Glycoprotein screening in colorectal cancer based on differentially expressed Tn antigen

Wei, Haixia; Cheng, Zhiyong; Ouyang, Chunhui; Hu, Yawen; Chen, Shuijiao; Wang, Chunlian; Lu, Fanggen; Zhang, Jie; Wang, Yongjun; Liu, Xiaowei

doi:10.3892/or.2016.4937

Cited by 14 publications

(9 citation statements)

References 51 publications

(54 reference statements)

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“…The heterogeneity of glycosylation sites or changes in glycan structures in body fluids were shown to be correlated with the development and progression of certain cancer states [ 17 , 18 ]. Further, alteration of glycoprotein levels was reported in CRC [ 19 ], breast cancer [ 20 ], and prostate cancer [ 21 ]. Therefore, glycoproteins can be considered an ideal source for the early detection of cancers [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Clinical Assay for the Early Detection of Colorectal Cancer Using Mass Spectrometric Wheat Germ Agglutinin Multiple Reaction Monitoring

Tsai

et al. 2021

Cancers

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Colorectal cancer (CRC) is currently the third leading cause of cancer-related mortality in the world. U.S. Food and Drug Administration-approved circulating tumor markers, including carcinoembryonic antigen, carbohydrate antigen (CA) 19-9 and CA125 were used as prognostic biomarkers of CRC that attributed to low sensitivity in diagnosis of CRC. Therefore, our purpose is to develop a novel strategy for novel clinical biomarkers for early CRC diagnosis. We used mass spectrometry (MS) methods such as nanoLC-MS/MS, targeted LC-MS/MS, and stable isotope-labeled multiple reaction monitoring (MRM) MS coupled to test machine learning algorithms and logistic regression to analyze plasma samples from patients with early-stage CRC, late-stage CRC, and healthy controls (HCs). On the basis of our methods, 356 peptides were identified, 6 differential expressed peptides were verified, and finally three peptides corresponding wheat germ agglutinin (WGA)-captured proteins were semi-quantitated in 286 plasma samples (80 HCs and 206 CRCs). The novel peptide biomarkers combination of PF454–62, ITIH4429–438, and APOE198–207 achieved sensitivity 84.5%, specificity 97.5% and an AUC of 0.96 in CRC diagnosis. In conclusion, our study demonstrated that WGA-captured plasma PF454–62, ITIH4429–438, and APOE198–207 levels in combination may serve as highly effective early diagnostic biomarkers for patients with CRC.

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Section: Introductionmentioning

confidence: 99%

Clinical Assay for the Early Detection of Colorectal Cancer Using Mass Spectrometric Wheat Germ Agglutinin Multiple Reaction Monitoring

Tsai

et al. 2021

Cancers

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“…It has been reported that Tn antigen is detected in almost 90% of human colon cancer whereas it is rarely detected in normal tissue . Tn antigen expression is correlated with tumour invasion and poor prognosis in CRC patients, and it is proposed as a potential target for immunotherapy . Nevertheless, it remains elusive whether Tn antigen may play a causative role in colorectal cancer development and metastasis.…”

Section: Introductionmentioning

confidence: 99%

Tn antigen promotes human colorectal cancer metastasis via H‐Ras mediated epithelial‐mesenchymal transition activation

Liu

Dong

et al. 2019

J Cellular Molecular Medi

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Tn antigen is a truncated O‐glycan, frequently detected in colorectal cancer ( CRC ), but its precise role in CRC metastasis is not well addressed. Here we investigated the effects of Core 1 β3Gal‐T specific molecular chaperone (Cosmc) deletion‐mediated Tn antigen exposure on CRC metastasis and its underlying mechanism. We first used CRISPR /Cas9 technology to knockout Cosmc, which is required for normal O‐glycosylation, and thereby obtained Tn‐positive CRC cells. We then investigated the biological consequences of Tn antigen expression in CRC . The results showed that Tn‐positive cells exhibited an enhanced metastatic capability both in vitro and in vivo. A further analysis indicated that Tn antigen expression induced typical activation of epithelial‐mesenchymal transition ( EMT ). Mechanistically, we found that H‐Ras, which is known to drive EMT , was markedly up‐regulated in Tn‐positive cells, whereas knockdown of H‐Ras suppressed Tn antigen induced activation of EMT . Furthermore, we confirmed that LS 174T cells (Tn‐positive) transfected with wild‐type Cosmc, thus expressing no Tn antigen, had down‐regulation of H‐Ras expression and subsequent inhibition of EMT process. In addition, analysis of 438 samples in TCGA cohort demonstrated that Cosmc expression was reversely correlated with H‐Ras, underscoring the significance of Tn antigen‐H‐Ras signalling in CRC patients. These data demonstrated that Cosmc deletion‐mediated Tn antigen exposure promotes CRC metastasis, which is possibly mediated by H‐Ras‐induced EMT activation.

