Reduced genomic tumor heterogeneity after neoadjuvant chemotherapy is related to favorable outcome in patients with esophageal adenocarcinoma

Obulkasim, Askar; Ylstra, Bauke; Essen, Hendrik F. van; Benner, Christian; Stenning, Sally; Langley, Ruth E.; Allum, William; Cunningham, David; Inam, Imran; Hewitt, Lindsay C; West, Nicolas P.; Meijer, Gerrit A.; Wiel, Mark A. van de; Grabsch, Heike

doi:10.18632/oncotarget.9857

Cited by 11 publications

(12 citation statements)

References 31 publications

(41 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The group that underwent surgery and neoadjuvant chemotherapy exhibited decreased heterogeneity. The study outcomes suggested that a decrease in heterogeneity may contribute to a survival benefit [47]. In the present study, we found that the heterogeneity decreased when cells were treated with the most effective drugs, and the heterogeneity either decreased slightly or increased when the least effective drugs were used (Figure 7B).…”

Section: Discussionsupporting

confidence: 62%

Microfluidic Single-Cell Proteomics Assay Chip: Lung Cancer Cell Line Case Study

et al. 2021

View full text Add to dashboard Cite

Cancer is a dynamic disease involving constant changes. With these changes, cancer cells become heterogeneous, resulting in varying sensitivity to chemotherapy. The heterogeneity of cancer cells plays a key role in chemotherapy resistance and cancer recurrence. Therefore, for effective treatment, cancer cells need to be analyzed at the single-cell level by monitoring various proteins and investigating their heterogeneity. We propose a microfluidic chip for a single-cell proteomics assay that is capable of analyzing complex cellular signaling systems to reveal the heterogeneity of cancer cells. The single-cell assay chip comprises (i) microchambers (n = 1376) for manipulating single cancer cells, (ii) micropumps for rapid single-cell lysis, and (iii) barcode immunosensors for detecting nine different secretory and intracellular proteins to reveal the correlation among cancer-related proteins. Using this chip, the single-cell proteomics of a lung cancer cell line, which may be easily masked in bulk analysis, were evaluated. By comparing changes in the level of protein secretion and heterogeneity in response to combinations of four anti-cancer drugs, this study suggests a new method for selecting the best combination of anti-cancer drugs. Subsequent preclinical and clinical trials should enable this platform to become applicable for patient-customized therapies.

show abstract

Section: Discussionsupporting

confidence: 62%

Microfluidic Single-Cell Proteomics Assay Chip: Lung Cancer Cell Line Case Study

et al. 2021

View full text Add to dashboard Cite

show abstract

“…[7][8][9] Conversely, patients with disease with little or no response to nCRT experience poorer outcomes and survival. Although high ITH is known to contribute to cytotoxic and targeted molecular therapy resistance in CRC, breast, esophageal, and lung cancers, 29,30 no studies to date have directly examined the relationship of rectal cancer tumor heterogeneity and response to nCRT. By stratifying the biologic profiles of locally advanced rectal cancer, providers could have the ability to discuss an individual patient's prognosis.…”

Section: Discussionmentioning

confidence: 99%

Tumor Heterogeneity as a Predictor of Response to Neoadjuvant Chemotherapy in Locally Advanced Rectal Cancer

