Multi-Omic Biomarkers as Potential Tools for the Characterisation of Pancreatic Cystic Lesions and Cancer: Innovative Patient Data Integration

Kane, Laura; Mellotte, Gregory S.; Conlon, Kevin C.; Ryan, Barbara; Maher, Stephen G.

doi:10.3390/cancers13040769

Cited by 14 publications

(14 citation statements)

References 125 publications

(222 reference statements)

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“…However, CA19-9 also gives false positive results in benign pancreaticobiliary diseases [ 14 , 15 ]. Several studies reported a number of non-invasive diagnostic and/or prognostic markers of pancreatic cancer that have been tested alone or in combination, such as: CA125, CEA, CEACAM1, MUC1, MIC1/GDF15, REG3A/PAP1, PKM2 and AXL, as well as auto-antibodies, fecal microbiome signatures and myeloid-derived suppressor cells [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ]. Yet, the clinical utility of these markers remains to be determined.…”

Section: Introductionmentioning

confidence: 99%

“…In search of original biomarkers for PDAC, we started from the consideration that cell transformation by the KRAS oncogene generates protein dysregulation in the affected cells. It is well established that proteins secreted by cancer cells display several differences compared to normal counterparts, and secreted proteins may contribute to cancer-associated features [ 22 , 24 , 26 , 30 ].…”

Section: Introductionmentioning

confidence: 99%

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Oncogenic KRAS-Induced Protein Signature in the Tumor Secretome Identifies Laminin-C2 and Pentraxin-3 as Useful Biomarkers for the Early Diagnosis of Pancreatic Cancer

Kamal

Siddiqui

Belgiovine

et al. 2022

Cancers

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KRAS mutations characterize pancreatic cell transformation from the earliest stages of carcinogenesis, and are present in >95% of pancreatic ductal adenocarcinoma (PDAC) cases. In search of novel biomarkers for the early diagnosis of PDAC, we identified the proteins secreted by the normal human pancreatic cell line (HPDE) recently transformed by inducing the overexpression of the KRASG12V oncogene. We report a proteomic signature of KRAS-induced secreted proteins, which was confirmed in surgical tumor samples from resected PDAC patients. The putative diagnostic performance of three candidates, Laminin-C2 (LAMC2), Tenascin-C (TNC) and Pentraxin-3 (PTX3), was investigated by ELISA quantification in two cohorts of PDAC patients (n = 200) eligible for surgery. Circulating levels of LAMC2, TNC and PTX3 were significantly higher in PDAC patients compared to the healthy individuals (p < 0.0001). The Receiver Operating Characteristics (ROC) curve showed good sensitivity (1) and specificity (0.63 and 0.85) for LAMC2 and PTX3, respectively, but not for TNC, and patients with high levels of LAMC2 had significantly shorter overall survival (p = 0.0007). High levels of LAMC2 and PTX3 were detected at early stages (I–IIB) and in CA19-9-low PDAC patients. In conclusion, pancreatic tumors release LAMC2 and PTX3, which can be quantified in the systemic circulation, and may be useful in selecting patients for further diagnostic imaging.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Oncogenic KRAS-Induced Protein Signature in the Tumor Secretome Identifies Laminin-C2 and Pentraxin-3 as Useful Biomarkers for the Early Diagnosis of Pancreatic Cancer

Kamal

Siddiqui

Belgiovine

et al. 2022

Cancers

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“…By comparison, colorectal cancer-related protein-coding genes have little overlap with known cancer genes, this is one of the advantages of proteomics over other omics ( 29 , 56 ). It is logical therefore to examine this extensive information in parallel with the aim of revealing those attributes that can be considered robust and sensitive enough to work as a biomarker of patient risk ( 57 ).…”

Section: Discussionmentioning

confidence: 99%

SAMHD1 as a prognostic and predictive biomarker in stage II colorectal cancer: A multicenter cohort study

You

Zhang²,

Yan³

et al. 2022

Front. Oncol.

