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Serum Proteome Profiling Identifies Early Markers of Therapeutic Response to Neoadjuvant Chemotherapy of Breast Cancer

ABSTRACT: We performed a proteomic serum profiling of patients with non-metastasized breast cancer (BC) who received neoadjuvant chemotherapy (NACT). Samples were collected at three timepoints during NACT. Furthermore, we compared serum samples of BC patients pre-NACT to a control group of healthy volunteers.

PROVIDER: EGAS00001006228 | EGA |

REPOSITORIES: EGA

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Serum Proteome Profiling Identifies Early Markers of Therapeutic Response to Neoadjuvant Chemotherapy of Breast Cancer

Project description:We performed a proteomic serum profiling of patients with non-metastasized breast cancer (BC) who received neoadjuvant chemotherapy (NACT). Samples were collected at three timepoints during NACT. Furthermore, we compared serum samples of BC patients pre-NACT to a control group of healthy volunteers.

| EGAD00010002330 | EGA

DNA methylation markers panel can improve prediction of response to neoadjuvant chemotherapy in luminal B breast cancer

Project description:Despite the advantages of neoadjuvant chemotherapy (NACT), associated toxicity is a serious complication that renders monitoring of the patients response to NACT highly important. Thus, prediction of tumor response to treatment is imperative to avoid exposure of potential non-responders to deleterious complications. We have performed genome-wide analysis of DNA methylation by XmaI-RRBS and selected CpG dinucleotides differential methylation of which discriminates luminal B breast cancer samples with different sensitivity to NACT. With this data, we have developed multiplex methylation sensitive restriction enzyme PCR (MSRE-PCR) protocol for determining the methylation status of 10 genes (SLC9A3, C1QL2, DPYS, IRF4, ADCY8, KCNQ2, TERT, SYNDIG1, SKOR2 and GRIK1) that distinguish BC samples with different NACT response. Analysis of these 10 markers by MSRE-PCR in biopsy samples allowed us to reveal three top informative combinations of markers, (1) IRF4 and C1QL2; (2) IRF4, C1QL2, and ADCY8; (3) IRF4, C1QL2, and DPYS, with the areas under ROC curves (AUCs) of 0.75, 0.78 and 0.74, respectively. A classifier based on IRF4 and C1QL2 better meets the diagnostic panel simplicity requirements, as it consists of only two markers. Diagnostic accuracy of the panel of these two markers is 0.75, with the sensitivity of 75% and specificity of 75%.

2020-01-25 | GSE144221 | GEO

Integrated proteomics and phosphoproteomics revealed druggable kinases in neoadjuvant chemotherapy resistant tongue cancer

Project description:Tongue squamous cell carcinoma is characterised by poor prognosis and high metastatic events. Patients with unresectable tumors are benefiting from neoadjuvant chemotherapy (NACT) which surgical resection, and controls distant metastasis, and locoregional recurrence. However, resistance to NACT limit the success of the treatment regimen. In this study, we investigated the altered proteome and phosphoproteome of NACT resistant and sensitive cohort using Mass spectrometry-based proteomics. We carried out proteomic as well as phosphoproteomic analysis of treatment naïve tongue cancer patients whose response to NACT is recorded. Proteomic analysis revealed distinct protein expression between the responders and non-responders. The Phosphoproteomic analysis revealed kinases and the pathways associated with NACT resistance in tongue cancer.

2023-03-11 | PXD037356 | Pride

Proteomic Alterations Associated with Residual Disease in Neoadjuvant Chemotherapy Treated Ovarian Cancer Tissues

Project description:Optimal cytoreduction to no residual disease (R0) correlates with improved disease outcome in the management of high-grade serous ovarian cancer (HGSOC) patients. Neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) offers an alternate approach to management of HGSOC patients to achieve complete resection. This study assessed proteomic alterations in matched, chemotherapy naïve and NACT-treated patients tumors obtained from HGSOC patients with suboptimal (R1) versus optimal (R0) debulking at IDS. We describe distinct proteome profiles in pre- and post-NACT HGSOC tumors correlating with residual disease status providing prognostic biomarkers for residual disease at IDS as well as candidate proteins associated with NACT resistance warranting further pre-clinical investigation.

