A compact VEGF signature associated with distant metastases and poor outcomes

Hu, Zhiyuan; Fan, Cheng; Livasy, Chad; He, Xiaping; Oh, Daniel S.; Ewend, Matthew G.; Carey, Lisa A.; Subramanian, Subbaya; West, Robert B.; Ikpatt, Francis; Olopade, Olufunmilayo I.; Rijn, Matt van de; Perou, Charles M.

doi:10.1186/1741-7015-7-9

Cited by 162 publications

(178 citation statements)

References 62 publications

Supporting

Mentioning

174

Contrasting

Order By: Relevance

“…transcriptional hypoxia signature, containing SLC16A3, was associated with distant metastasis and poor clinical outcome in breast, lung and brain cancers (glioblastoma); 33 however, they did not distinguish between stromal or tumor cell expression of this signature.…”

Section: -30mentioning

confidence: 99%

Evidence for a stromal-epithelial “lactate shuttle” in human tumors

et al. 2011

View full text Add to dashboard Cite

Section: -30mentioning

confidence: 99%

Evidence for a stromal-epithelial “lactate shuttle” in human tumors

et al. 2011

View full text Add to dashboard Cite

“…Several hypoxia signatures have been constructed in different tissues (10)(11)(12)(13)(14)(15)(16)(17)(18), but a common cancer signature seems difficult to derive (19). The only hypoxia signature presented for cervical cancer was discovered in our previous work by combining global gene expression profiles and dynamic contrast enhanced (DCE)-MRI of the same patients (20).…”

Section: Introductionmentioning

confidence: 99%

Integrative Analysis of DCE-MRI and Gene Expression Profiles in Construction of a Gene Classifier for Assessment of Hypoxia-Related Risk of Chemoradiotherapy Failure in Cervical Cancer

Fjeldbo

Julin

Lando

et al. 2016

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: A 31-gene expression signature reflected in dynamic contrast enhanced (DCE)-MR images and correlated with hypoxia-related aggressiveness in cervical cancer was identified in previous work. We here aimed to construct a dichotomous classifier with key signature genes and a predefined classification threshold that separated cervical cancer patients into a more and less hypoxic group with different outcome to chemoradiotherapy.Experimental Design: A training cohort of 42 patients and two independent cohorts of 108 and 131 patients were included. Gene expression data were generated from tumor biopsies by two Illumina array generations (WG-6, HT-12). Technical transfer of the classifier to a reverse transcription quantitative PCR (RT-qPCR) platform was performed for 74 patients. The amplitude A Brix in the Brix pharmacokinetic model was extracted from DCE-MR images of 64 patients and used as an indicator of hypoxia.Results: Classifier candidates were constructed by integrative analysis of A Brix and gene expression profiles in the training cohort and evaluated by a leave-one-out cross-validation approach. On the basis of their ability to separate patients correctly according to hypoxia status, a 6-gene classifier was identified. The classifier separated the patients into two groups with different progression-free survival probability. The robustness of the classifier was demonstrated by successful validation of hypoxia association and prognostic value across cohorts, array generations, and assay platforms. The prognostic value was independent of existing clinical markers, regardless of clinical endpoints.Conclusions: A robust DCE-MRI-associated gene classifier has been constructed that may be used to achieve an early indication of patients' risk of hypoxia-related chemoradiotherapy failure.

show abstract

“…A 120-gene Nanostring nCounter codeset was designed from previously reported gene sets predictive of BRAF mutation status and cetuximab response in mCRC [13,17,37], and a hypoxia signature predictive of metastasis in a broad range of tumor types [38]. Additional genes of interest such as RAD51, EGFR, ERBB2, and CRYAB were also included [35,[39][40][41][42].…”

Section: Gene Expression Profiles Gene Selection and Probe Designmentioning

confidence: 99%

Genomic markers of panitumumab resistance including ERBB2/HER2 in a phase II study of KRAS wild-type (wt) metastatic colorectal cancer (mCRC).

Barry¹,

Li-Chang²,

Kennecke³

2015

JCO

View full text Add to dashboard Cite

A prospective study was conducted to identify biomarkers associated with resistance to panitumumab monotherapy in patients with metastatic colorectal cancer (mCRC). Patients with previously treated, codon 12/13 KRAS wt, mCRC were prospectively administered panitumumab 6mg/kg IV q2weeks. Of 34 panitumumabtreated patients, 11 (32%) had progressive disease at 8 weeks and were classified as non-responders.A Nanostring nCounter-based assay identified a 5-gene expression signature (ERBB2, MLPH, IRX3, MYRF, and KLK6) associated with panitumumab resistance (P = 0.001). Immunohistochemistry and in situ hybridization determined that the HER2 (ERBB2) protein was overexpressed in 4/11 non-responding and 0/21 responding cases (P = 0.035). Two non-responding tumors had ERBB2 gene amplification only, and one demonstrated both ERBB2 amplification and mutation. A non-codon 12/13 KRAS mutation occurred in one panitumumab-resistant patient and was mutually exclusive with ERBB2/HER2 abnormalities.This study identifies a 5-gene signature associated with non-response to single agent panitumumab, including a subgroup of non-responders with evidence of aberrant ERBB2/HER2 signaling. KRAS wt tumors resistant to EGFRi may be identified by gene signature analysis, and the HER2 pathway plays an important role in resistance to therapy.

show abstract

A compact VEGF signature associated with distant metastases and poor outcomes

Abstract: Background: Tumor metastases pose the greatest threat to a patient's survival, and thus, understanding the biology of disseminated cancer cells is critical for developing effective therapies.

Cited by 162 publications

References 62 publications

Evidence for a stromal-epithelial “lactate shuttle” in human tumors

Evidence for a stromal-epithelial “lactate shuttle” in human tumors

Integrative Analysis of DCE-MRI and Gene Expression Profiles in Construction of a Gene Classifier for Assessment of Hypoxia-Related Risk of Chemoradiotherapy Failure in Cervical Cancer

Genomic markers of panitumumab resistance including ERBB2/HER2 in a phase II study of KRAS wild-type (wt) metastatic colorectal cancer (mCRC).

Contact Info

Product

Resources

About