Identification of potential breast cancer markers in nipple discharge by protein profile analysis using two-dimensional nano-liquid chromatography/nanoelectrospray ionization-mass spectrometry

Kurono, Sadamu; Kaneko, Yuka; Matsuura, Nariaki; Oishi, Haruki; Noguchi, Shinzaburo; Kim, Seung Jin; Tamaki, Yasuhiro; Aikawa, Tomonao; Kotsuma, Yoshikazu; Inaji, Hideo; Matsuura, Shuji

doi:10.1002/prca.201500016

Cited by 17 publications

(12 citation statements)

References 25 publications

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“…have found that CA2 and CA12 have prognostic power in colorectal carcinomas35; and Kurono et al . have reported that CA2 expression in breast cancer is significantly higher than normal tissues36. It is known that solid tumors are featured by the tumor microenvironment, with aberrant activation of numerous immune cells28.…”

Section: Discussionmentioning

confidence: 99%

SWATH-based proteomics identified carbonic anhydrase 2 as a potential diagnosis biomarker for nasopharyngeal carcinoma

Luo

Mok

Lin

et al. 2017

Sci Rep

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Nasopharyngeal carcinoma (NPC) is a serious threat to public health, and the biomarker discovery is of urgent needs. The data-independent mode (DIA) based sequential window acquisition of all theoretical fragment-ion spectra (SWATH) mass spectrometry (MS) has been proved to be precise in protein quantitation and efficient for cancer biomarker researches. In this study, we performed the first SWATH-MS analysis comparing the NPC and normal tissues. Spike-in stable isotope labeling by amino acids in cell culture (super-SILAC) MS was used as a shotgun reference. We identified and quantified 1414 proteins across all SWATH-MS analyses. We found that SWATH-MS had a unique feature to preferentially detect proteins with smaller molecular weights than either super-SILAC MS or human proteome background. With SWATH-MS, 29 significant differentially express proteins (DEPs) were identified. Among them, carbonic anhydrase 2 (CA2) was selected for further validation per novelty, MS quality and other supporting rationale. With the tissue microarray analysis, we found that CA2 had an AUC of 0.94 in differentiating NPC from normal tissue samples. In conclusion, SWATH-MS has unique features in proteome analysis, and it leads to the identification of CA2 as a potentially new diagnostic biomarker for NPC.

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Section: Discussionmentioning

confidence: 99%

SWATH-based proteomics identified carbonic anhydrase 2 as a potential diagnosis biomarker for nasopharyngeal carcinoma

Luo

Mok

Lin

et al. 2017

Sci Rep

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“…A number of strategies to determine the NAF proteome coverage have been undertaken many of which have been summarized by Pavlou et al, as part of a comparison with their own dataset of 854 proteins [20]. More recently, similar studies by Brunoro et al [21] and Kurono et al [22] identified 557 and 372 proteins, respectively. Mostly these studies have focused on optimizing protein and peptide separation using single breast samples from each patient.…”

Section: Clinical Relevancementioning

confidence: 99%

“…21 and Kurono et al. 22 identified 557 and 372 proteins, respectively. Mostly these studies have focused on optimizing protein and peptide separation using single breast samples from each patient.…”

Section: Introductionmentioning

confidence: 99%

Nipple aspirate fluid—A liquid biopsy for diagnosing breast health

Shaheed

Tait

Kyriacou

et al. 2017

Proteomics Clinical Apps

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PurposeNipple secretions are protein‐rich and a potential source of breast cancer biomarkers for breast cancer screening. Previous studies of specific proteins have shown limited correlation with clinicopathological features. Our aim, in this pilot study, was to investigate the intra‐ and interpatient protein composition of nipple secretions and the implications for their use as liquid biopsies.Experimental designMatched pairs of nipple discharge/nipple aspirate fluid (NAF, n = 15) were characterized for physicochemical properties and SDS‐PAGE. Four pairs were selected for semiquantitative proteomic profiling and trypsin‐digested peptides analyzed using 2D‐LC Orbitrap Fusion MS. The resulting data were subject to bioinformatics analysis and statistical evaluation for functional significance.ResultsA total of 1990 unique proteins were identified many of which are established cancer‐associated markers. Matched pairs shared the greatest similarity (average Pearson correlation coefficient of 0.94), but significant variations between individuals were observed.Conclusions and clinical relevanceThis was the most complete proteomic study of nipple discharge/nipple aspirate fluid to date providing a valuable source for biomarker discovery. The high level of milk proteins in healthy volunteer samples compared to the cancer patients was associated with galactorrhoea. Using matched pairs increased confidence in patient‐specific protein levels but changes relating to cancer stage require investigation of a larger cohort.

