Quantitative proteomics identifies brain acid soluble protein 1 (BASP1) as a prognostic biomarker candidate in pancreatic cancer tissue

Zhou, Qimin; Andersson, Roland; Hu, Dingyuan; Bauden, Monika; Kristl, Theresa; Sasor, Agata; Pawłowski, Krzysztof; Pla, Indira; Hilmersson, Katarzyna Said; Zhou, Mengtao; Liu, Fan; Markó-Varga, György; Ansari, Daniel

doi:10.1016/j.ebiom.2019.04.008

Cited by 46 publications

(34 citation statements)

References 56 publications

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“…The BASP1 gene is downregulated in most mammalian cancers, and tumor‐suppressive functions of BASP1 were observed in several human cancer models (Guo et al , ; Marsh et al , ; Zhang et al , ; Zhou et al , ; Zhou et al , ). This corroborates our original finding that BASP1 strongly interferes with v‐Myc‐induced oncogenicity and displays properties of a tumor suppressor (Hartl et al , ).…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, one of the WT1 targets is MYC , which is activated by WT1 but suppressed by a WT1 : BASP1 complex (Goodfellow et al , ; Green et al , ; Han et al , ; Wu et al , ). Recent studies showed that WT1 is activated in pancreatic cancer and that patients with elevated BASP1 levels have a significantly better prognosis than individuals whose cancer cells contain no BASP1 but high WT1 levels (Zhou et al , ).…”

Section: Discussionmentioning

confidence: 99%

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The brain acid‐soluble protein 1 (BASP1) interferes with the oncogenic capacity of MYC and its binding to calmodulin

et al. 2020

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The MYC protein is a transcription factor with oncogenic potential controlling fundamental cellular processes such as cell proliferation, metabolism, differentiation, and apoptosis. The MYC gene is a major cancer driver, and elevated MYC protein levels are a hallmark of most human cancers. We have previously shown that the brain acid‐soluble protein 1 gene (BASP1) is specifically downregulated by the v‐myc oncogene and that ectopic BASP1 expression inhibits v‐myc‐induced cell transformation. The 11‐amino acid effector domain of the BASP1 protein interacts with the calcium sensor calmodulin (CaM) and is mainly responsible for this inhibitory function. We also reported recently that CaM interacts with all MYC variant proteins and that ectopic CaM increases the transactivation and transformation potential of the v‐Myc protein. Here, we show that the presence of excess BASP1 or of a synthetic BASP1 effector domain peptide leads to displacement of v‐Myc from CaM. The protein stability of v‐Myc is decreased in cells co‐expressing v‐Myc and BASP1, which may account for the inhibition of v‐Myc. Furthermore, suppression of v‐Myc‐triggered transcriptional activation and cell transformation is compensated by ectopic CaM, suggesting that BASP1‐mediated withdrawal of CaM from v‐Myc is a crucial event in the inhibition. In view of the tumor‐suppressive role of BASP1 which was recently also reported for human cancer, small compounds or peptides based on the BASP1 effector domain could be used in drug development strategies aimed at tumors with high MYC expression.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The brain acid‐soluble protein 1 (BASP1) interferes with the oncogenic capacity of MYC and its binding to calmodulin

et al. 2020

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“…Sample processing and LC-MS/MS analysis were performed as reported previously [10]. Briefly, proteins extracted from fresh frozen pancreas specimens were reduced, alkylated and digested into peptides using Lys-C and trypsin.…”

Section: Ms-based Proteomicsmentioning

confidence: 99%

“…Proteomics is a valuable complement to genetic studies. Mass spectrometry (MS)-based proteomics profiling of patient-derived samples has been suggested as an effective approach for the discovery of biomarkers and detection of suitable therapeutic targets in many cancers [7][8][9][10].…”

mentioning

confidence: 99%

“…In a previous study [10], we identified YAP1 as a differentially expressed protein between pancreatic cancer and normal controls using MS-based proteomics profiling. In the present study, we investigate the prognostic utility and the biological significance of YAP1 in pancreatic cancer using large and clinically well-annotated cohorts, complemented by bioinformatics and in vitro experimental analyses.…”

