Machine-Learning Analysis of Serum Proteomics in Neuropathic Pain after Nerve Injury in Breast Cancer Surgery Points at Chemokine Signaling via SIRT2 Regulation Article Swipe
Jörn Lötsch
,
Laura Mustonen
,
Hanna Harno
,
Eija Kalso
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.3390/ijms23073488
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.3390/ijms23073488
Background: Persistent postsurgical neuropathic pain (PPSNP) can occur after intraoperative damage to somatosensory nerves, with a prevalence of 29–57% in breast cancer surgery. Proteomics is an active research field in neuropathic pain and the first results support its utility for establishing diagnoses or finding therapy strategies. Methods: 57 women (30 non-PPSNP/27 PPSNP) who had experienced a surgeon-verified intercostobrachial nerve injury during breast cancer surgery, were examined for patterns in 74 serum proteomic markers that allowed discrimination between subgroups with or without PPSNP. Serum samples were obtained both before and after surgery. Results: Unsupervised data analyses, including principal component analysis and self-organizing maps of artificial neurons, revealed patterns that supported a data structure consistent with pain-related subgroup (non-PPSPN vs. PPSNP) separation. Subsequent supervised machine learning-based analyses revealed 19 proteins (CD244, SIRT2, CCL28, CXCL9, CCL20, CCL3, IL.10RA, MCP.1, TRAIL, CCL25, IL10, uPA, CCL4, DNER, STAMPB, CCL23, CST5, CCL11, FGF.23) that were informative for subgroup separation. In cross-validated training and testing of six different machine-learned algorithms, subgroup assignment was significantly better than chance, whereas this was not possible when training the algorithms with randomly permuted data or with the protein markers not selected. In particular, sirtuin 2 emerged as a key protein, presenting both before and after breast cancer treatments in the PPSNP compared with the non-PPSNP subgroup. Conclusions: The identified proteins play important roles in immune processes such as cell migration, chemotaxis, and cytokine-signaling. They also have considerable overlap with currently known targets of approved or investigational drugs. Taken together, several lines of unsupervised and supervised analyses pointed to structures in serum proteomics data, obtained before and after breast cancer surgery, that relate to neuroinflammatory processes associated with the development of neuropathic pain after an intraoperative nerve lesion.
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- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3390/ijms23073488
- https://www.mdpi.com/1422-0067/23/7/3488/pdf?version=1648117507
- OA Status
- gold
- Cited By
- 14
- References
- 130
- Related Works
- 10
- OpenAlex ID
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- OpenAlex ID
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https://openalex.org/W4221108815Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.3390/ijms23073488Digital Object Identifier
- Title
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Machine-Learning Analysis of Serum Proteomics in Neuropathic Pain after Nerve Injury in Breast Cancer Surgery Points at Chemokine Signaling via SIRT2 RegulationWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2022Year of publication
- Publication date
-
2022-03-23Full publication date if available
- Authors
-
Jörn Lötsch, Laura Mustonen, Hanna Harno, Eija KalsoList of authors in order
- Landing page
-
https://doi.org/10.3390/ijms23073488Publisher landing page
- PDF URL
-
https://www.mdpi.com/1422-0067/23/7/3488/pdf?version=1648117507Direct link to full text PDF
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YesWhether a free full text is available
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goldOpen access status per OpenAlex
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https://www.mdpi.com/1422-0067/23/7/3488/pdf?version=1648117507Direct OA link when available
- Concepts
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Breast cancer, Neuropathic pain, Medicine, Chemokine, Nerve injury, Proteomics, Bioinformatics, Cancer, Inflammation, Internal medicine, Surgery, Anesthesia, Biology, Gene, BiochemistryTop concepts (fields/topics) attached by OpenAlex
- Cited by
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14Total citation count in OpenAlex
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2025: 4, 2024: 7, 2023: 3Per-year citation counts (last 5 years)