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“…Interestingly, tomoelastography was sensitive to lymphvascular invasion which was not detectable by CVF. This disparity in sensitivity of stiffness and CVF might be due to 1) the contribution of other ECM components than collagen such as fibronectin, proteoglycans, or glycosaminoglycans to tumor stiffness (47,48), or 2), in vivo factors such as blood perfusion and vascular resistance (49) to which tomoelastography is sensitive (17). Tumor angiogenesis and the migration status of neoplastic cells into the vasculature or the lymphatic system probably better reflects lymphvascular invasion than the amount of collagen in the ECM.…”

Section: Discussionmentioning

confidence: 99%

Rectal Tumor Stiffness Quantified by In Vivo Tomoelastography and Collagen Content Estimated by Histopathology Predict Tumor Aggressiveness

Guo

Pei

et al. 2021

Front. Oncol.

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PurposeTo investigate the significance of collagen in predicting the aggressiveness of rectal tumors in patients, examined in vivo based on tomoelastography quantified stiffness and ex vivo by histologically measured collagen volume fraction (CVF).Experimental Design170 patients with suspected rectal cancer were prospectively enrolled and underwent preoperative magnetic resonance imaging (MRI) and rectal tomoelastography, a technique based on multifrequency magnetic resonance elastography. Histopathologic analysis identified eighty patients with rectal cancer who were divided into subgroups by tumor-node (TN) stage, prognostic stage, and risk level. Rectal tumor stiffness was correlated with histopathologic CVF. Area-under-the-curve (AUC) and contingency analysis were used to evaluate the performance of rectal stiffness in distinguishing tumor stages which was compared to standard clinical MRIResultsIn vivo tomoelastography revealed that rectal tumor stiffened significantly with increased TN stage (p<0.05). Tumors with poorly differentiated status, perineural and lymphovascular invasion also displayed higher stiffness than well-to-moderately differentiated, noninvasive tumors (all p<0.05). Similar to in vivo stiffness, CVF indicated an abnormally high collagen content in tumors with perineural invasion and poor differentiation status. CVF was also positively correlated with stiffness (p<0.05). Most importantly, both stiffness (AUROC: 0.82) and CVF (AUROC: 0.89) demonstrated very good diagnostic accuracy in detecting rectal tumors that have high risk for progressing to an aggressive state with poorer prognosis.ConclusionIn human rectal carcinomas, overexpression of collagen is correlated with increased tissue stiffness and high risk for tumor advancing more aggressively. In vivo tomoelastography quantifies rectal tumor stiffness which improves the diagnostic performance of standard MRI in the assessment of lymph nodes metastasis. Therefore, in vivo stiffness mapping by tomoelastography can predict rectal tumor aggressiveness and add diagnostic value to MRI.

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Glycoprotein screening in colorectal cancer based on differentially expressed Tn antigen

Cited by 14 publications

References 51 publications

Clinical Assay for the Early Detection of Colorectal Cancer Using Mass Spectrometric Wheat Germ Agglutinin Multiple Reaction Monitoring

Clinical Assay for the Early Detection of Colorectal Cancer Using Mass Spectrometric Wheat Germ Agglutinin Multiple Reaction Monitoring

Tn antigen promotes human colorectal cancer metastasis via H‐Ras mediated epithelial‐mesenchymal transition activation

Rectal Tumor Stiffness Quantified by In Vivo Tomoelastography and Collagen Content Estimated by Histopathology Predict Tumor Aggressiveness

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