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YAP1 is an independent prognostic marker in pancreatic cancer and associated with extracellular matrix remodeling

et al. 2020

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Background: Pancreatic cancer is a major cause of cancer-related mortality. The identification of effective biomarkers is essential in order to improve management of the disease. Yes-associated protein 1 (YAP1) is a downstream effector of the Hippo pathway, a signal transduction system implicated in tissue repair and regeneration, as well as tumorigenesis. Here we evaluate the biomarker potential of YAP1 in pancreatic cancer tissue. Methods: YAP1 was selected as a possible biomarker for pancreatic cancer from global protein sequencing of fresh frozen pancreatic cancer tissue samples and normal pancreas controls. The prognostic utility of YAP1 was evaluated using mRNA expression data from 176 pancreatic cancer patients in The Cancer Genome Atlas (TCGA), as well as protein expression data from immunohistochemistry analysis of a local tissue microarray (TMA) cohort comprising 140 pancreatic cancer patients. Ingenuity Pathway Analysis was applied to outline the interaction network for YAP1 in connection to the pancreatic tumor microenvironment. The expression of YAP1 target gene products was evaluated after treatment of the pancreatic cancer cell line Panc-1 with three substances interrupting YAP-TEAD interaction, including Super-TDU, Verteporfin and CA3. Results: Mass spectrometry based proteomics showed that YAP1 is the top upregulated protein in pancreatic cancer tissue when compared to normal controls (log2 fold change 6.4; p = 5E−06). Prognostic analysis of YAP1 demonstrated a significant correlation between mRNA expression level data and reduced overall survival (p = 0.001). In addition, TMA and immunohistochemistry analysis suggested that YAP1 protein expression is an independent predictor of poor overall survival [hazard ratio (HR) 1.870, 95% confidence interval (CI) 1.224-2.855, p = 0.004], as well as reduced disease-free survival (HR 1.950, 95% CI 1.299-2.927, p = 0.001). Bioinformatic analyses coupled with in vitro assays indicated that YAP1 is involved in the transcriptional control of target genes, associated with extracellular matrix remodeling, which could be modified by selected substances disrupting the YAP1-TEAD interaction. Conclusions: Our findings indicate that YAP1 is an important prognostic biomarker for pancreatic cancer and may play a regulatory role in the remodeling of the extracellular matrix.

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BASP1 expression is associated with poor prognosis and is correlated with immune infiltration in gastric cancer

et al. 2023

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BASP1 is a membrane‐bound protein that plays a promotional or inhibitory role in a variety of tumors; however, its role in gastric cancer (GC) and in the immune microenvironment has not been reported. The objectives of this study were to determine whether BASP1 is a valuable prognostic marker for GC and to explore its role in the immune microenvironment of GC. The expression level of BASP1 in GC was analyzed based on the TCGA dataset and further verified using GSE54129 and GSE161533 datasets, immunohistochemistry, and western blotting. The association between BASP1 and clinicopathological characteristics, as well as its predictive value, were examined using the STAD dataset. Cox regression analysis was performed to determine whether BASP1 can be used as an independent prognostic indicator for GC, and a nomogram was constructed to predict OS. The association between BASP1 and immune cell infiltration, immune checkpoints, and immune cell markers was confirmed by enrichment analysis, as well as analysis based on the TIMER and GEPIA databases. BASP1 was observed to be highly expressed in GC and was associated with a poor prognosis. The expression of BASP1 was positively correlated with the expression of immune checkpoints and immune cell markers, as well as immune cell infiltration. Thus, BASP1 may serve as a standalone prognostic indicator for GC. BASP1 is highly correlated with immune processes, and its expression is positively correlated with the degree of immune cell infiltration, immune checkpoints, and immune cell markers.

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Quantitative proteomics identifies brain acid soluble protein 1 (BASP1) as a prognostic biomarker candidate in pancreatic cancer tissue

Cited by 46 publications

References 56 publications

The brain acid‐soluble protein 1 (BASP1) interferes with the oncogenic capacity of MYC and its binding to calmodulin

The brain acid‐soluble protein 1 (BASP1) interferes with the oncogenic capacity of MYC and its binding to calmodulin

YAP1 is an independent prognostic marker in pancreatic cancer and associated with extracellular matrix remodeling

BASP1 expression is associated with poor prognosis and is correlated with immune infiltration in gastric cancer

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