Identification of Potential Serum Protein Biomarkers and Pathways for Pancreatic Cancer Cachexia Using an Aptamer-Based Discovery Platform
Abstract
:Simple Summary
Abstract
1. Introduction
2. Results
2.1. Patient Demographics/Clinical Characteristics and SOMAscan Quality Control Results
2.2. SOMAscan Quality Control and Results by Cancer Stage
Proteins Associated with Clinical Variables of Cachexia
2.3. Functional Enrichment of Proteins
2.4. Upstream Regulators
2.5. Protein Co-Expression Analysis
3. Discussion
4. Materials and Methods
4.1. Recruitment of Study Participants
4.2. Assessment of Clinical Variables for Cachexia
4.3. Protein Measurements Using SOMAscan
4.4. Statistical Analyses
4.5. Identification of Upstream Regulators of Proteins Associated with Cachexia
4.6. Protein Co-Expression Analysis to Identify Novel Pathways Associated with Cachexia
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Characteristics | Control (n = 11) | PDAC (n = 30) | p-Value |
---|---|---|---|
Age a | 49.2 ± 14.7 | 67.1 ± 11.4 | 0.001 |
Female | 54.6 ± 12.7 | 70.5 ± 11.7 | 0.015 |
Male | 34.7 ± 8.5 | 64.2 ± 10.3 | 0.002 |
Gender b | 0.138 | ||
Female | 8 | 14 | |
Male | 3 | 16 | |
Cancer Stage | |||
Local/locally advanced | 19 | ||
Metastatic | 11 | ||
BMI (kg/m2) † a | 33.2 ± 7.8 | 28.0 ± 7.1 | 0.023 |
Female | 33.4 ± 8.8 | 26.1 ± 4.5 | 0.042 |
Male | 32.7 ± 3.8 | 29.7 ± 8.5 | 0.301 |
Change in weight (% mean) ‡ a | −0.9 ± 9.1 | 11.9 ± 8.1 | 0.001 |
Female | 0.2 ± 10.4 | −10.8 ± 8.3 | 0.013 |
Male | −4.0 ± 0.7 | −12.9 ± 7.8 | 0.129 |
Weight Loss Grade c | 0.02 | ||
Grade 0 | 3 | 3 | |
Grade 1 | 4 | 2 | |
Grade 2 | 3 | 7 | |
Grade 3 | 1 | 8 | |
Grade 4 | 0 | 9 | |
Skeletal muscle index (cm2/m2) * a | |||
Female | 51.5 ± 9.3 | 39.6 ± 4.2 | 0.013 |
Male | 59.9 ± 4.4 | 46.1 ± 12.2 | 0.1 |
Skeletal muscle density (HU) a | |||
Female | 30.8 ± 7.7 | 27.9 ± 9.5 | 0.99 |
Male | 40.3 ± 0.9 | 33.2 ± 9.8 | 0.427 |
Total Adipose Index (cm2/m2) * a | |||
Female | 183.8 ± 82.1 | 111.1 ± 52.2 | 0.140 |
Male | 177.4 ± 54.8 | 143.7 ± 83.2 | 0.301 |
Sarcopenia Status (yes/no) § c | 2/9 | 20/8 | 0.0040 |
Female | 2/6 | 6/7 | 0.399 |
Male | 0/3 | 12/6 | 0.0632 |
Information not available | - | 2 |
Protein Name | r-Value | p-Value | Protein Name | r-Value | p-Value | Protein Name | r-Value | p-Value |
---|---|---|---|---|---|---|---|---|
LYVE1 | 0.67 | 0.0001 | C5 | −0.55 | 0.0027 | TNFRSF10A | −0.52 | 0.0056 |
C7 | 0.65 | 0.0003 | SEMA6B | 0.55 | 0.0028 | KRAS | −0.52 | 0.0056 |
F2 | −0.64 | 0.0003 | PIM1 | −0.55 | 0.0031 | SPP1 | 0.52 | 0.0059 |
SLAMF6 | 0.64 | 0.0004 | HSD17B1 | −0.54 | 0.0032 | PIK3CA PIK3R1 | 0.52 | 0.0059 |
CDH15 | −0.61 | 0.0007 | SOST | −0.54 | 0.0034 | PDXK | 0.51 | 0.0063 |
LEP | −0.6 | 0.0010 | RPS7 | 0.54 | 0.0034 | TLR2 | 0.51 | 0.0064 |
ENTPD5 | −0.59 | 0.0013 | PRSS27 | −0.54 | 0.0035 | IFNAR1 | 0.51 | 0.0065 |
HSPD1 | 0.57 | 0.0018 | XPNPEP1 | 0.54 | 0.0037 | STK17B | −0.51 | 0.0065 |
GHR | −0.57 | 0.0020 | NANOG | −0.54 | 0.0038 | WFIKKN1 | −0.52 | 0.0068 |
DLL4 | 0.57 | 0.0020 | ASGR1 | 0.54 | 0.0039 | FCER2 | −0.50 | 0.0073 |
CMPK1 | −0.57 | 0.0020 | MSTN | −0.53 | 0.0040 | AHSG | −0.50 | 0.0074 |