Greenbaum

Martín

Bocklage

et al. 2019

Clinical Colorectal Cancer

View full text Add to dashboard Cite

A standard therapy for locally advanced cancers includes neoadjuvant chemoradiation; however, currently there is no way of knowing which patients have disease that will respond to such therapy. We analyzed 21 pretreatment rectal cancer biopsy samples and found a positive correlation of the response to therapy with a quantitative mutant-allele tumor heterogeneity (MATH) score. This next-generation sequencing derived score may serve as a biomarker for response to therapy. Background: Neoadjuvant chemoradiotherapy (nCRT) is the standard of care for locally advanced adenocarcinoma of the rectum, but it is currently unknown which patients have disease that will respond. This study tested the correlation between response to nCRT and intratumoral heterogeneity using next-generation sequencing assays. Patients and Methods: DNA was extracted from formalin-fixed, paraffin-embedded biopsy samples from a cohort of patients with locally advanced rectal adenocarcinoma (T3/4 or N1/2 disease) who received nCRT. High read-depth sequencing of > 400 cancer-relevant genes was performed. Tumor mutations and variant allele frequencies were used to calculate mutant-allele tumor heterogeneity (MATH) scores as measures of intratumoral heterogeneity. Response to nCRT was pathologically scored after surgical resection. Results: Biopsy samples from 21 patient tumors were analyzed. Eight patients had disease noted to have complete response, 2 moderate, 4 minimal, and 7 poor. Higher MATH scores correlated with poorer response to treatment, demonstrating significantly increased tumor heterogeneity compared to complete response (P ¼ .039). Conclusion: The application of MATH scores as a measure of tumor heterogeneity may provide a useful biomarker for treatment response in locally advanced rectal cancer.

show abstract

“…Of the remaining 46 studies, 25 were excluded using the exclusion criteria. In the end, 21 studies were included (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33). These studies contain 38 pieces of comparison information that were extracted.…”

Section: Resultsmentioning

confidence: 99%

“…Other researchers (20,22,24,25,28,31,33,35) directly use VAF to directly reflect the information of ITH through methods such as mutant-allele tumor heterogeneity (MATH). Copy number variations (CNVs), as genetic information with high mutation frequency, have also been recently used by a few researchers in the evaluation of ITH (26,29). Table 1 summarizes the details.…”

Section: Different Ith Assessment Methods Had Limited Influence On This Studymentioning

confidence: 99%

Intratumor Heterogeneity as a Prognostic Factor in Solid Tumors: A Systematic Review and Meta-Analysis

Gào

Zheng

et al. 2021

Front. Oncol.

View full text Add to dashboard Cite

BackgroundThe landscape of intratumor heterogeneity (ITH) is present from the tumor evolution. ITH is a promising clinical indicator, but the association between ITH and prognosis remains controversial. Therefore, a meta-analysis was performed to explore whether ITH can serve as a valuable prognostic indicator in solid tumors.MethodsAll included studies were from PubMed, Embase, Cochrane, and Web of Science databases up to October 10, 2020. Studies based on ITH with available prognostic information were included. Three researchers independently completed study selection and data extraction following PRISMA guidelines. The random-effect model was used for synthesis. Hazard ratio (HR) and 95% confidence intervals (CI) were used with the endpoint defined by overall survival (OS), disease-specific survival (DFS), and progression-free survival (PFS).ResultsA total of 9,804 solid tumor patients from 21 studies were included. Analysis of specific cancers in the TCGA database showed similar results based on different ITH assessment methods, which provided the logical support for data consolidation. Available evidence revealed a negative relationship between ITH and prognosis for a specific cancer (such as lung cancer). However, the OS results from 14 tumor types showed that high ITH associated with shorter survival time [HR 1.65 (95% CI, 1.42–1.91)]. PFS and DFS analyses showed similar results [HR 1.89 (95% CI, 1.41–2.54) and HR 1.87 (95% CI, 1.15–3.04)] in general. The status of tumor metastasis and sampling models were not the confounding factors.ConclusionsHigh ITH is associated with worse prognosis in many solid tumors in general although this association was absent for some cancers. ITH is expected to be a promising clinical prognostic factor for the improvement of assessment, treatment, and surveillance strategy.

show abstract

Reduced genomic tumor heterogeneity after neoadjuvant chemotherapy is related to favorable outcome in patients with esophageal adenocarcinoma

Cited by 11 publications

References 31 publications

Microfluidic Single-Cell Proteomics Assay Chip: Lung Cancer Cell Line Case Study

Microfluidic Single-Cell Proteomics Assay Chip: Lung Cancer Cell Line Case Study

Tumor Heterogeneity as a Predictor of Response to Neoadjuvant Chemotherapy in Locally Advanced Rectal Cancer

Intratumor Heterogeneity as a Prognostic Factor in Solid Tumors: A Systematic Review and Meta-Analysis

Contact Info

Product

Resources

About