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130Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.of | 17, 102, 158, 241, 250, 278 |
| abstract_inverted_index.or | 42, 79, 183, 243 |
| abstract_inverted_index.to | 11, 256, 271 |
| abstract_inverted_index.(30 | 49 |
| abstract_inverted_index.The | 216 |
| abstract_inverted_index.and | 32, 88, 99, 156, 202, 230, 252, 264 |
| abstract_inverted_index.can | 6 |
| abstract_inverted_index.for | 39, 66, 150 |
| abstract_inverted_index.had | 53 |
| abstract_inverted_index.its | 37 |
| abstract_inverted_index.key | 197 |
| abstract_inverted_index.not | 173, 188 |
| abstract_inverted_index.six | 159 |
| abstract_inverted_index.the | 33, 177, 185, 208, 212, 276 |
| abstract_inverted_index.vs. | 117 |
| abstract_inverted_index.was | 165, 172 |
| abstract_inverted_index.who | 52 |
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| abstract_inverted_index.also | 233 |
| abstract_inverted_index.both | 86, 200 |
| abstract_inverted_index.cell | 227 |
| abstract_inverted_index.data | 93, 110, 182 |
| abstract_inverted_index.have | 234 |
| abstract_inverted_index.maps | 101 |
| abstract_inverted_index.pain | 4, 31, 280 |
| abstract_inverted_index.play | 219 |
| abstract_inverted_index.such | 225 |
| abstract_inverted_index.than | 168 |
| abstract_inverted_index.that | 73, 107, 147, 269 |
| abstract_inverted_index.this | 171 |
| abstract_inverted_index.uPA, | 139 |
| abstract_inverted_index.were | 64, 84, 148 |
| abstract_inverted_index.when | 175 |
| abstract_inverted_index.with | 14, 78, 113, 179, 184, 211, 237, 275 |
| abstract_inverted_index.CCL3, | 133 |
| abstract_inverted_index.CCL4, | 140 |
| abstract_inverted_index.CST5, | 144 |
| abstract_inverted_index.DNER, | 141 |
| abstract_inverted_index.IL10, | 138 |
| abstract_inverted_index.PPSNP | 209 |
| abstract_inverted_index.Serum | 82 |
| abstract_inverted_index.Taken | 246 |
| abstract_inverted_index.after | 8, 89, 203, 265, 281 |
| abstract_inverted_index.data, | 261 |
| abstract_inverted_index.field | 28 |
| abstract_inverted_index.first | 34 |
| abstract_inverted_index.known | 239 |
| abstract_inverted_index.lines | 249 |
| abstract_inverted_index.nerve | 58, 284 |
| abstract_inverted_index.occur | 7 |
| abstract_inverted_index.roles | 221 |
| abstract_inverted_index.serum | 70, 259 |
| abstract_inverted_index.women | 48 |
| abstract_inverted_index.CCL11, | 145 |
| abstract_inverted_index.CCL20, | 132 |
| abstract_inverted_index.CCL23, | 143 |
| abstract_inverted_index.CCL25, | 137 |
| abstract_inverted_index.CCL28, | 130 |
| abstract_inverted_index.CXCL9, | 131 |
| abstract_inverted_index.MCP.1, | 135 |
| abstract_inverted_index.PPSNP) | 51, 118 |
| abstract_inverted_index.PPSNP. | 81 |
| abstract_inverted_index.SIRT2, | 129 |
| abstract_inverted_index.TRAIL, | 136 |
| abstract_inverted_index.active | 26 |
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| abstract_inverted_index.better | 167 |
| abstract_inverted_index.breast | 20, 61, 204, 266 |
| abstract_inverted_index.cancer | 21, 62, 205, 267 |
| abstract_inverted_index.damage | 10 |
| abstract_inverted_index.drugs. | 245 |
| abstract_inverted_index.during | 60 |
| abstract_inverted_index.immune | 223 |
| abstract_inverted_index.injury | 59 |
| abstract_inverted_index.relate | 270 |
| abstract_inverted_index.(CD244, | 128 |
| abstract_inverted_index.(PPSNP) | 5 |
| abstract_inverted_index.FGF.23) | 146 |
| abstract_inverted_index.STAMPB, | 142 |
| abstract_inverted_index.allowed | 74 |
| abstract_inverted_index.between | 76 |
| abstract_inverted_index.chance, | 169 |
| abstract_inverted_index.emerged | 194 |
| abstract_inverted_index.finding | 43 |
| abstract_inverted_index.lesion. | 285 |
| abstract_inverted_index.machine | 122 |
| abstract_inverted_index.markers | 72, 187 |
| abstract_inverted_index.nerves, | 13 |
| abstract_inverted_index.overlap | 236 |
| abstract_inverted_index.pointed | 255 |
| abstract_inverted_index.protein | 186 |
| abstract_inverted_index.results | 35 |
| abstract_inverted_index.samples | 83 |
| abstract_inverted_index.several | 248 |
| abstract_inverted_index.sirtuin | 192 |
| abstract_inverted_index.support | 36 |
| abstract_inverted_index.targets | 240 |
| abstract_inverted_index.testing | 157 |
| abstract_inverted_index.therapy | 44 |
| abstract_inverted_index.utility | 38 |
| abstract_inverted_index.whereas | 170 |
| abstract_inverted_index.without | 80 |
| abstract_inverted_index.29–57% | 18 |
| abstract_inverted_index.IL.10RA, | 134 |
| abstract_inverted_index.Methods: | 46 |
