly-His-Lys and securinine could reverse the differential expressions of these genes significantly, suggesting that they have combinatorial therapeutic effect on the metastasis-prone patients. These two perturbagens promote wound-healing, extracellular matrix remodeling and macrophage activation thus highlighting the importance of these pathways in metastasis suppression for early-stage CRC.
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Keywords {🔍}

cancer, article, google, scholar, pubmed, cas, colorectal, metastasis, expression, gene, clin, research, signature, patients, access, singapore, colon, privacy, cookies, content, data, clinical, early, genes, connectivity, sci, usa, res, publish, search, metastasisprone, mismatchrepair, proficient, sporadic, hong, cheah, stage, map, therapeutic, open, cancers, oncol, proc, nat, nature, including, information, log, find, journal,

Topics {✒️}

genome-wide expression profiles phosphatidylinositol 3-kinase-akt-mammalian target early-stage crc month download article/chapter peh yean cheah colorectal cancer research microarray gene-expression data distal colorectal cancers integrate multiple bio-functions perturbagens promote wound-healing human tri-peptide ghk cell-wide perturbations extracellular matrix remodeling gene expression signature gene expression profiles adjuvant colon cancer optimal predictor gene expression signatures gene-expression signatures metastasis-prone patients full article pdf gene expression patterns `connectivity map connectivity map �metastasis-prone’ signature metastasis-prone signature promoter–enhancer connectivity cancer cooperative groups privacy choices/manage cookies metastasis-negative patients clinical data retrieval colon cancer estimated prediction accuracy proximal msi cancers tissue-matched patients check access instant access colorectal surgery article hong connect small molecules gene expression susceptibility gene set clinical research european economic area positive predictive values oxaliplatin/5fu/lv updated efficacy results primary solid tumors comparative lesion sequencing predominantly postmenopausal cohort

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         description:Metastasis is the major cause of cancer mortality. We aimed to find a metastasis-prone signature for early stage mismatch-repair proficient sporadic colorectal cancer (CRC) patients for better prognosis and informed use of adjuvant chemotherapy. The genome-wide expression profiles of 82 age-, ethnicity- and tissue-matched patients and healthy controls were analyzed using the Affymetrix U133 Plus 2 array. Metastasis-negative patients have 5 years or more of follow-up. A 10 × 10 two-level nested cross-validation design was used with several families of classification models to identify the optimal predictor for metastasis. The best classification model yielded a 54 gene-set (74 probe sets) with an estimated prediction accuracy of 71%. The specificity, sensitivity, negative and positive predictive values of the signature are 0.88, 0.58, 0.84 and 0.65, respectively, indicating that the gene-set can improve prognosis for early stage sporadic CRC patients. These 54 genes, including node molecules YWHAB, MAP3K5, LMNA, APP, GNAQ, F3, NFATC2, and TGM2, integrate multiple bio-functions in various compartments into an intricate molecular network, suggesting that cell-wide perturbations are involved in metastasis transformation. Further, querying the `Connectivity Map’ with a subset (70%) of these genes shows that Gly-His-Lys and securinine could reverse the differential expressions of these genes significantly, suggesting that they have combinatorial therapeutic effect on the metastasis-prone patients. These two perturbagens promote wound-healing, extracellular matrix remodeling and macrophage activation thus highlighting the importance of these pathways in metastasis suppression for early-stage CRC.
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         Genome-wide expression profiling
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         Biomedicine
         general
         Oncology
         Hematology
         Surgical Oncology
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