NDLI: A ‘metastasis-prone’ signature for early-stage mismatch-repair proficient sporadic colorectal cancer patients and its implications for possible therapeutics

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A ‘metastasis-prone’ signature for early-stage mismatch-repair proficient sporadic colorectal cancer patients and its implications for possible therapeutics

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Clinical & Experimental Metastasis : Volume 27, Issue 1, January 2010

Clinical & Experimental Metastasis : Volume 26

Clinical & Experimental Metastasis : Volume 25

Clinical & Experimental Metastasis : Volume 24

Clinical & Experimental Metastasis : Volume 23

Clinical & Experimental Metastasis : Volume 22

Clinical & Experimental Metastasis : Volume 21

Clinical & Experimental Metastasis : Volume 20

Clinical & Experimental Metastasis : Volume 19

Clinical & Experimental Metastasis : Volume 18

Clinical & Experimental Metastasis : Volume 17

Clinical & Experimental Metastasis : Volume 16

Clinical & Experimental Metastasis : Volume 15

A ‘metastasis-prone’ signature for early-stage mismatch-repair proficient sporadic colorectal cancer patients and its implications for possible therapeutics

Content Provider	Springer Nature Link
Author	Hong, Yi Downey, Thomas Eu, Kong Weng Koh, Poh Koon Cheah, Peh Yean
Copyright Year	2010
Abstract	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.
Starting Page	83
Ending Page	90
Page Count	8
File Format	PDF
ISSN	02620898
Journal	Clinical & Experimental Metastasis
Volume Number	27
Issue Number	2
e-ISSN	15737276
Language	English
Publisher	Springer Netherlands
Publisher Date	2010-02-09
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Early stage colorectal cancer Genome-wide expression profiling Metastasis predictor Mismatch-repair proficient Connectivity map query Surgical Oncology Hematology Oncology Biomedicine general Cancer Research
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
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9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

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