The response to neoadjuvant chemoradiotherapy with 5-fluorouracil in locally advanced rectal cancer patients: a predictive proteomic signature

Chauvin, Anaïs; Wang, Chang-Shu; Geha, Sameh; Garde-Granger, Perrine; Mathieu, A; Lacasse, Vincent; Boisvert, François-Michel

doi:10.1186/s12014-018-9192-2

Cited by 38 publications

(44 citation statements)

References 56 publications

(57 reference statements)

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“…Moreover, CALD1 encodes the caldesmon protein, which is a calmodulin-binding and cytoskeleton-associated protein and regulates cell motility, such as migration and invasion (40,41). It has been suggested that CALD1 may indicate a general splicing event associated with cancer (41,42) and was also identified as a potential prognostic molecular marker for bladder and colon cancer (43)(44)(45).…”

Section: Discussionmentioning

confidence: 99%

A signature of tumor immune microenvironment genes associated with the prognosis of non‑small cell lung cancer

Zhang

et al. 2020

Oncol Rep

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Establishing a prognostic genetic signature closely related to the tumor immune microenvironment (TIME) to predict clinical outcomes is necessary. Using the Gene Expression Omnibus (GEO) database of a non-small cell lung cancer (NSCLC) cohort and the immune score derived from the Estimation of Stromal and Immune cells in Malignant Tumours using Expression data (ESTIMATE) algorithm, we applied the least absolute shrinkage and selection operator (LASSO) Cox regression model to screen a 10-gene signature among the 448 differentially expressed genes and found that the risk prediction models constructed by 10 genes could be more sensitive to prognosis than TNM (Tumor, Lymph node and Metastasis) stage (P=0.006). The CIBERSORT method was applied to quantify the relative levels of different immune cell types. It was found that the ratio of eosinophils, mast cells (MCs) resting and CD4 T cells memory activated in the low-risk group was higher than that in the high-risk group, and the difference was statistically significant (P= 0.003, P= 0.014 and P= 0.018, respectively). Inconsistently, the ratio of resting natural killer (NK) cells and activated plasma cells in the low-risk group was significantly lower than that in the high-risk group (P= 0.05 and P=0.009, respectively). Kaplan-Meier survival results showed that patients of the high-risk group had significantly shorter overall survival (OS) than those of the low-risk group in the training set (P<0.001). Furthermore, Kaplan-Meier survival showed that patients of the high-risk group had significantly shorter OS than those of the low-risk group (P=0.0025 and P=0.0157, respectively) in the validation set [GSE31210 and TCGA (The Cancer Genome Atlas)]. The 10-gene signature was found to be an independent risk factor for prognosis in univariate and multivariate Cox proportional hazard regression analyses (P<0.001). In addition, it was found that the risk model constructed by the 10-gene signature was related to the clinical related factors in logistic regression analysis. The genetic signature closely related to the immune microenvironment was found to be able to predict differences in the proportion of immune cells (eosinophils, resting MCs, memory activated CD4 T cells, resting NK cells and plasma cells) in the risk model. Our findings suggest that the genetic signature closely related to TIME could predict the prognosis of NSCLC patients, and provide some reference for immunotherapy.

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Section: Discussionmentioning

confidence: 99%

A signature of tumor immune microenvironment genes associated with the prognosis of non‑small cell lung cancer

Zhang

et al. 2020

Oncol Rep

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“…Previous mass spectrometric proteomic studies that have analyzed the proteome of cancer patients receiving radiotherapy have to a large extent focused on attempts to identify proteins that could be used as biomarkers to guide the use of radiotherapy by predicting patient response [10,11]. Several studies involving the proteomic profiling of rectal cancer patients have also identified proteins implicated in resistance to radiotherapy, such as acid ceramidase, or protein signatures predictive of radiotherapy response [12][13][14][15][16]. However, there is a paucity of studies with focus on investigating the overall effects of radiotherapy on plasma protein expression in rectal cancer patients.…”

