OW Ghim Siong

EGF hijacks miR-198/FSTL1 wound-healing switch and steers a two-pronged pathway toward metastasis

Published date : 21 Aug 2017

Epithelial carcinomas are well known to activate a prolonged wound-healing program that promotes malignant transformation. Wound closure requires the activation of keratinocyte migration via a dual-state molecular switch. This switch involves production of either the anti-migratory microRNA miR-198 or the pro-migratory follistatin-like 1 (FSTL1) protein from a single transcript; miR-198 expression in healthy skin is down-regulated in favor of FSTL1 upon wounding, which enhances keratinocyte migration and promotes re-epithelialization.

type
Journal Paper
journal
The Journal of Experimental Medicine, 2017,doi: 10.1084/jem.20170354
Impact Factor
11.991

Transposon insertional mutagenesis in mice identifies human breast cancer susceptibility genes and signatures for stratification

Published date : 01 Mar 2017

Robust prognostic gene signatures and therapeutic targets are difficult to derive from expression profiling because of the significant heterogeneity within breast cancer (BC) subtypes. Here, we performed forward genetic screening in mice using Sleeping Beauty transposon mutagenesis to identify candidate BC driver genes in an unbiased manner, using a stabilized N-terminal truncated β-catenin gene as a sensitizer. We identified 134 mouse susceptibility genes from 129 common insertion sites within 34 mammary tumors.

type
Journal Paper
journal
Proceedings of the National Academy of Sciences of the Unites States of America, PNAS, Vol. 114, No. 11, E2215–E2224, doi: 10.1073/pnas.1701512114
Impact Factor
9.661

Big genomics and clinical data analytics strategies for precision cancer prognosis

Published date : 07 Nov 2016

The field of personalized and precise medicine in the era of big data analytics is growing rapidly. Previously, we proposed our model of patient classification termed Prognostic Signature Vector Matching (PSVM) and identified a 37 variable signature comprising 36 let-7b associated prognostic significant mRNAs and the age risk factor that stratified large high-grade serous ovarian cancer patient cohorts into three survival-significant risk groups.

type
Journal Paper
journal
Scientific Reports 6, 2016, Article no. 36493 (2016), doi:10.1038/srep36493

Big data and computational biology strategy for personalized prognosis

Published date : 24 May 2016

The era of big data and precision medicine has led to accumulation of massive datasets of gene expression data and clinical information of patients.

type
Journal Paper
journal
Oncotarget, 28 Jun 2016, Vol. 7, No. 26, Pg 40200-40220, doi: 10.18632/oncotarget.9571
Impact Factor
5.008

Genome and transcriptome delineation of two major oncogenic pathways governing invasive ductal breast cancer development

Published date : 10 Oct 2015

Invasive ductal carcinoma (IDC) is a major histo-morphologic type of breast cancer. Histological grading (HG) of IDC is widely adopted by oncologists as a prognostic factor. However, HG evaluation is highly subjective with only 50%–85% inter-observer agreements. Specifically, the subjectivity in the assignment of the intermediate grade (histologic grade 2, HG2) breast cancers (comprising ~50% of IDC cases) results in uncertain disease outcome prediction and sub-optimal systemic therapy.

type
Journal Paper
journal
Oncotarget 2015, DOI: 10.18632/oncotarget.5543
Impact Factor
6.359

Multiple signatures of a disease in potential biomarker space: Getting the signatures consensus and identification of novel biomarkers

Published date : 11 Jun 2015

Background: The lack of consensus among reported gene signature subsets (GSSs) in multi-gene biomarker
discovery studies is often a concern for researchers and clinicians. Subsequently, it discourages larger scale prospective studies, prevents the translation of such knowledge into a practical clinical setting and ultimately hinders the progress of the field of biomarker-based disease classification, prognosis and prediction.

type
Journal Paper
journal
BMC Genomics 2015, 16(Suppl 7):S2 doi:10.1186/1471-2164-16-S7-S2
Impact Factor
3.99

Abstract 3815: CHEK2 mutation is an adverse prognostic survival factor for patients diagnosed with high-grade serous ovarian carcinoma

Published date : 01 Oct 2014

High-grade serous ovarian carcinoma (HG-SOC) is a poorly prognosed and lethal gynecological disease where only 30% of patients survive beyond five years after initial pathologic diagnosis. However, the heterogeneity of HG-SOC tumors meant that patients often respond differently despite similar clinical intervention.

type
Journal Paper
journal
Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA, Cancer Research Oct 1, 2015 74, 3815, doi: 10.1158/1538-7445.AM2014-3815

Identification of two poorly prognosed ovarian carcinoma subtypes associated with CHEK2 germ-line mutation and non-CHEK2 somatic mutation gene signatures

Published date : 30 May 2014

High-grade serous ovarian cancer(HG-SOC), a major histologic type of epithelial ovarian cancer(EOC), is a poorly-characterized, heterogeneous and lethal disease where somatic mutations of TP53 are common and inherited loss-of-function mutations in BRCA1/2 predispose to cancer in 9.5–13% of EOC patients. However, the overall burden of disease due to either inherited or sporadic mutations is not known.

type
Journal Paper
journal
Cell Cycle, July 15 2014, Vol. 13, Issue 14, http://www.landesbioscience.com/journals/cc/toc/volume/13/issue/14/

Meta-analysis of transcriptome reveals let-7b as an unfavorable prognostic biomarker and predicts molecular and clinical sub-classes in high-grade serous ovarian carcinoma

Published date : 13 Jul 2013

High-grade serous ovarian carcinoma (HG-SOC) is a heterogeneous, poorly classified, lethal disease that frequently exhibits altered expressions of microRNAs. Let-7 family members are often reported as tumor suppressors; nonetheless, clinicopathological functions and prognostic values of individual let-7 family members have not been addressed in HG-SOC. In this work, we performed an integrative study to investigate the potential roles, clinicopathological functions and prognostic values of let-7 miRNA family in HG-SOC.

type
Journal Paper
journal
International Journal of Cancer 2013 Jul 3, doi: 10.1002/ijc.28371
Impact Factor
6.2

How to discriminate between potentially novel and considered biomarkers within molecular signature?

Published date : 15 Apr 2013

The lack of consensus among reported molecular (gene, protein, regulatory marker) signatures (MSs) in the literature is often an initial concern for researchers and subsequently it discourages larger scale prospective studies,prevent the translation of such knowledge into a practical clinical setting and ultimately hindering the progress of the field of

type
Conference Paper/Poster
journal
2013 IEEE Symposium on Computational Intelligence in Bioinformatics and Computational Biology (IEEE CIBCB 2013), April 15-19, Singapore