Protein-Based Predictive Biomarkers to Personalize Neoadjuvant Therapy for Bladder Cancer—A Systematic Review of the Current Status
Abstract
1. Introduction
2. Methods
Search Strategy
3. Results
3.1. Literature Review
3.2. Predicting Neoadjuvant Chemotherapy Response
3.3. Using IHC to Characterize Subtypes and Their Response to NAC
3.4. Cancer Stem Cell Markers as Predictors of NAC Response
3.5. Epithelial–Mesenchymal Transition (EMT) Markers as Predictors of NAC Response
3.6. Apoptosis-Related Markers and Response to NAC
3.7. Actin/Cytoskeleton Organization and Its Potential to Predict Response to NAC
3.8. Tumor-Infiltrating Immune Cells for Predicting Response to NAC
4. Discussion and Future Directions
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
References
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PMID & Reference | a Markers | Sample Size | d Study Type | Tumor Grade | T-Stage | NAC Regimen | i Clinical Outcome | j Statistical Methods | Predictive Biomarkers (p-Values) |
---|---|---|---|---|---|---|---|---|---|
36737799 [33] | KRT5, KRT6, GATA3, p53, HER2, EGFR | 60 | Single | HG | T2–T4 | f Gem+Cis; Cis ineligible Gem+Carbo | CR; OS; DFS | KM; Cox | NAC response correlates with KRT5/6 (+) (basal subtype (p = 0.045) |
34494414 [34] | KRT5, KRT6, KRT20, CD44, GATA3 | 16 | Single | Not provided | Ta–T4a | Gem + Cis | CR; PR | Descriptive | KRT20 (p = 0.013) small study |
35612672 [35] | UPII | 80 | Multi | e Not provided | T2–T4 | Not provided | OS; CSS | KM | Not significant Prediction of luminal subtype–cut-off 50% -> 90% accuracy |
33943049 [36] | KRT5, KRT6, KRT20 | 63 | Multi | LG (2); HG (61) | LG: Ta; HG tumors: T2–T4 | Gem+Cis; cis ineligible—Gem+Carbo | CR; OS | LR; KM; Cox | KRT5/6 (+)/KRT20 (−) combined marker (p = 0.037) |
34782206 [37] | 13-Marker LundTax Panel | 148 | Multi | Gx, G2, G3 | T2–T4 | Cis-based | CR; PR; NR | KM; Cox | Basal/squamous subtype: Poor response; osteopontin–subtype dependent response prediction |
37076398 [38] | c 12 markers | 208 | Single | Not provided | T2–T4 | Not provided | DFS | KM; LR; Chi-sq; FE | None significant |
34211078 [39] | ALDH1, SOX2, SSEA-4 | 269 | Multi | LG (1); HG (68); Unknown (5) | Ta, Tis, T1 = 22 T2–T4 | Gem+Cis (90% pts); Gem+Carbo (10% pts) | CR; PR | KM; Chi-sq | None significant |
31326313 [40] | E-cadherin, N-cadherin, vimentin, zeb-1, β-catenin, cofilin, phospho cofilin α-tubulin | 90 | Multi | Not provided | T2 | MVAC or Gem+Cis | OC vs. EV; CR | LR; KM; WSR; HM | NAC response prediction: N-cadherin (p = 0.027); α-tubulin (p = 0.037) |
30806186 [41] | Bcl-2 | 247 | Multi | Not provided | T2–T4 | MVAC | OS | LR; KM; Cox | Not significant |
33766713 [42] | Emmprin, Survivin, Bcl-2, CCTα | 639 | Multi | Not provided | T2–T4 | MVAC | OS | KM; Cox | CCTα (p = 0.009); CCTα (-)/Emmprin (-) better survival |
34808009 [43] | SLFN11 | 120 | Multi | LG (6); HG (44) | T2–T4 | Carbo or Cis based | OS | KM; Cox | SLFN11 (p = 0.018) |
31646091 [44] | CD8, FoxP3, CD20, PD-1, PD-L1 | 135 | Single | HG | T2–T4 | g MVAC; plus adjuvant chemotherapy | CR; PR | KM; Cox | None significant |
38092611 [45] | b proteomic digital spatial profiling–52 markers | 36 | Multi | Not provided | T2–T4 | h Gem+Cis + Immunotherapy | OS; CR; PR | KM, FE, WSR, DL | Intratumoral heterogeneity of DSP markers; certain DSP-based markers (Ki67; HER2) in a spatial context potentially predict response |
37373873 [46] | CD47 | 87 | Single | HG | T2–T4 | Cis-based | CR; PR | KM; Cox | Not significant |
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Bedore, S.; van der Eerden, J.; Boghani, F.; Patel, S.J.; Yassin, S.; Aguilar, K.; Lokeshwar, V.B. Protein-Based Predictive Biomarkers to Personalize Neoadjuvant Therapy for Bladder Cancer—A Systematic Review of the Current Status. Int. J. Mol. Sci. 2024, 25, 9899. https://doi.org/10.3390/ijms25189899
Bedore S, van der Eerden J, Boghani F, Patel SJ, Yassin S, Aguilar K, Lokeshwar VB. Protein-Based Predictive Biomarkers to Personalize Neoadjuvant Therapy for Bladder Cancer—A Systematic Review of the Current Status. International Journal of Molecular Sciences. 2024; 25(18):9899. https://doi.org/10.3390/ijms25189899
Chicago/Turabian StyleBedore, Stacy, Joshua van der Eerden, Faizan Boghani, Saloni J. Patel, Samer Yassin, Karina Aguilar, and Vinata B. Lokeshwar. 2024. "Protein-Based Predictive Biomarkers to Personalize Neoadjuvant Therapy for Bladder Cancer—A Systematic Review of the Current Status" International Journal of Molecular Sciences 25, no. 18: 9899. https://doi.org/10.3390/ijms25189899
APA StyleBedore, S., van der Eerden, J., Boghani, F., Patel, S. J., Yassin, S., Aguilar, K., & Lokeshwar, V. B. (2024). Protein-Based Predictive Biomarkers to Personalize Neoadjuvant Therapy for Bladder Cancer—A Systematic Review of the Current Status. International Journal of Molecular Sciences, 25(18), 9899. https://doi.org/10.3390/ijms25189899