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Table 3 Classification to nearest shrunken centroids for identification of the most class-discriminating proteins

From: Proteomics-based insights into mitogen-activated protein kinase inhibitor resistance of cerebral melanoma metastases

Acc. Nr.

Protein name

Gene name

log2 fold change (t-test difference)

upregulated in poor responder

p value

t-test significant

Functional role

P21266

Glutathione S-transferase Mu 3

GSTM3

2.68

7.13E − 07

*

Uptake and detoxification of endogenous compounds and xenobiotics at the blood brain barrier [80]; many anticancer drugs are substrates for GST and, therefore, overexpression of GST is responsible for resistance to anti-cancer drugs in tumor cell lines [81]

P61962

DDB1- and CUL4-associated factor 7

DCAF7

2.06

1.11E − 07

*

Substrate receptor for a ubiquitin-protein ligase complex; involved in the pathway protein ubiquitination; involved in normal and disease skin development [82]; has been shown to function as a scaffold protein for protein complexes involved in kinase signalling [83]

P62937

Peptidyl-prolyl cis–trans isomerase A

PPIA

0.75

4.98E − 07

 

Upregulated in resistant human breast cancer cell line (vs. sensitive cell line) [84]; PPIases accelerate the folding of proteins; catalyzes the cis–trans isomerization of proline imidic peptide bonds in oligopeptides [85]

Q16864

V-type proton ATPase subunit F

ATP6V1F

3.12

5.47E − 07

*

V-ATPases are responsible for acidifying intracellular compartments [86]; an acidic environment leads to inactivation of T cells [56, 57]; supports the hypothesis that resistance is caused by the tumor inactivating immune cells

Q6FI81

Anamorsin

CIAPIN1

2.46

2.38E − 05

 

Anti-apoptotic effects in the cell; involved in negative control of cell death upon cytokine withdrawal [87]; may participate in breast cancer multi drug resistance (MDR) by regulating MDR1 and P53 expression, changing cell cycle and enhancing the anti-apoptotic capability of cells [88]

Q6UWP2

Dehydrogenase/reductase SDR family member 11

DHRS11

2.10

1.64E − 07

*

Involved in estrogen biosynthesis, which is part of steroid biosynthesis [89]; proposed role in sex hormone, neurosteroid, androgen, estrogen and bile acid metabolism; mRNA highly expressed in testis, small intestine, colon, kidney and cancer cell lines [90]

Q7Z7E8

Ubiquitin-conjugating enzyme E2 Q1

UBE2Q1

1.80

3.14E − 05

 

Catalyzes the covalent attachment of ubiquitin to other proteins [91]; may function as an oncogene that induces proliferation of cancer cells, and could be a novel diagnostic tool and a potential therapeutic target for colorectal cancer (CRC) [92]

Q8IVD9

NudC domain-containing protein 3

NUDCD3

2.42

2.78E − 05

 

Interacts selectively and non-covalently with an unfolded protein; functions to maintain the stability of dynein intermediate chain [93]; depletion of this gene product results in aggregation and degradation of dynein intermediate chain, mislocalization of the dynein complex from kinetochores, spindle microtubules, and spindle poles, and loss of gamma-tubulin from spindle poles [94]

Q8N4Q0

Prostaglandin reductase 3

ZADH2

2.48

2.44E − 06

*

Negatively modulates adipogenesis through regulation of PPARγ activity [95]; knockdown of prostaglandin reductase 1 (PTGR1) suppresses prostate cancer cell proliferation by inducing cell cycle arrest and apoptosis [96]

  1. The table shows UniProt accession number (Acc. Nr.), protein name, gene name, t-test difference between LFQ values of poor and good responding patients (fold change, logarithmic scale to the base of two) with corresponding p values and t-test significance (rows with a t-test result above s0 = 0.5 and FDR 0.01 are reported as significant)