2022-10-05 | PXD031929 | Pride

Molecular Response to Neoadjuvant Chemotherapy in High-Grade Serous Ovarian Carcinoma

Project description:While high-grade serous ovarian carcinoma (HGSOC) is the most common histological subtype of ovarian cancer, significant tumor heterogeneity exists. In addition, chemotherapy induces changes in gene expression and alters the mutational profile. To evaluate the notion that patients with HGSOC could be better classified for optimal treatment based on gene expression, we compared genetic variants (by DNA next-generation sequencing [NGS] using a 50 gene Ion Torrent panel) and gene expression (using the NanoString® PanCancer 770 gene Panel) in the tumor from 20 patients with HGSOC before and after neoadjuvant chemotherapy (NACT). NGS was performed on plasma cell free DNA (cfDNA) on a select group of patients (n=14) in order to assess the utility of using cfDNA to monitor these changes. A total of 86 genes had significant changes in RNA expression after NACT. Thirty-eight genetic variants (including SNPs) from 6 genes were identified in tumors pre-NACT, while 59 variants from 19 genes were detected in the cfDNA. The number of DNA variants were similar after NACT. Of the 59 variants in the plasma pre-NACT, only 6 persisted; whereas 33 of 38 specific variants in the tumor DNA remained unchanged. Pathway analysis showed the most significant alterations in the cell cycle and DNA damage pathways.

2018-02-01 | GSE109934 | GEO

Project description:We explore the potential of immune-associated expression profiles in a series of Epithelial Ovarian Cancer (EOC) patients undergoing neoadjuvant chemotherapy (NACT), comparing primary lesions before patients underwent carboplatin/paclitaxel-based NACT (so-called ´biopsy samples´) and interval debulking surgery (IDS) samples from residual lesions after treatment with chemotherapy (so-called ´surgery samples´).

2022-01-27 | GSE181597 | GEO

Genome-wide expression profiling of mediastinal lymph nodal metastasis of stage IIIA NSCLC patients before neoadjuvant chemotherapy

Project description:Non–small-cell lung cancer (NSCLC) is the leading cause of cancer deaths worldwide due to late diagnosis and lack of effective therapies to treat metastatic disease. About one third of NSCLC patients present at diagnosis with locally advanced cancer (stage IIIA) which metastasizes ipsilateral mediastinal or subcarinal lymph nodes (N2). Neoadjuvant chemotherapy (NACT) followed by surgery is the treatment of choice for resectable N2 disease. However, the majority of patients do not respond to NACT and show persistent lymph nodal metastases and an adverse outcome. Our scant knowledge of the molecular biology of lymph node metastases (LNmets) represents a major obstacle to develop more effective therapies. Here, we investigated gene expression profile (coding and non-coding) of LNmets collected by endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) and mediastinoscopy, in two cohorts of stage IIIA patients before NACT (N=70). We discovered a microRNA expression signature in LNmets predictive of NACT response of N2 patients. Importantly, we unveiled a miR-455-5p/PD-L1 regulatory axis which drives chemotherapy resistance and impact T cell viability in NSCLC. Our data suggests the relevance of LNmets molecular profiling to predict response to NACT likewise presents strong evidences of a miRNA-based mechanism which functionally links chemotherapy response with PD-L1 regulation.

2022-12-31 | GSE193707 | GEO

An immunological signature to predict outcome in patients with triple-negative breast cancer patients with residual disease after neoadjuvant chemotherapy

Project description:When triple-negative breast cancer (TNBC) patients have residual disease after neoadjuvant chemotherapy (NACT), they have a high risk of metastatic relapse. With immune infiltrate in TNBC being prognostic and predictive of response to treatment, our aim was to develop an immunologic transcriptomic signature using post NACT samples to predict relapse.

2022-09-20 | GSE185507 | GEO

Neoadjuvant chemotherapy modulates T cell responses in high-grade serous ovarian cancer metastases

Project description:Our data suggest that neoadjuvant chemotherapy enhances anti-cancer responses of T cells in peritoneal metastases of patients with high-grade serous ovarian cancer but does not decrease levels of immune checkpoint molecules, providing a rationale for sequential chemo-immunotherapy. tRNA was isolated from 35 omental tissue samples of HGSOC metastases either pre or post NACT treatment. RNASeq was performed on poly-A selected mRNA fragments, 100 b.p paired end, and strand specific, on average 40 million reads per sample.

2016-07-27 | E-GEOD-71340 | biostudies-arrayexpress

The impact of neoadjuvant chemotherapy on tumor microenvironment in advanced high-grade serous carcinoma

Project description:High-grade serous ovarian, fallopian tube or peritoneal carcinoma is an aggressive subtype that frequently develops resistance to chemotherapy. It remains controversial whether the resistance is caused by the acquisition of new molecular aberrations or alternatively through the selection of rare preexisting tumor clones. To address this question, we applied single cell RNA sequencing to depict the tumor landscape of a single case of advanced high-grade serous fallopian tube carcinoma during neoadjuvant chemotherapy (NACT).

2022-08-16 | GSE191301 | GEO

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