Mass Spectrometric Comparison of HPV-Positive and HPV-Negative Oropharyngeal Cancer
Abstract
1. Introduction
2. Material and Methods
2.1. Patient Characteristics
2.2. Sample Preparation and Processing
2.2.1. Tissue Sectioning and Protein Extraction
2.2.2. Tryptic Digestion and Desalting
2.2.3. LC–MS/MS Analysis
2.3. Peptide Identification and Quantitative Proteomics
2.4. Random Forest Analysis
2.5. Analyses of Identified Proteins
2.6. Tissue Microarray (TMA) Analysis
2.7. Analysis of Patient Survival
3. Results
3.1. Pathways and Functions of Identified Proteins
3.1.1. DNA Replication Factors (MCM2/3/5/6/7, RBBP4)
3.1.2. Nuclear Architecture (Lamin B1, LAP2, NUP210, Numa1)
3.1.3. Regulators of the Cytoskeleton (APR3, CAPG, Gelsolin, Stathmin, Numa1, CCT8, RhoA/B/C)
3.2. Immunohistochemistry (IHC)
4. Discussion
4.1. Implications for Tumor Biology
4.2. Limitations of Our Study
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Cohort | p16-Positive | p16-Negative |
---|---|---|
Number of patients | 8 | 9 |
Age, median (range) (p = 0.6993) | 64.9 (59–76) | 66.8 (53–83) |
Sex (p = 1) | ||
Male | 6 | 7 |
Female | 2 | 2 |
pT classification (p = 0.8756) | ||
T1 | 4 | 6 |
T2 | 2 | 2 |
T3 | 1 | 1 |
T4 | 1 | 0 |
pN classification (p = 0.1316) | ||
N0 | 0 | 4 |
N1 | 3 | 1 |
N2 | 4 | 4 |
N3 | 1 | 0 |
TNM stage (7th ed.) (p = 0.2467) | ||
I | 0 | 2 |
II | 0 | 2 |
III | 3 | 1 |
IV | 5 | 4 |
ECS (p = 1) | ||
Pos | 3 | 3 |
Neg | 5 | 6 |
smoking (p = 0.2941) | ||
Yes | 5 | 8 |
No | 3 | 1 |
No | Gene (Protein) Names | Boruta Score | p-Value | Log2FC (HPV+/−) | p-Value (Sepiashvili et al.) [29] | Log2FC (HPV+/−) (Sepiashvili et al.) |
---|---|---|---|---|---|---|
1 | MCM2 | 200 | 0.000235 | 2.8231 | 0.000573 | 1.1887 |
2 | NUP210 | 200 | 0.000261 | 1.3284 | 0.000764 | 1.5418 |
3 | LMNB1 (Lamin B1) | 200 | 0.000651 | 0.8628 | 0.002252 | 0.5517 |
4 | TOP2B | 200 | 0.004052 | 1.3653 | 0.007912 | 0.6057 |
5 | CDKN2A (p16) | 200 | 0.004598 | 1.3982 | 0.000002 | 3.3464 |
6 | RHOA; RHOC; RHOB | 200 | 0.012392 | 0.8633 | 0.6526 (RHOA) | 0.0336 (RHOA) |
7 | STMN1; STMN2 (Stathmin; Stathmin-2) | 196 | 0.001886 | 1.0479 | 0.0544 (STMN1); 0.0050 (STMN2) | 0.3838 (STMN1) 1.1807 (STMN2) |
8 | ACTR3 (ARP3) | 196 | 0.005275 | 0.4038 | 0.042775 | 0.3757 |
9 | UBA52; RPS27A; UBB; UBC | 132 | 0.001915 | 0.4820 | 0.0601 (UBA52); 0.0765 (RPS27A) | 0.3174 (UBA52); 0.3108 (RPS27A) |
10 | SKP1 | 72 | 0.001183 | 2.0275 | 0.015037 | 2.1586 |
11 | HEBP2 | 46 | 0.056098 | 0.8142 | 0.186598 | 0.4573 |
12 | HLA-DRB1; HLA-DRB5 | 40 | 0.002618 | 2.6530 | 0.006311 | 0.8931 |
13 | CAPG | 34 | 0.002681 | 0.8428 | 0.000616 | 0.7927 |
