bims-prodis 2018-04-29 papers

Issue of 2018–04–29
three papers selected by
Nancy Gough, Bioserendipity

J Proteome Res. 2018 Apr 22.

Proteomic Analysis of Cancer Associated Fibroblasts Reveal a Paracrine Role for MFAP5 in Human Oral Tongue Squamous Cell Carcinoma.

Simona Principe, Salvador Mejia-Guerrero, Vladimir Ignatchenko, Ankit Sinha, Alex Ignatchenko, Wei Shi, Keira Pereira, Susie Su, Shao Hui Huang, Brian O'Sullivan, Wei Xu, David Goldstein, Ilan Weinreb, Laurie Ailles, Fei-Fei Liu, Thomas Kislinger.

Bidirectional communication between cells and their microenvironment is crucial for both normal tissue homeostasis and tumor growth. During the development of oral tongue squamous cell carcinoma (OTSCC), cancer-associated fibroblasts (CAFs) create a supporting niche by maintaining a bidirectional crosstalk with cancer cells, mediated by classically secreted factors and various nanometer-sized vesicles, termed as extracellular vesicles (EVs). To better understand the role of CAFs within the tumor stroma and elucidate the mechanism by which secreted proteins contribute to OTSCC progression, we isolated and characterized patient-derived CAFs from resected tumors with matched adjacent tissue fibroblasts (AFs). Our strategy employed shotgun proteomics to comprehensively characterize the proteomes of these matched fibroblast populations. Our goals were to identify CAF secreted factors (EVs and soluble) that can functionally modulate OTSCC cells in vitro and to identify novel CAF-associated biomarkers. Comprehensive proteomic analysis identified 4,247 proteins, the most detailed description of a pro-tumorigenic stroma to date. We demonstrated functional effects of CAF secretomes (EVs and conditioned media) on OTSCC cell growth and migration. Comparative proteomics identified novel proteins associated with a CAF-like state. Specifically, MFAP5, a protein component of extracellular microfibrils, was enriched in CAF secretomes. Using in vitro assays, we demonstrated that MFAP5 activated OTSCC cell growth and migration via activation of MAPK and AKT pathways. Using a tissue microarray (TMA) of richly annotated primary human OTSCCs, we demonstrated an association of MFAP5 expression with patient survival. In summary, our proteomics data of patient derived stromal fibroblasts provide a useful resource for future mechanistic and biomarker studies.

DOI: https://doi.org/10.1021/acs.jproteome.7b00925

Clin Biochem. 2018 Apr 19. pii: S0009-9120(17)31281-X. [Epub ahead of print]

Serum retinol binding protein 4 and galectin-3 binding protein as novel markers for postmenopausal nonalcoholic fatty liver disease.

Hong Cai, Sha Lu, Yueming Chen, Sayantana Das Mbbs Mrcog, Zheng Niu, Guangchao Zhuo, Lei Lai, Zhifen Zhang.

OBJECTIVE: To investigate the differential protein expression before and after menopause in women with nonalcoholic fatty liver disease (NAFLD) and to explore novel markers for menopausal NAFLD.
METHODS: Eight serum samples collected from pre- or post-menopausal women with NAFLD were analysed by iTRAQ 2D-LC-MS/MS. Two protein candidates were selected and verified by enzyme-linked immunosorbent assay (ELISA) in serum samples collected from a one hundred and fifty-three female population subsequently, including 51 in post-menopausal status with NAFLD, 41 in pre-menopausal with NAFLD, 19 healthy individuals in post-menopausal status and 42 healthy pre-menopausal women.
RESULTS: A total of one hundred and sixty-seven proteins exhibiting significant changes were characterized, among which sixty-five were up-regulated and one hundred and two were down-regulated. Of those altered proteins, the expression of serum retinol binding protein 4 (RBP4) and galectin-3 binding protein (LGALS3BP) was obviously increased in the post-menopausal patient group compared to the other. ELISA validations for the two proteins were consistent with the proteomic profiling.
CONCLUSIONS: Serum RBP4 and LGAL3BP were up-regulated after menopause under NAFLD conditions, which suggested the two proteins may be potential markers as NAFLD in postmenopausal population.

Keywords: Galectin-3 binding protein; Menopause; Nonalcoholic fatty liver disease; Proteomics; Serum retinol binding protein 4

DOI: https://doi.org/10.1016/j.clinbiochem.2018.04.017

J Am Soc Hypertens. 2018 Mar 21. pii: S1933-1711(18)30075-5. [Epub ahead of print]

Epidemiologic observations guiding clinical application of a urinary peptidomic marker of diastolic left ventricular dysfunction.

Zhen-Yu Zhang, Esther Nkuipou-Kenfack, Wen-Yi Yang, Fang-Fei Wei, Nicholas Cauwenberghs, Lutgarde Thijs, Qi-Fang Huang, Ying-Mei Feng, Joost P Schanstra, Tatiana Kuznetsova, Jens-Uwe Voigt, Peter Verhamme, Harald Mischak, Jan A Staessen.

Hypertension, obesity, and old age are major risk factors for left ventricular (LV) diastolic dysfunction (LVDD), but easily applicable screening tools for people at risk are lacking. We investigated whether HF1, a urinary biomarker consisting of 85 peptides, can predict over a 5-year time span mildly impaired diastolic LV function as assessed by echocardiography. In 645 white Flemish (50.5% women; 50.9 years [mean]), we measured HF1 by capillary electrophoresis coupled with mass spectrometry in 2005-2010. We measured early (E) and late (A) peak velocities of the transmitral blood flow and early (e') and late (a') mitral annular peak velocities and their ratios in 2009-2013. In multivariable-adjusted analyses, per 1-standard deviation increment in HF1, e' was -0.193 cm/s lower (95% confidence interval: -0.352 to -0.033; P = .018) and E/e' 0.174 units higher (0.005-0.342; P = .043). Of 645 participants, 179 (27.8%) had LVDD at follow-up, based on impaired relaxation in 69 patients (38.5%) or an elevated filling pressure in the presence of a normal (74 [43.8%]) or low (36 [20.1%]) age-specific E/A ratio. For a 1-standard deviation increment in HF1, the adjusted odds ratio was 1.37 (confidence interval, 1.07-1.76; P = .013). The integrated discrimination (+1.14%) and net reclassification (+31.7%) improvement of the optimized HF1 threshold (-0.350) in discriminating normal from abnormal diastolic LV function at follow-up over and beyond other risk factors was significant (P ≤ .024). In conclusion, HF1 may allow screening for LVDD over a 5-year horizon in asymptomatic people.

Keywords: Diastolic left ventricular function; population science; screening; urinary proteomics

DOI: https://doi.org/10.1016/j.jash.2018.03.007