Serum biomarkers analyzed by LC-MS/MS as predictors for short outcome of non-small cell lung cancer patients treated with chemoradiotherapy

Huang, Weiqing; Ding, Xuanfeng; Li, B; Fan, Min; Sun, Hong-yi; Yi, Yan; Zhang, J

doi:10.4149/neo_2013_002

Cited by 9 publications

(10 citation statements)

References 25 publications

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“…As a result, only a few studies have examined the proteome associated with resistance of NSCLC to CDDP. 17,18 Experimental strategies have however been devised to circumvent the technical hurdle of global protein level analysis. For instance, the 'nascent translatome' is experimentally accessible by resolving cellular mRNA according to their translation rate.…”

Section: Reportmentioning

confidence: 99%

Translational regulation of the mRNA encoding the ubiquitin peptidase USP1 involved in the DNA damage response as a determinant of Cisplatin resistance

et al. 2016

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(2016) Cisplatin (cis-diaminedichloroplatin (II), CDDP) is part of the standard therapy for a number of solid tumors including Non-Small-Cell Lung Cancer (NSCLC). The initial response observed is in most cases only transient and tumors quickly become refractory to the drug. Tumor cell resistance to CDDP relies on multiple mechanisms, some of which still remain unknown. In search for such mechanisms, we examined the impact of CDDP on mRNA translation in a sensitive and in a matched resistant NSCLC cell line. We identified a set of genes whose mRNAs are differentially translated in CDDP resistant vs. sensitive cells. The translation of the mRNA encoding the Ubiquitin-Specific Peptidase 1 (USP1), a Ubiquitin peptidase with important function in multiple DNA repair pathways, is inhibited by CDDP exposure in the sensitive cells, but not in the resistant cells. This lack of down-regulation of USP1 expression at the translational level plays a primary role in CDDP resistance since inhibition of USP1 expression or activity by siRNA or the small molecule inhibitor ML323, respectively is sufficient to re-sensitize resistant cells to CDDP. We involved the USP1 mRNA translation as a major mechanism of CDDP resistance in NSCLC cells and suggest that USP1 could be evaluated as a candidate predictive marker and as a therapeutic target to overcome CDDP resistance. More generally, our results indicate that analysis of gene expression at the level of mRNA translation is a useful approach to identify new determinants of CDDP resistance.

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Section: Reportmentioning

confidence: 99%

Translational regulation of the mRNA encoding the ubiquitin peptidase USP1 involved in the DNA damage response as a determinant of Cisplatin resistance

et al. 2016

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Section: Systems Biology and Cisplatin Resistancementioning

confidence: 99%

“…262, 263 The latter approach allowed for the identification of α 1-antitripsin (a circulating protease inhibitor with anti-inflammatory functions) and S100A9 (a Ca 2+ -binding protein that exerts immunomodulatory effects) as possible biomarkers of clinical CDDP resistance. 262, 263 Moreover, CDDP resistance has been associated with immunopeptidomic alterations, that is, changes in the composition and abundance of peptides presented on the cell surface in complex with MHC molecules. 260 This is particularly important in view of the facts that (i) several anticancer regimens operate by eliciting or boosting anticancer immunity, some of them by altering the immunopeptidome of malignant cells 264, 265 and that (ii) CDDP is generally considered as a non-immunogenic anticancer agent.…”

Section: Systems Biology and Cisplatin Resistancementioning

confidence: 99%

Systems biology of cisplatin resistance: past, present and future

Vitale²,

et al. 2014

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The platinum derivative cis-diamminedichloroplatinum(II), best known as cisplatin, is currently employed for the clinical management of patients affected by testicular, ovarian, head and neck, colorectal, bladder and lung cancers. For a long time, the antineoplastic effects of cisplatin have been fully ascribed to its ability to generate unrepairable DNA lesions, hence inducing either a permanent proliferative arrest known as cellular senescence or the mitochondrial pathway of apoptosis. Accumulating evidence now suggests that the cytostatic and cytotoxic activity of cisplatin involves both a nuclear and a cytoplasmic component. Despite the unresolved issues regarding its mechanism of action, the administration of cisplatin is generally associated with high rates of clinical responses. However, in the vast majority of cases, malignant cells exposed to cisplatin activate a multipronged adaptive response that renders them less susceptible to the antiproliferative and cytotoxic effects of the drug, and eventually resume proliferation. Thus, a large fraction of cisplatin-treated patients is destined to experience therapeutic failure and tumor recurrence. Throughout the last four decades great efforts have been devoted to the characterization of the molecular mechanisms whereby neoplastic cells progressively lose their sensitivity to cisplatin. The advent of high-content and high-throughput screening technologies has accelerated the discovery of cell-intrinsic and cell-extrinsic pathways that may be targeted to prevent or reverse cisplatin resistance in cancer patients. Still, the multifactorial and redundant nature of this phenomenon poses a significant barrier against the identification of effective chemosensitization strategies. Here, we discuss recent systems biology studies aimed at deconvoluting the complex circuitries that underpin cisplatin resistance, and how their findings might drive the development of rational approaches to tackle this clinically relevant problem.

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“…The peptidome refers to the low-molecular-weight proteome of serum protein fragments and peptides and represents an emerging tool for biomarker discovery [ 8 – 10 ]. The content of serum peptides in the blood is relatively low, and the serum peptide which is related to the disease is even lower.…”

Section: Discussionmentioning

confidence: 99%

Study on the Diagnosis of Gastric Cancer by Magnetic Beads Extraction and Mass Spectrometry

Zhu

Xing

Cao

et al. 2020

BioMed Research International

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Objective. This study constructed a model for the early diagnosis of gastric cancer by comparing the serum peptides profiles of patients with advanced gastric cancer and healthy people. And that model may be the potential to be applied for the efficacy evaluation and recurrence monitoring in gastric cancer. Methods. Serums of 30 healthy people and 30 advanced gastric cancer patients were matched by age and gender were collected. The serum peptide spectrum was obtained by MB-WCX concentration and MALDI-TOF MS analysis. Based on the analysis of the efficiency of differential peptides in the diagnosis of gastric cancer, we first established a model for the diagnosis of gastric cancer based on differential peptides and then carried out external verification. The diagnostic reliability of this model was further tested by compared with carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9). Results. In this present study, we found the expression of two peptide peaks with a molecular weight of 2863 Da and 2953 Da were significantly increased in gastric cancer serum, while the expression of two peptide peaks with a molecular weight of 1945 Da and 2082 Da were significantly decreased. Depending on the characteristics of peptide expression, we constructed a diagnostic model, we compared the sensitivity and specificity of the model established by 2953 Da/1945 Da, and found this model is significantly higher than CEA and CA19-9. Conclusion. There were some differences in serum peptides profiles between patients with advanced gastric cancer and healthy people. The serum peptide diagnostic models based on 2953 Da and 1945 Da have high diagnostic efficiency for advanced gastric cancer. Our result indicated that this model was well worth further validation for clinical diagnosis.

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Serum biomarkers analyzed by LC-MS/MS as predictors for short outcome of non-small cell lung cancer patients treated with chemoradiotherapy

Cited by 9 publications

References 25 publications

Translational regulation of the mRNA encoding the ubiquitin peptidase USP1 involved in the DNA damage response as a determinant of Cisplatin resistance

Translational regulation of the mRNA encoding the ubiquitin peptidase USP1 involved in the DNA damage response as a determinant of Cisplatin resistance

Systems biology of cisplatin resistance: past, present and future

Study on the Diagnosis of Gastric Cancer by Magnetic Beads Extraction and Mass Spectrometry

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