Dataset Information

CD44v6 High Membranous Expression Is a Predictive Marker of Therapy Response in Gastric Cancer Patients.

ABSTRACT: In gastric cancer (GC), biomarkers that define prognosis and predict treatment response remain scarce. We hypothesized that the extent of CD44v6 membranous tumor expression could predict prognosis and therapy response in GC patients. Two GC surgical cohorts, from Portugal and South Korea (n = 964), were characterized for the extension of CD44v6 membranous immuno-expression, clinicopathological features, patient survival, and therapy response. The value of CD44v6 expression in predicting response to treatment and its impact on prognosis was determined. High CD44v6 expression was associated with invasive features (perineural invasion and depth of invasion) in both cohorts and with worse survival in the Portuguese GC cohort (HR 1.461; 95% confidence interval 1.002-2.131). Patients with high CD44v6 tumor expression benefited from conventional chemotherapy in addition to surgery (p < 0.05), particularly those with heterogeneous CD44v6-positive and -negative populations (CD44v6_3+) (p < 0.007 and p < 0.009). Our study is the first to identify CD44v6 high membranous expression as a potential predictive marker of response to conventional treatment, but it does not clarify CD44v6 prognostic value in GC. Importantly, our data support selection of GC patients with high CD44v6-expressing tumors for conventional chemotherapy in addition to surgery. These findings will allow better stratification of GC patients for treatment, potentially improving their overall survival.

SUBMITTER: Almeida GM

PROVIDER: S-EPMC8465138 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

CD44v6 High Membranous Expression Is a Predictive Marker of Therapy Response in Gastric Cancer Patients.

Almeida Gabriela M GM Pereira Carla C Park Ji-Hyeon JH Lemos Carolina C Campelos Sofia S Gullo Irene I Martins Diana D Gonçalves Gilza G Leitão Dina D Neto João Luís JL André Ana A Borges Clara C Almeida Daniela D Lee Hyuk-Joon HJ Kong Seong-Ho SH Kim Woo Ho WH Carneiro Fátima F Almeida Raquel R Yang Han-Kwang HK Oliveira Carla C

Biomedicines 20210918 9

In gastric cancer (GC), biomarkers that define prognosis and predict treatment response remain scarce. We hypothesized that the extent of CD44v6 membranous tumor expression could predict prognosis and therapy response in GC patients. Two GC surgical cohorts, from Portugal and South Korea (<i>n</i> = 964), were characterized for the extension of CD44v6 membranous immuno-expression, clinicopathological features, patient survival, and therapy response. The value of CD44v6 expression in predicting r ...[more]

PMID: 34572441

Similar Datasets

Project description:BackgroundEstablished genetic biomarkers in chronic lymphocytic leukemia (CLL) have been useful in predicting response to chemoimmunotherapy but are less predictive of response to targeted therapies. With several such targeted therapies now approved for CLL, identifying novel, non-genetic predictive biomarkers of response may help to select the optimal therapy for individual patients.MethodsWe coupled data from a functional precision medicine technique called BH3-profiling, which assesses cellular cytochrome c loss levels as indicators for survival dependence on anti-apoptotic proteins, with multi-omics data consisting of targeted and whole-exome sequencing, genome-wide DNA methylation profiles, RNA-sequencing, protein and functional analyses, to identify biomarkers for treatment response in CLL patients.ResultsWe initially studied 73 CLL patients from a discovery cohort. We found that greater dependence on the anti-apoptotic BCL-2 protein was associated with prognostically favorable genetic biomarkers. Furthermore, BCL-2 dependence was strongly associated with gene expression patterns and signaling pathways that suggest a more targeted drug-sensitive milieu and was predictive of drug responses. We subsequently demonstrated that these associations were causal in cell lines and additional CLL patient samples. To validate the findings from our discovery cohort and in vitro studies, we utilized primary CLL cells from 54 additional patients treated on a prospective, phase-2 clinical trial of the BTK inhibitor ibrutinib given in combination with chemoimmunotherapy (fludarabine, cyclophosphamide, rituximab) and confirmed in this independent dataset that higher BCL-2 dependence predicted favorable clinical response, independent of the genetic background of the CLL cells.ConclusionWe comprehensively defined BCL-2 dependence as a potential functional and predictive biomarker of treatment response in CLL, underscoring the importance of characterizing apoptotic signaling in CLL to stratify patients beyond genetic markers and identifying novel combinations to exploit BCL-2 dependence therapeutically. Our approach has the potential to help optimize targeted therapy combinations for CLL patients.

Dataset Information

CD44v6 High Membranous Expression Is a Predictive Marker of Therapy Response in Gastric Cancer Patients.

Publications

CD44v6 High Membranous Expression Is a Predictive Marker of Therapy Response in Gastric Cancer Patients.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets