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Expression of the Hippo transducer TAZ in association with WNT pathway mutations impacts survival outcomes in advanced gastric cancer patients treated with first-line chemotherapy

Overview of attention for article published in Journal of Translational Medicine, February 2018
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Title
Expression of the Hippo transducer TAZ in association with WNT pathway mutations impacts survival outcomes in advanced gastric cancer patients treated with first-line chemotherapy
Published in
Journal of Translational Medicine, February 2018
DOI 10.1186/s12967-018-1385-y
Pubmed ID
Authors

Elisa Melucci, Beatrice Casini, Livia Ronchetti, Laura Pizzuti, Francesca Sperati, Matteo Pallocca, Francesca De Nicola, Frauke Goeman, Enzo Gallo, Carla Azzurra Amoreo, Domenico Sergi, Irene Terrenato, Patrizia Vici, Luigi Di Lauro, Maria Grazia Diodoro, Edoardo Pescarmona, Maddalena Barba, Marco Mazzotta, Marcella Mottolese, Maurizio Fanciulli, Gennaro Ciliberto, Ruggero De Maria, Simonetta Buglioni, Marcello Maugeri-Saccà

Abstract

An extensive crosstalk co-regulates the Hippo and Wnt pathway. Preclinical studies revealed that the Hippo transducers YAP/TAZ mediate a number of oncogenic functions in gastric cancer (GC). Moreover, comprehensive characterization of GC demonstrated that the Wnt pathway is targeted by oncogenic mutations. On this ground, we hypothesized that YAP/TAZ- and Wnt-related biomarkers may predict clinical outcomes in GC patients treated with chemotherapy. In the present study, we included 86 patients with advanced GC treated with first-line chemotherapy in prospective phase II trials or in routine clinical practice. Tissue samples were immunostained to evaluate the expression of YAP/TAZ. Mutational status of key Wnt pathway genes (CTNNB1, APC and FBXW7) was assessed by targeted DNA next-generation sequencing (NGS). Survival curves were estimated and compared by the Kaplan-Meier product-limit method and the log-rank test, respectively. Variables potentially affecting progression-free survival (PFS) were verified in univariate Cox proportional hazard models. The final multivariate Cox models were obtained with variables testing significant at the univariate analysis, and by adjusting for all plausible predictors of the outcome of interest (PFS). We observed a significant association between TAZ expression and Wnt mutations (Chi-squared p = 0.008). Combined TAZ expression and Wnt mutations (TAZpos/WNTmut) was more frequently observed in patients with the shortest progression-free survival (negative outliers) (Fisher p = 0.021). Uni-and multivariate Cox regression analyses revealed that patients whose tumors harbored the TAZpos/WNTmut signature had an increased risk of disease progression (univariate Cox: HR 2.27, 95% CI 1.27-4.05, p = 0.006; multivariate Cox: HR 2.73, 95% CI 1.41-5.29, p = 0.003). Finally, the TAZpos/WNTmut signature negatively impacted overall survival. Collectively, our findings indicate that the oncogenic YAP/TAZ-Wnt crosstalk may be active in GC, conferring chemoresistant traits that translate into adverse survival outcomes.

Twitter Demographics

The data shown below were collected from the profiles of 2 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 13 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 13 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 5 38%
Student > Master 3 23%
Student > Bachelor 1 8%
Professor > Associate Professor 1 8%
Other 1 8%
Other 0 0%
Unknown 2 15%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 7 54%
Engineering 2 15%
Computer Science 1 8%
Medicine and Dentistry 1 8%
Unspecified 1 8%
Other 0 0%
Unknown 1 8%

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 07 March 2018.
All research outputs
#7,279,280
of 12,612,351 outputs
Outputs from Journal of Translational Medicine
#1,109
of 2,480 outputs
Outputs of similar age
#166,605
of 343,703 outputs
Outputs of similar age from Journal of Translational Medicine
#2
of 2 outputs
Altmetric has tracked 12,612,351 research outputs across all sources so far. This one is in the 40th percentile – i.e., 40% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,480 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.2. This one is in the 47th percentile – i.e., 47% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 343,703 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 48th percentile – i.e., 48% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 2 others from the same source and published within six weeks on either side of this one.