14 | HIST1H4A | 34 | 0.011118 | 0.5163 | 0.076559 | 0.2950 |
15 | HIST2H2BE; HIST1H2BB; HIST1H2BO; HIST1H2BJ; HIST3H2BB (Histone H2B, multiple types) | 24 | 0.010950 | 0.7303 | 0.1806 (HIST1H2BB); 0.1988 (HIST1H2BJ); 0.1244 (HIST3H2BB) | 0.2649 (HIST1H2BB); 0.2754 (HIST1H2BJ); 0.3035 (HIST3H2BB) |
16 | INPP1 | 20 | 0.041938 | 1.2062 | n. d. | n. d. |
17 | MCM5 | 18 | 0.002374 | 1.5963 | 0.005306 | 1.3743 |
18 | LRPPRC | 18 | 0.085066 | −1.1076 | 0.060111 | −0.5621 |
19 | MCM6 | 16 | 0.007168 | 1.5859 | 0.000426 | 1.2566 |
20 | CCT8 | 14 | 0.022356 | 0.4512 | 0.463460 | 0.1661 |
21 | TMPO (LAP2) | 12 | 0.005542 | 1.0096 | 0.016226 | 1.0534 |
22 | RBBP4;RBBP7 | 10 | 0.003404 | 1.1455 | 0.0707 (RBBP4) 0.9507 (RBBP7) | −0.4031 (RBBP4) −0.0165 (RBBP7) |
23 | SLC3A2 | 10 | 0.006046 | −1.5631 | 0.317565 | −0.4671 |
24 | GSN (Gelsolin) | 10 | 0.027809 | 0.6165 | 0.029810 | 0.3432 |
25 | CTTN (Cortactin) | 1 | 0.015119 | −1.2674 | 0.000396 | −1.2752 |
26 | MCM3 | 0 | 0.014093 | 1.5990 | 0.000023 | 1.3652 |
27 | NUMA1 | 0 | 0.016250 | 1.5247 | 0.000340 | 1.1813 |
28 | MCM7 | 0 | 0.028008 | 1.2418 | 0.000820 | 1.0757 |
29 | AKR1B10 | 0 | 0.035758 | −2.6277 | 0.042775 | −1.0294 |
30 | ICAM1 | 0 | 0.037439 | 1.2982 | 0.000168 | 3.5303 |
31 | PTPRC | 0 | 0.042037 | 1.0681 | 0.012870 | 1.0362 |
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Wurlitzer, M.; Möckelmann, N.; Kriegs, M.; Vens, M.; Omidi, M.; Hoffer, K.; von Bargen, C.; Möller-Koop, C.; Witt, M.; Droste, C.; et al. Mass Spectrometric Comparison of HPV-Positive and HPV-Negative Oropharyngeal Cancer. Cancers 2020, 12, 1531. https://doi.org/10.3390/cancers12061531
Wurlitzer M, Möckelmann N, Kriegs M, Vens M, Omidi M, Hoffer K, von Bargen C, Möller-Koop C, Witt M, Droste C, et al. Mass Spectrometric Comparison of HPV-Positive and HPV-Negative Oropharyngeal Cancer. Cancers. 2020; 12(6):1531. https://doi.org/10.3390/cancers12061531
Chicago/Turabian StyleWurlitzer, Marcus, Nikolaus Möckelmann, Malte Kriegs, Maren Vens, Maryam Omidi, Konstantin Hoffer, Clara von Bargen, Christina Möller-Koop, Melanie Witt, Conrad Droste, and et al. 2020. "Mass Spectrometric Comparison of HPV-Positive and HPV-Negative Oropharyngeal Cancer" Cancers 12, no. 6: 1531. https://doi.org/10.3390/cancers12061531
APA StyleWurlitzer, M., Möckelmann, N., Kriegs, M., Vens, M., Omidi, M., Hoffer, K., von Bargen, C., Möller-Koop, C., Witt, M., Droste, C., Oetting, A., Petersen, H., Busch, C.-J., Münscher, A., Schlüter, H., Clauditz, T. S., & Rieckmann, T. (2020). Mass Spectrometric Comparison of HPV-Positive and HPV-Negative Oropharyngeal Cancer. Cancers, 12(6), 1531. https://doi.org/10.3390/cancers12061531