CA10 | −0.57 | 0.0021 | LCORL | −0.53 | 0.0041 | IL1RL1 | 0.50 | 0.0075 |
LY9 | 0.56 | 0.0022 | LTA | −0.53 | 0.0042 | INHBA | 0.50 | 0.0077 |
ALB | −0.56 | 0.0025 | CRLF2 | −0.53 | 0.0044 | AFM | −0.50 | 0.0077 |
GDNF | −0.55 | 0.0026 | ABL2 | −0.53 | 0.0047 | BOC | 0.50 | 0.0078 |
SERPINA1 | 0.56 | 0.0026 | CXCL5 | −0.53 | 0.0048 |
Protein Name | r-Value | p-Value | Protein Name | r-Value | p-Value |
---|---|---|---|---|---|
GRP | 0.70 | 0.0001 | SET | 0.56 | 0.0028 |
S100A7 | 0.62 | 0.0007 | LEP | 0.56 | 0.0028 |
CCL28 | −0.61 | 0.0009 | RSPO3 | −0.56 | 0.0031 |
CFH | 0.60 | 0.0012 | WFIKKN1 | 0.54 | 0.0041 |
AFM | 0.59 | 0.0012 | LPO | −0.53 | 0.0050 |
MB | 0.59 | 0.0015 | IL1R2 | 0.53 | 0.0054 |
TYMS | 0.57 | 0.0023 | HRG | 0.52 | 0.0066 |
GHR | 0.57 | 0.0025 | HDAC8 | 0.51 | 0.0076 |
PIM1 | 0.57 | 0.0026 | MDK | −0.50 | 0.0086 |
KLK11 | −0.56 | 0.0027 |
Protein Name | r-Value | p-Value |
---|---|---|
FABP3 | −0.77 | 3.7000 × 10−6 |
COL18A1 | −0.63 | 0.0006 |
LRRTM1 | −0.61 | 0.0008 |
CFH | −0.58 | 0.0018 |
AKT2 | 0.57 | 0.0025 |
CFD | −0.57 | 0.0026 |
C5 | −0.56 | 0.0031 |
IMPDH1 | 0.56 | 0.0032 |
IFNA7 | −0.55 | 0.0034 |
IL17B | 0.53 | 0.0051 |
LILRB2 | −0.53 | 0.0052 |
FCER2 | −0.51 | 0.0073 |
SIGLEC14 | −0.51 | 0.0074 |
CLEC1B | 0.50 | 0.0086 |
Protein Name | r-Value | p-Value | Protein Name | r-Value | p-Value |
---|---|---|---|---|---|
LEP | 0.85 | 3.13 × 10−8 | Human-virus | 0.56 | 0.003 |
C5 | 0.69 | 0.0001 | CFH | 0.54 | 0.004 |
CCL28 | −0.68 | 0.0002 | TP53 | 0.54 | 0.004 |
FABP3 | 0.67 | 0.0002 | DKKL1 | 0.55 | 0.004 |
BIRC5 | 0.65 | 0.0003 | AFM | 0.55 | 0.004 |
C1S | 0.65 | 0.0003 | PLG | 0.54 | 0.005 |
KLRF1 | 0.65 | 0.0003 | SFRP1 | −0.53 | 0.006 |
PIM1 | 0.65 | 0.0003 | UBE2G2 | 0.52 | 0.006 |
KLK11 | −0.61 | 0.001 | F9 | 0.53 | 0.006 |
MDK | −0.61 | 0.001 | KLKB1 | 0.552 | 0.006 |
PRKAA1 | 0.59 | 0.001 | PTN | −0.52 | 0.007 |
HRG | 0.6 | 0.001 | LTBR | 0.51 | 0.007 |
RSPO3 | −0.58 | 0.002 | KEAP1 | −0.51 | 0.008 |
HMGN1 | 0.58 | 0.002 | APOE | 0.5 | 0.009 |
LMAN2 | 0.59 | 0.002 | CCL16 | 0.5 | 0.01 |
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Share and Cite
Narasimhan, A.; Shahda, S.; Kays, J.K.; Perkins, S.M.; Cheng, L.; Schloss, K.N.H.; Schloss, D.E.I.; Koniaris, L.G.; Zimmers, T.A. Identification of Potential Serum Protein Biomarkers and Pathways for Pancreatic Cancer Cachexia Using an Aptamer-Based Discovery Platform. Cancers 2020, 12, 3787. https://doi.org/10.3390/cancers12123787
Narasimhan A, Shahda S, Kays JK, Perkins SM, Cheng L, Schloss KNH, Schloss DEI, Koniaris LG, Zimmers TA. Identification of Potential Serum Protein Biomarkers and Pathways for Pancreatic Cancer Cachexia Using an Aptamer-Based Discovery Platform. Cancers. 2020; 12(12):3787. https://doi.org/10.3390/cancers12123787
Chicago/Turabian StyleNarasimhan, Ashok, Safi Shahda, Joshua K. Kays, Susan M. Perkins, Lijun Cheng, Katheryn N. H. Schloss, Daniel E. I. Schloss, Leonidas G. Koniaris, and Teresa A. Zimmers. 2020. "Identification of Potential Serum Protein Biomarkers and Pathways for Pancreatic Cancer Cachexia Using an Aptamer-Based Discovery Platform" Cancers 12, no. 12: 3787. https://doi.org/10.3390/cancers12123787