| abstract_inverted_index.Results: | 91 |
| abstract_inverted_index.analyses | 124, 254 |
| abstract_inverted_index.analysis | 98 |
| abstract_inverted_index.approved | 242 |
| abstract_inverted_index.compared | 210 |
| abstract_inverted_index.examined | 65 |
| abstract_inverted_index.neurons, | 104 |
| abstract_inverted_index.obtained | 85, 262 |
| abstract_inverted_index.patterns | 67, 106 |
| abstract_inverted_index.permuted | 181 |
| abstract_inverted_index.possible | 174 |
| abstract_inverted_index.protein, | 198 |
| abstract_inverted_index.proteins | 127, 218 |
| abstract_inverted_index.randomly | 180 |
| abstract_inverted_index.research | 27 |
| abstract_inverted_index.revealed | 105, 125 |
| abstract_inverted_index.subgroup | 115, 151, 163 |
| abstract_inverted_index.surgery, | 63, 268 |
| abstract_inverted_index.surgery. | 22, 90 |
| abstract_inverted_index.training | 155, 176 |
| abstract_inverted_index.analyses, | 94 |
| abstract_inverted_index.component | 97 |
| abstract_inverted_index.currently | 238 |
| abstract_inverted_index.diagnoses | 41 |
| abstract_inverted_index.different | 160 |
| abstract_inverted_index.important | 220 |
| abstract_inverted_index.including | 95 |
| abstract_inverted_index.non-PPSNP | 213 |
| abstract_inverted_index.principal | 96 |
| abstract_inverted_index.processes | 224, 273 |
| abstract_inverted_index.proteomic | 71 |
| abstract_inverted_index.selected. | 189 |
| abstract_inverted_index.structure | 111 |
| abstract_inverted_index.subgroup. | 214 |
| abstract_inverted_index.subgroups | 77 |
| abstract_inverted_index.supported | 108 |
| abstract_inverted_index.together, | 247 |
| abstract_inverted_index.(non-PPSPN | 116 |
| abstract_inverted_index.Persistent | 1 |
| abstract_inverted_index.Proteomics | 23 |
| abstract_inverted_index.Subsequent | 120 |
| abstract_inverted_index.algorithms | 178 |
| abstract_inverted_index.artificial | 103 |
| abstract_inverted_index.assignment | 164 |
| abstract_inverted_index.associated | 274 |
| abstract_inverted_index.consistent | 112 |
| abstract_inverted_index.identified | 217 |
| abstract_inverted_index.migration, | 228 |
| abstract_inverted_index.presenting | 199 |
| abstract_inverted_index.prevalence | 16 |
| abstract_inverted_index.proteomics | 260 |
| abstract_inverted_index.structures | 257 |
| abstract_inverted_index.supervised | 121, 253 |
| abstract_inverted_index.treatments | 206 |
| abstract_inverted_index.Background: | 0 |
| abstract_inverted_index.algorithms, | 162 |
| abstract_inverted_index.chemotaxis, | 229 |
| abstract_inverted_index.development | 277 |
| abstract_inverted_index.experienced | 54 |
| abstract_inverted_index.informative | 149 |
| abstract_inverted_index.neuropathic | 3, 30, 279 |
| abstract_inverted_index.particular, | 191 |
| abstract_inverted_index.separation. | 119, 152 |
| abstract_inverted_index.strategies. | 45 |
| abstract_inverted_index.Conclusions: | 215 |
| abstract_inverted_index.Unsupervised | 92 |
| abstract_inverted_index.considerable | 235 |
| abstract_inverted_index.establishing | 40 |
| abstract_inverted_index.non-PPSNP/27 | 50 |
| abstract_inverted_index.pain-related | 114 |
| abstract_inverted_index.postsurgical | 2 |
| abstract_inverted_index.unsupervised | 251 |
| abstract_inverted_index.significantly | 166 |
| abstract_inverted_index.somatosensory | 12 |
| abstract_inverted_index.discrimination | 75 |
| abstract_inverted_index.intraoperative | 9, 283 |
| abstract_inverted_index.learning-based | 123 |
| abstract_inverted_index.cross-validated | 154 |
| abstract_inverted_index.investigational | 244 |
| abstract_inverted_index.machine-learned | 161 |
| abstract_inverted_index.self-organizing | 100 |
| abstract_inverted_index.surgeon-verified | 56 |
| abstract_inverted_index.neuroinflammatory | 272 |
| abstract_inverted_index.intercostobrachial | 57 |
| abstract_inverted_index.cytokine-signaling. | 231 |
| cited_by_percentile_year.max | 99 |
| cited_by_percentile_year.min | 96 |
| corresponding_author_ids | https://openalex.org/A5017400006 |
| countries_distinct_count | 2 |
| institutions_distinct_count | 4 |
| corresponding_institution_ids | https://openalex.org/I114090438, https://openalex.org/I4210107844 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/5 |
| sustainable_development_goals[0].score | 0.44999998807907104 |
| sustainable_development_goals[0].display_name | Gender equality |
| citation_normalized_percentile.value | 0.84734066 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |