scholarly journals A 12-Gene Genomic Instability Signature Predicts Clinical Outcomes in Multiple Cancer Types

2010 ◽  
Vol 25 (4) ◽  
pp. 219-228 ◽  
Author(s):  
Rama K.R. Mettu ◽  
Ying-Wooi Wan ◽  
Jens K. Habermann ◽  
Thomas Ried ◽  
Nancy Lan Guo
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Ovarian Cancer ◽  
Genomic Instability ◽  
Gene Expression Signature ◽  
Small Cell ◽  
Small Cell Lung ◽  
Multiple Cancer ◽  
Expression Signature ◽  
Cancer Types

Background and aims Genomic instability, as reflected in specific chromosomal aneuploidies and variation in the nuclear DNA content, is a defining feature of human carcinomas. It is solidly established that the degree of genomic instability influences clinical outcome. We have recently identified a 12-gene expression signature that discerned genomically stable from unstable breast carcinomas. This gene expression signature was also useful to predict, with high accuracy, the clinical course in independent multiple published breast cancer cohorts. From a biological point of view, this result confirmed the central role of genomic instability for a tumor's ability to adapt to external challenges and selective pressure, and hence for continued survival fitness. This prompted us to investigate whether this genomic instability signature could also predict clinical outcome in other cancer types of epithelial origin, including colorectal tumors, non-small cell lung carcinomas, and ovarian cancer. Results The results show that the gene expression signature that defines genomic instability and poor outcome in breast cancer contributes significantly more accurate (p<0.05 compared with random prediction) prognostic information in multiple cancer types independent of established clinical parameters. The 12-gene genomic instability signature stratified patients into high- and low-risk groups with distinct postoperative survival in three non-small cell lung cancer cohorts (n=637) in KaplanMeier analyses (log-rank p<0.05). It predicted recurrence in colon cancer patients (n=92) with an overall accuracy greater than 69% (p=0.04) in cross-cohort validation. It quantified relapse-free survival in ovarian cancer (n=124; log-rank p<0.05). Functional pathway analysis revealed interactions between the 12 signature genes and well-known cancer hallmarks. Conclusion The degree of genomic instability has diagnostic and prognostic implications. It is tempting to speculate that pursuing genomic instability therapeutically could provide entry points for a target that is unique to cancer cells.

scholarly journals A Gene Expression Signature Predicts Survival of Patients with Stage I Non-Small Cell Lung Cancer

PLoS Medicine ◽  
2006 ◽  
Vol 3 (12) ◽  
pp. e467 ◽  
Author(s):  
Yan Lu ◽  
William Lemon ◽  
Peng-Yuan Liu ◽  
Yijun Yi ◽  
Carl Morrison ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Gene Expression Signature ◽  
Small Cell ◽  
Stage I ◽  
Small Cell Lung ◽  
Expression Signature

scholarly journals Topsentinol L Trisulfate, a Marine Natural Product That Targets Basal-like and Claudin-Low Breast Cancers

Marine Drugs ◽  
2021 ◽  
Vol 19 (1) ◽  
pp. 41
Author(s):  
Nader N. El-Chaar ◽  
Thomas E. Smith ◽  
Gajendra Shrestha ◽  
Stephen R. Piccolo ◽  
Mary Kay Harper ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cell Lines ◽  
Gene Expression Signature ◽  
Marine Natural Product ◽  
Breast Cancer Cell Lines ◽  
Breast Cancers ◽  
Expression Signature ◽  
Her2 Breast Cancer ◽  
Cancer Types

Patients diagnosed with basal-like breast cancer suffer from poor prognosis and limited treatment options. There is an urgent need to identify new targets that can benefit patients with basal-like and claudin-low (BL-CL) breast cancers. We screened fractions from our Marine Invertebrate Compound Library (MICL) to identify compounds that specifically target BL-CL breast cancers. We identified a previously unreported trisulfated sterol, i.e., topsentinol L trisulfate (TLT), which exhibited increased efficacy against BL-CL breast cancers relative to luminal/HER2+ breast cancer. Biochemical investigation of the effects of TLT on BL-CL cell lines revealed its ability to inhibit activation of AMP-activated protein kinase (AMPK) and checkpoint kinase 1 (CHK1) and to promote activation of p38. The importance of targeting AMPK and CHK1 in BL-CL cell lines was validated by treating a panel of breast cancer cell lines with known small molecule inhibitors of AMPK (dorsomorphin) and CHK1 (Ly2603618) and recording the increased effectiveness against BL-CL breast cancers as compared with luminal/HER2+ breast cancer. Finally, we generated a drug response gene-expression signature and projected it against a human tumor panel of 12 different cancer types to identify other cancer types sensitive to the compound. The TLT sensitivity gene-expression signature identified breast and bladder cancer as the most sensitive to TLT, while glioblastoma multiforme was the least sensitive.

