The absolute quantification of eight inter‐α‐trypsin inhibitor heavy chain 4 (ITIH<sub>4</sub>)‐derived peptides in serum from breast cancer patients

Broek, Irene van den; Sparidans, Rolf W.; Winden, Annemieke W J van; Gast, Marie-Christine W.; Dulken, Eric J van; Schellens, Jan H.M.; Beijnen, Jos H.

doi:10.1002/prca.201000035

Cited by 37 publications

(26 citation statements)

References 34 publications

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“…ITIH4, a protein secreted by the liver in times of trauma and involved in the acute-phase response, was shown to have a downward trend as the amount of n-3 fatty acids increased in the dietary groups. In serum from breast cancer patients it was shown that this protein as peptide fragments was upregulated in comparison to healthy controls (46,47). ITIH4 has also proposed to be cleaved by plasma kallikrein in cancers such as ovarian and breast (47,48) which could possibly explain the bands seen at 120 kDa (data not shown) and 100 kDa.…”

Section: Discussionmentioning

confidence: 92%

“…In serum from breast cancer patients it was shown that this protein as peptide fragments was upregulated in comparison to healthy controls (46,47). ITIH4 has also proposed to be cleaved by plasma kallikrein in cancers such as ovarian and breast (47,48) which could possibly explain the bands seen at 120 kDa (data not shown) and 100 kDa. Thus, the downward trend of the expression is consistent with chemoprevention.…”

Section: Discussionmentioning

confidence: 92%

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Proteomic Changes Induced by Effective Chemopreventive Ratios of n-3:n-6 Fatty Acids and Tamoxifen against MNU-Induced Mammary Cancer in the Rat

Skibinski

Thompson

Das

et al. 2013

Cancer Prevention Research

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We used a proteomic approach to gain insights into the mechanisms of protection at the protein level by a high n-3:n-6 ratio in the absence and presence of Tamoxifen. Four groups were treated with 1-methyl-1-nitrosourea (MNU) and fed the following diets with varied n-3:n-6 ratios; group 1 ¼ 1:1; groups 2 and 3 ¼ 10:1 and 25:1, respectively; group 4: (25:1) plus Tamoxifen (1 mg/kg diet). The plasma from six rats/group was pooled and analyzed with the isobaric tags for relative and absolute quantitation method; 148 proteins were identified with 95% confidence by ProteinPilot 4.0. In plasma of rats fed 10:1, 25:1 n-3:n-6, and 25:1 plus Tamoxifen, the number of proteins that met our criteria (P 0.05, error factor 2) were 10, 14, and 19 proteins, respectively. Selected proteins were further validated by Western blotting. Compared to 1:1, both 10:1 and 25:1 diets upregulated vitamin D binding protein, gelsolin, and 14-3-3 sigma, reported to have tumor suppressive effects, whereas alpha-1B-glycoprotein, which has been reported to be elevated in the serum of breast cancer patients was decreased. Compared to 25:1, the 25:1 plus Tamoxifen diet downregulated apolipoprotein E, haptoglobin, and inter-a-inhibitor H4 heavy chain. Ingenuity pathway analysis determined that the trends of specific proteins were related to lipid metabolism in the 25:1 n-3:n-6 group, whereas the 25:1 n-3:n-6 plus Tamoxifen group included proteins involved in cancer and inflammation. Our results show that several proteins were altered in a manner consistent with chemoprevention. Such proteins may serve as biomarkers to monitor efficacy of n-3 and Tamoxifen in future clinical chemoprevention trials. Cancer Prev Res; 6(9); 979-88. Ó2013 AACR.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 92%

Proteomic Changes Induced by Effective Chemopreventive Ratios of n-3:n-6 Fatty Acids and Tamoxifen against MNU-Induced Mammary Cancer in the Rat

Skibinski

Thompson

Das

et al. 2013

Cancer Prevention Research

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“…There are a few reports that proposed this protein as an OC marker [37, 42]. Changes in the levels of ITIH4-derived peptides were also observed in urine of early prostate cancer patients [43] and in the serum of breast cancer patients [44] and gastric adenocarcinoma patients [41]. A correlation was also suggested between different fragmentation of ITIH4 and disease conditions [45].…”