Section: Introductionmentioning

confidence: 99%

Preoperative Radiotherapy Leads to Significant Differences in the Plasma Protein Profile of Rectal Cancer Patients

et al. 2020

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Introduction: Colorectal cancer (CRC) is the third most common cancer worldwide, accounting for 10% of the global cancer burden. Rectal cancer accounts for around 30% of CRC cases, and patients with resectable rectal cancer are often given preoperative radiotherapy (PRT) to reduce the rate of local recurrence. The human plasma proteome is an exceptionally complex proteome and ideal to study due to its ability to reflect the presence of diseases such as cancer and the ease of obtaining blood samples. Previous proteomic studies involving rectal cancer patients have mostly focused on the identification of proteins involved in resistance to radiotherapy. Objective: The aim of this study was to investigate the overall effects of PRT on plasma protein expression in rectal cancer patients, as there is a lack of such studies. Methods: Here, we have used mass spectrometry and sub-sequent statistical analyses to analyze the plasma samples of 30 rectal cancer patients according to PRT status (positive or negative) and tumor stage (II or III). Results and Conclusions:We discovered 42 proteins whose levels differed significantly between stage II and III rectal cancer patients who did or did not receive PRT. This study shows that PRT, although localized to the pelvis, leads to measurable, tumor stage-specific changes in plasma protein expression. Future studies of plasma proteins should, when relevant, take this into account and be aware of the widespread effects that PRT has on the plasma proteome.

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“…Patients with lung adenocarcinoma who have up-regulated ACTA2 expression are more likely to develop distant metastasis and have detrimental prognosis [32]. Besides, the expression level of CALD1 is higher in patients with rectal cancer who do not respond to the neoadjuvant radiochemotherapy [33]. Blockade of MYL9 function is a critical factor for reducing the matrix-remodelling and invasion-promoting abilities of cancer-associated broblasts [34].…”

Section: Discussionmentioning

confidence: 99%

Identification of Hub Genes to Control Cancer Stem cell Characteristics in Colon Adenocarcinoma Through Bioinformatics Analysis and Validation by Western Blotting

Liu

Zhang

Teng

et al. 2020

Preprint

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Background: Cancer stem cells (CSCs) are involved in the development of cancer. This study aimed to identify hallmark genes associated with the adjustment of CSC properties.Methods: The COAD data from The Cancer Genome Atlas(TCGA) database were assessed based on the mRNA stemness index (mRNAsi) and corrected mRNAsi. Then, both of them were analyzed with differentially expressed genes (DEGs). The gene modules were pinpointed through weighted gene co-expression network analysis (WGCNA). The genes of the most interest module were functionally annotated through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The Search Tool for the Retrieval of Interacting Genes (STRING) was adopted to obtain protein-protein interaction (PPI) networks, and the hub genes were identified in the light of the Molecular Complex Detection (MCODE) and Cytoscape plugin cytoHubba. Upstream genes were analyzed via the DisNor. In addition, the associations between clinical variables and hub genes were estimated. The bioinformatic results were verified based on Gene Expression Profling Integrative Analysis (GEPIA), Oncomine and Gene Expression Omnibus (GEO). Finally, the protein expression of the hub genes was verified by western blotting.Results: Both the corrected mRNAsi and mRNAsi increased within COAD tissues relative to those within normal colon tissues, which showed a significantly decreasing trend in COAD as the clinical stage. GO indicated the biological processes, including muscle cell differentiation, multicellular organismal signaling, muscle system process and muscle contraction. KEGG revealed Tight junction, Dilated cardiomyopathy (DCM), Vascular smooth muscle contraction, and the cGMP PKG signal transduction pathway. The seven hub genes (ACTA2, CALD1, LMOD1, MYL9, MYLK, TAGLN and TPM2) were identified in the brown module. Most of them were associated with clinical stage; MYL9, TAGLN and TPM2 were associated with overall survival. TGFB1, SRF, ROCK1 and PRKCA were the upstream genes through the DisNor. In the Oncomine, GEO and GEPIA databases, the expression of seven hub genes were down-regulated. In TCGA and GEPIA databases, the tendency of the seven hub genes was decreased with the advance in stage. Conclusions: The hub genes identified in the present study meight play a vital role in the preservation of COAD stem cells.

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The response to neoadjuvant chemoradiotherapy with 5-fluorouracil in locally advanced rectal cancer patients: a predictive proteomic signature

Cited by 38 publications

References 56 publications

A signature of tumor immune microenvironment genes associated with the prognosis of non‑small cell lung cancer

A signature of tumor immune microenvironment genes associated with the prognosis of non‑small cell lung cancer

Preoperative Radiotherapy Leads to Significant Differences in the Plasma Protein Profile of Rectal Cancer Patients

Identification of Hub Genes to Control Cancer Stem cell Characteristics in Colon Adenocarcinoma Through Bioinformatics Analysis and Validation by Western Blotting

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