Quantitative mass spectrometry analysis reveals a panel of nine proteins as diagnostic markers for colon adenocarcinomas

Atak, Apurva; Khurana, S. K.; Gollapalli, Kishore; Reddy, Panga Jaipal; Levy, Roei; Ben-Salmon, Stav; Hollander, Dror; Donyo, Maya; Heit, Anke; Hotz‐Wagenblatt, Agnes; Biran, Hadas; Sharan, Roded; Rane, Shailendra; Shelar, Ashutosh; Ast, Gil; Srivastava, Sanjeeva

doi:10.18632/oncotarget.24418

Cited by 18 publications

(18 citation statements)

References 94 publications

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“…Our results confirm and extend previous reports indicating that serum peptide signatures could be used for the identification of CRC [ [34] , [35] , [36] , [37] , [38] ]. We propose SETD7 as a potential serum biomarker for CRC.…”

Section: Discussionsupporting

confidence: 92%

Histone-lysine N-methyltransferase SETD7 is a potential serum biomarker for colorectal cancer patients

et al. 2018

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BackgroundThere is an urgent need for the identification of new, clinically useful biomarkers of CRC to enhance diagnostic and prognostic capabilities.MethodsWe performed proteomic profiling on serum samples from paired pre- and post-operative CRC patients, colorectal polyps patients and healthy controls using an approach combining magnetic bead-based weak cation exchange and matrix-assisted laser desorption ionization-time of flight mass spectrometry. We next performed liquid chromatography-electrospray ionization-tandem mass spectrometry to identify the proteins and selected potential biomarker based on bioinformatics analysis of the TCGA and GEO dataset. We examined SETD7 expression in serum and tissue samples by ELISA and immunohistochemistry respectively and explored the biological function of SETD7 in vitro.Findings85 differentially expressed peptides were identified. Five peptides showing the most significant changes in abundance across paired pre- and post-operation CRC patients, colorectal polyps patients and healthy controls were identified as peptide regions of FGA, MUC5AC and SETD7. Bioinformatics analysis suggested that the up-regulation of SETD7 in CRC is relatively specific. Validation studies showed that SETD7 expression increased from healthy controls to those with colorectal polyps and finally CRC patients, and decreased after surgery. The sensitivity and specificity of SETD7 were 92.17% and 81.08%, with a high diagnostic value (AUC = 0.9477). In addition, SETD7 expression was significantly correlated with tumor stage and microsatellite instability. Knockdown of SETD7 inhibited cancer cell proliferation, induced G1/S cell cycle arrest and increased apoptosis.InterpretationOur data indicate that SETD7 could serve as a potential diagnostic and prognostic biomarker for CRC.

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Section: Discussionsupporting

confidence: 92%

Histone-lysine N-methyltransferase SETD7 is a potential serum biomarker for colorectal cancer patients

et al. 2018

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“…The current diagnosis strategies for COAD are time consuming, which include biopsy, laboratory tests, and colonoscopy. 3 Although enormous advances have been made for the diagnosis and treatment of COAD, approximately half of the patients have a recurrence or die within just 5 years. Due to the incapacity to detect COAD at an early stage, the diagnosis and prognosis of COAD are unsatisfactory.…”

Section: Introductionmentioning

confidence: 99%

Identification of long noncoding RNAs biomarkers for diagnosis and prognosis in patients with colon adenocarcinoma