scholarly journals Gene expression signature for angiogenic and nonangiogenic non-small-cell lung cancer

Oncogene ◽  
2004 ◽  
Vol 24 (7) ◽  
pp. 1212-1219 ◽  
Author(s):  
Jiangting Hu ◽  
Fabrizio Bianchi ◽  
Mary Ferguson ◽  
Alfredo Cesario ◽  
Stefano Margaritora ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Gene Expression Signature ◽  
Small Cell ◽  
Small Cell Lung ◽  
Expression Signature

scholarly journals The gene expression signature of genomic instability in breast cancer is an independent predictor of clinical outcome

2009 ◽  
Vol 124 (7) ◽  
pp. 1552-1564 ◽  
Author(s):  
Jens K. Habermann ◽  
Jana Doering ◽  
Sampsa Hautaniemi ◽  
Uwe J. Roblick ◽  
Nana K. Bündgen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Clinical Outcome ◽  
Genomic Instability ◽  
Independent Predictor ◽  
Gene Expression Signature ◽  
Expression Signature

scholarly journals Topsentinol L Trisulfate, a new Marine Natural Product, that Targets Basal-like and Claudin-low Breast Cancers

2020 ◽  
Author(s):  
Nader N. El-Chaar ◽  
Thomas E. Smith ◽  
Gajendra Shrestha ◽  
Stephen R. Piccolo ◽  
Mary Kay Harper ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Marine Invertebrate ◽  
Human Tumor ◽  
Gene Expression Signature ◽  
Marine Natural Product ◽  
Breast Cancer Cell Lines ◽  
Expression Signature ◽  
Her2 Breast Cancer ◽  
Cancer Types

ABSTRACTBackgroundBreast cancer is a heterogeneous disease. Genomic studies have revealed five different intrinsic subtypes - Luminal A, Luminal B, HER2-enriched, Claudin-low, and Basal-like. Patients diagnosed with Basal-like or Claudin-low breast cancer (BL-CL) suffer from poor prognosis and limited treatment options. Hence, there is an urgent need to identify a new therapeutic lead that can benefit patients with BL-CL breast cancer.MethodsWe used a step-wise screening approach to screen 2778 HP20 fractions from our Marine Invertebrate Compound Library (MICL) to identify compounds that specifically target BL-CL breast cancer. We also performed biochemical investigations to study the effect of the compound in the signaling pathway. Finally, we generated a drug response gene-expression signature and projected it against a human tumor panel of 12 different cancer types to identify other cancer types sensitive to the compound.ResultsWe identified a previously unreported trisulfated sterol, topsentinol L trisulfate (TLT) that exhibits increased efficacy against BL-CL relative to Luminal/HER2+ breast cancer. Biochemical investigation of the effects of TLT on BL-CL revealed its ability to inhibit activation of AMPK and CHK1 and promote activation of p38. The importance of targeting AMPK and CHK1 in BL-CL was validated by treating a panel of breast cancer cell lines with known small molecule inhibitors of AMPK (Dorsomorphin) and CHK1 (Ly2603618) and recording the increased effectiveness against BL-CL compared to Luminal/HER2+ breast cancer. The TLT sensitivity gene-expression signature identified breast and bladder cancer as the most sensitive to TLT while glioblastoma multiforme as least sensitive.ConclusionsOur study identified TLT, a previously uncharacterized trisulfated sterol, as a potential therapeutic selective against BL-CL. Our results also showed that inhibition of AMPK and/or CHK1 might be an effective therapy in BL-CL.

scholarly journals Prognostic gene expression signature for high-grade serous ovarian cancer

2020 ◽  
Vol 31 (9) ◽  
pp. 1240-1250 ◽  
Author(s):  
J. Millstein ◽  
T. Budden ◽  
E.L. Goode ◽  
M.S. Anglesio ◽  
A. Talhouk ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ovarian Cancer ◽  
Gene Expression Signature ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Expression Signature ◽  
Prognostic Gene

scholarly journals A Gene-Expression Signature as a Predictor of Survival in Breast Cancer

2002 ◽  
Vol 347 (25) ◽  
pp. 1999-2009 ◽  
Author(s):  
Marc J. van de Vijver ◽  
Yudong D. He ◽  
Laura J. van 't Veer ◽  
Hongyue Dai ◽  
Augustinus A.M. Hart ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Gene Expression Signature ◽  
Expression Signature
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