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“…Antibody columns may be used to deplete high-abundance plasma proteins from urine samples to allow for the detection of lower abundance proteins (8)(9)(10)(11)(12)(13)(14). Two-dimensional liquid chromatography (2D-LC) separation decreases sample complexity by using two columns prior to tandem mass spectrometry (MS/MS) and exhibits increased power in detecting low-abundance proteins (15,16). A method that combines antibody depletion with 2D-LC-MS/MS may facilitate the identification of biomarkers (17), although such a method has not previously been used to analyze nephrotic syndrome urine samples.…”

Section: Introductionmentioning

confidence: 99%

Proteomic profile-based screening of potential protein biomarkers in the urine of patients with nephrotic syndrome

Wang

Cai

Wang

et al. 2017

Molecular Medicine Reports

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Nephrotic syndrome is not a single disease; rather, it is a term for numerous diseases and pathological types. Renal biopsy is of use in determining the diagnosis and prognosis, and for guiding treatment; however, the use of this intervention is limited due to its invasive nature. Abnormal kidney‑derived proteins in the urine of patients provide useful information regarding numerous pathological processes that occur in the kidneys, and may be considered a potential non‑invasive biomarker for kidney disease. Proteomic analysis exhibits the advantage of being high‑throughput and has previously been used to identify biomarkers of disease. The present study aimed to identify abnormal kidney‑derived proteins in the urine of patients with nephrotic syndrome using a novel proteomic strategy. Urine samples from 5 patients with nephrotic syndrome were subjected to acetone precipitation and albumin/immunoglobulin G depletion prior to analysis by two‑dimensional liquid chromatography tandem mass spectrometry. The resulting data were compared to a publicly available proteomic database of normal human plasma/urine and normal human kidney in PeptideAtlas, and of normal human kidney in the Human Protein Atlas. Candidate biomarkers were validated using ELISA analysis in 60 patients with nephrotic syndrome: 30 with focal segmental glomerulosclerosis (FSGS) and 30 with minimal change disease (MCD), as well as in 30 healthy controls. The initial screening identified 809 proteins in the urine of patients with nephrotic syndrome. A total of 13/809 proteins were additionally present in the kidney proteome of PeptideAtlas and the Human Protein Atlas, although not in normal human urine and normal human plasma according to PeptideAtlas; these were referred to as 'kidney‑derived disease‑associated proteins'. One of the kidney‑derived disease‑associated proteins, ubiquitin‑60S ribosomal protein L40 (UBA52) was observed to be increased in the urine of patients compared with normal controls [Creatinine, 637 ng/mg (216‑1,851) vs. 1.89 ng/mg (1.37‑3.33), P<0.001; and 18.58 ng/mg (11.11‑46.25) vs. 1.89 ng/mg (1.37‑3.33), P<0.001)], and the urinary UBA52 levels were significantly increased in patients with FSGS compared with in patients with MCD (P<0.001). In conclusion, the present study identified potential novel urinary protein biomarkers for nephrotic syndrome, in addition to an extensive urinary proteomic profile of patients with nephrotic syndrome.

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Identification of potential breast cancer markers in nipple discharge by protein profile analysis using two-dimensional nano-liquid chromatography/nanoelectrospray ionization-mass spectrometry

Abstract: These tendencies in protein expression and markers provide new ways to identify breast cancer patients. Therefore, RP/RP 2D LC/MS/MS analyses of ND and the above three markers are supported as a new breast cancer diagnostic technique.

Cited by 17 publications

References 25 publications

SWATH-based proteomics identified carbonic anhydrase 2 as a potential diagnosis biomarker for nasopharyngeal carcinoma

SWATH-based proteomics identified carbonic anhydrase 2 as a potential diagnosis biomarker for nasopharyngeal carcinoma

Nipple aspirate fluid—A liquid biopsy for diagnosing breast health

Proteomic profile-based screening of potential protein biomarkers in the urine of patients with nephrotic syndrome

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