Huang

Liu

et al. 2018

J of Cellular Biochemistry

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Background: In the study, we aimed to find key long noncoding RNAs (lncRNAs) significantly associated with the diagnosis of colon adenocarcinoma (COAD) and lncRNA signatures to provide survival risk prognosis for patients with COAD. Methods: The lncRNA and messenger RNA (mRNA) expression profiles and clinical information of patients with COAD were obtained from the Cancer Genome Atlas database. The differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) between COAD and normal tissues were identified. The optimal diagnostic and prognostic lncRNA biomarkers for COAD were identified by using feature selection procedure and classification model. Functional enrichment analysis revealed the possible roles of mRNAs coexpressed with lncRNAs in some cancerrelated biological processes and pathways. Receiver operating characteristic curve of these lncRNA biomarkers were obtained by using 10-fold cross-validation. Univariate and multivariate Cox regression analysis for these DElncRNAs were performed to obtain the lncRNAs related to overall survival time. The expression levels of selected DElncRNAs were validated by quantitative real time polymerase chain reaction (qRT-PCR).Results: A total of 169 DElncRNAs (60 downregulated and 109 upregulated) and 1236 DEmRNAs (708 downregulated and 528 upregulated) between COAD and normal tissues were identified. Eight lncRNAs of XXbac-B476C20.9, PP7080, CDKN2B-AS1, LINC00092, CA3-AS1, HAND2-AS1, CTD-2269F5.1, and LINC01082 were selected as optimal diagnostic lncRNA biomarkers for COAD. The expression of eight optimal diagnostic lncRNA biomarkers in qRT-PCR validation was consistent with our integrated analysis. Among them, XXbac-B476C20.9 was not only one of the eight optimal diagnostic lncRNA biomarkers, but also related to the prognosis of COAD. Conclusion: Our study demonstrated the promising potential of XXbac-B476C20.9as an independent biomarker for diagnosis and prognosis of patients with COAD. K E Y W O R D S biomarker, colon adenocarcinoma (COAD), long noncoding RNAs (lncRNAs), messenger RNA (mRNA) J Cell Biochem. 2019;120:4121-4131.wileyonlinelibrary.com/journal/jcb

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“…To find differentially expressed proteins in CRC vs. benign colonic mucosa, t-tests with 1% false discovery rate were performed, resulting in 197 up-regulated and 533 down-regulated proteins in tumor tissues, respectively ( Figure 1A). Reassuringly, several known CRC biomarkers, such as S100A9 and Tenascin-C, were found to be overexpressed in the tumor tissues by our mass spectrometric approach [12][13][14].…”

Section: Differential Protein Expression Analysis Of Colorectal Cancementioning

confidence: 81%

Prolyl 4-hydroxylase alpha 1 protein expression risk-stratifies early stage colorectal cancer

et al. 2020

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Colorectal cancer (CRC) is one of the most prevalent and lethal malignancies. Especially for early stage CRC, prognostic molecular markers are needed to guide therapy. In this study, we first extracted total proteomes from matched pairs of fresh cancer and benign mucosal tissues from 22 CRC patients. Global proteomic profiling with Fourier transform liquid chromatography-mass spectrometry sequencing and label free quantitation uncovered that P4HA1 (prolyl 4-hydroxylase alpha 1) was overexpressed in CRC relative to benign colonic mucosa. We then investigated expression by immunohistochemical staining with P4HA1-specific antibodies using CRC tissue microarrays. Independent validation cohorts of 599 cases of early stage CRC and 91 cases of late stage CRC were examined. Multivariate and univariate survival analyses revealed that high expression of P4HA1 protein was an independent poor prognostic marker for patients with early stage CRC, especially of the microsatellite stable subtype. Our study provides strong support for P4HA1 as a predictive protein marker for precision diagnostics, therapeutic decision-making, and drug development for early stage colorectal cancer and demonstrates the utility of proteomic profiling to identify novel protein biomarkers.

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Quantitative mass spectrometry analysis reveals a panel of nine proteins as diagnostic markers for colon adenocarcinomas

Cited by 18 publications

References 94 publications

Histone-lysine N-methyltransferase SETD7 is a potential serum biomarker for colorectal cancer patients

Histone-lysine N-methyltransferase SETD7 is a potential serum biomarker for colorectal cancer patients

Identification of long noncoding RNAs biomarkers for diagnosis and prognosis in patients with colon adenocarcinoma

Prolyl 4-hydroxylase alpha 1 protein expression risk-stratifies early stage colorectal cancer

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