Section: Discussionmentioning

confidence: 99%

MALDI-TOF-MS analysis in discovery and identification of serum proteomic patterns of ovarian cancer

et al. 2017

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BackgroundDue to high mortality and lack of efficient screening, new tools for ovarian cancer (OC) diagnosis are urgently needed. To broaden the knowledge on the pathological processes that occur during ovarian cancer tumorigenesis, protein-peptide profiling was proposed.MethodsSerum proteomic patterns in samples from OC patients were obtained using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF). Eighty nine serum samples (44 ovarian cancer and 45 healthy controls) were pretreated using solid-phase extraction method. Next, a classification model with the most discriminative factors was identified using chemometric algorithms. Finally, the results were verified by external validation on an independent test set of samples.ResultsMain outcome of this study was an identification of potential OC biomarkers by applying liquid chromatography coupled with tandem mass spectrometry. Application of this novel strategy enabled the identification of four potential OC serum biomarkers (complement C3, kininogen-1, inter-alpha-trypsin inhibitor heavy chain H4, and transthyretin). The role of these proteins was discussed in relation to OC pathomechanism.ConclusionsThe study results may contribute to the development of clinically useful multi-component diagnostic tools in OC. In addition, identifying a novel panel of discriminative proteins could provide a new insight into complex signaling and functional networks associated with this multifactorial disease.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-017-3467-2) contains supplementary material, which is available to authorized users.

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“…18,19 Serum ITIH4 proteolytic fragments resulting from proteolytic processing of the PRR are also of interest due to their cancer biomarker potential. 20−22 …”

Section: Introductionmentioning

confidence: 99%

Site-Specific Glycan Microheterogeneity of Inter-Alpha-Trypsin Inhibitor Heavy Chain H4

et al. 2014

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Inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) is a 120 kDa acute-phase glycoprotein produced primarily in the liver, secreted into the blood, and identified in serum. ITIH4 is involved in liver development and stabilization of the extracellular matrix (ECM), and its expression is altered in liver disease. In this study, we aimed to characterize glycosylation of recombinant and serum-derived ITIH4 using analytical mass spectrometry. Recombinant ITIH4 was analyzed to optimize glycopeptide analyses, followed by serum-derived ITIH4. First, we confirmed that the four ITIH4 N-X-S/T sequons (N81, N207, N517, and N577) were glycosylated by treating ITIH4 tryptic/GluC glycopeptides with PNGaseF in the presence of 18O water. Next, we performed glycosidase-assisted LC–MS/MS analysis of ITIH4 trypsin-GluC glycopeptides enriched via hydrophilic interaction liquid chromatography to characterize ITIH4 N-glycoforms. While microheterogeneity of N-glycoforms differed between ITIH4 protein expressed in HEK293 cells and protein isolated from serum, occupancy of N-glycosylation sites did not differ. A fifth N-glycosylation site was discovered at N274 with the rare nonconsensus NVV motif. Site N274 contained high-mannose N-linked glycans in both serum and recombinant ITIH4. We also identified isoform-specific ITIH4 O-glycoforms and documented that utilization of O-glycosylation sites on ITIH4 differed between the cell line and serum.

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The absolute quantification of eight inter‐α‐trypsin inhibitor heavy chain 4 (ITIH₄)‐derived peptides in serum from breast cancer patients

Abstract: The obtained results particularly suggest potential for these ITIH(4)-derived peptides in the follow-up of breast cancer after surgery.

Cited by 37 publications

References 34 publications

Proteomic Changes Induced by Effective Chemopreventive Ratios of n-3:n-6 Fatty Acids and Tamoxifen against MNU-Induced Mammary Cancer in the Rat

Proteomic Changes Induced by Effective Chemopreventive Ratios of n-3:n-6 Fatty Acids and Tamoxifen against MNU-Induced Mammary Cancer in the Rat

MALDI-TOF-MS analysis in discovery and identification of serum proteomic patterns of ovarian cancer

Site-Specific Glycan Microheterogeneity of Inter-Alpha-Trypsin Inhibitor Heavy Chain H4

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The absolute quantification of eight inter‐α‐trypsin inhibitor heavy chain 4 (ITIH4)‐derived peptides in serum from breast cancer patients

Abstract: The obtained results particularly suggest potential for these ITIH(4)-derived peptides in the follow-up of breast cancer after surgery.

Cited by 37 publications

References 34 publications

Proteomic Changes Induced by Effective Chemopreventive Ratios of n-3:n-6 Fatty Acids and Tamoxifen against MNU-Induced Mammary Cancer in the Rat

Proteomic Changes Induced by Effective Chemopreventive Ratios of n-3:n-6 Fatty Acids and Tamoxifen against MNU-Induced Mammary Cancer in the Rat

MALDI-TOF-MS analysis in discovery and identification of serum proteomic patterns of ovarian cancer

Site-Specific Glycan Microheterogeneity of Inter-Alpha-Trypsin Inhibitor Heavy Chain H4

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The absolute quantification of eight inter‐α‐trypsin inhibitor heavy chain 4 (ITIH₄)‐derived peptides in serum from breast cancer patients