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BackgroundThe identification of high-risk population patients is key to the personalized treatment options for the stage II colorectal cancers. The use of proteomics in the prognosis of patients with stage II colorectal cancer remains unclear.MethodsUsing quantitative proteomics, we analyzed proteins that are differentially expressed in the tumor and adjacent normal tissues of 11 paired colorectal cancer patients with and without recurrence selected by a nested case-control design. Of the 21 identified proteins, we selected one candidate protein. The association of the corresponding gene of the selected protein with overall survival (OS) and adjuvant chemotherapy was analyzed using two independent cohorts of patients with stages II colorectal cancer.ResultsSterile α motif and histidine-aspartate domain-containing protein 1 (SAMHD1) was selected as the candidate biomarker. A group of 124 patients (12.5%) were stratified into SAMHD1-high subgroup. The 5-year OS rate of SAMHD1-high patients was lower than that of SAMHD1-low patients with stage II colorectal cancer (discovery cohort: hazard ratio [HR] = 2.89, 95% confidence interval [CI], 1.17-7.18, P = 0.016; validation cohort: HR = 2.25, 95% CI, 1.17-4.34, P = 0.013). The Cox multivariate analysis yielded similar results. In a pooled database, the 5-year OS rate was significantly different between patients with and without adjuvant chemotherapy among stage II SAMHD1-low tumors than in patients with stage II SAMHD1-high tumors (88% vs. 77%, P = 0.032).ConclusionsSAMHD1-high expression could help in identifying patients with stage II colorectal cancer with poor prognosis and less benefit from adjuvant chemotherapy.

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“…In other instances, gene expression is controlled by metabolites [82][83][84][85][86][87]. Metabolites are active participants in enzymatic reactions [88][89][90][91][92][93] and they control protein and cellular functions [94][95][96][97][98] so they are essential in comprehensively characterizing disease pathogenesis [99][100][101][102][103][104]. This review article focuses on the metabolomic profile of prostate cancer (PCa) and the current state of metabolomics-diverse omics integration in PCa research.…”

Section: Integration Of Metabolomics To Other Omic Platformsmentioning

confidence: 99%

The Integration of Metabolomics with Other Omics: Insights into Understanding Prostate Cancer

Resurreccion

Fong

2022

Metabolites

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Our understanding of prostate cancer (PCa) has shifted from solely caused by a few genetic aberrations to a combination of complex biochemical dysregulations with the prostate metabolome at its core. The role of metabolomics in analyzing the pathophysiology of PCa is indispensable. However, to fully elucidate real-time complex dysregulation in prostate cells, an integrated approach based on metabolomics and other omics is warranted. Individually, genomics, transcriptomics, and proteomics are robust, but they are not enough to achieve a holistic view of PCa tumorigenesis. This review is the first of its kind to focus solely on the integration of metabolomics with multi-omic platforms in PCa research, including a detailed emphasis on the metabolomic profile of PCa. The authors intend to provide researchers in the field with a comprehensive knowledge base in PCa metabolomics and offer perspectives on overcoming limitations of the tool to guide future point-of-care applications.

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Multi-Omic Biomarkers as Potential Tools for the Characterisation of Pancreatic Cystic Lesions and Cancer: Innovative Patient Data Integration

Cited by 14 publications

References 125 publications

Oncogenic KRAS-Induced Protein Signature in the Tumor Secretome Identifies Laminin-C2 and Pentraxin-3 as Useful Biomarkers for the Early Diagnosis of Pancreatic Cancer

Oncogenic KRAS-Induced Protein Signature in the Tumor Secretome Identifies Laminin-C2 and Pentraxin-3 as Useful Biomarkers for the Early Diagnosis of Pancreatic Cancer

SAMHD1 as a prognostic and predictive biomarker in stage II colorectal cancer: A multicenter cohort study

The Integration of Metabolomics with Other Omics: Insights into Understanding Prostate Cancer

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