Leptin and Adiponectin as Immunohistochemical Biomarkers in Colorectal Cancer: Publication Trends and Research Advances
Source abstract
Abstract
Background: Leptin and adiponectin play a key role in obesity-associated malignancy, particularly in colorectal cancer (CRC). Immunohistochemical (IHC) evaluation of these adipokines may offer valuable prognostic insights in CRC. This study aimed to analyze global publication trends and summarize current knowledge on the potential of these hormones as IHC biomarkers in CRC. Methods: A problem-oriented bibliometric analysis, including publications from 2000 to 2025, was performed across the MEDLINE and Scopus databases. In parallel, a literature review was conducted to present the biological and clinical relevance of these adipokines in CRC. Results and Discussion: A total of 101 publications were identified. Scopus indexed substantially more studies than MEDLINE. The journals Cancer Research, Journal of BUON, Cells, BMC Cancer, and Asian Pacific Journal of Cancer Prevention were identified as the core journals publishing on this topic over the 25-year period. The leading countries were China and the USA. A review of the literature showed that adiponectin is a promising prognostic marker, while leptin appears to be a better indicator of disease progression. Conclusions: IHC research on leptin and adiponectin in CRC is a promising but still underexplored area. Their integration with routine molecular assessment has the potential to improve patient stratification.
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Research context
OpenAlex topics: Adipokines, Inflammation, and Metabolic Diseases · Regulation of Appetite and Obesity · Cancer Risks and Factors
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of Biology, Faculty of Pharmacy, Medical University “Prof. Dr. Paraskev Stoyanov”, 9000 Varna, Bulgaria
Department of Biochemistry, Molecular Medicine and Nutrigenomics, Faculty of Pharmacy, Medical University “Prof. Dr. Paraskev Stoyanov”, 9000 Varna, Bulgaria
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Medical University “Prof. Dr. Paraskev Stoyanov”, 9000 Varna, Bulgaria
Department of Obstetrics and Gynecology, Faculty of Medicine, Medical University “Prof. Dr. Paraskev Stoyanov”, 9000 Varna, Bulgaria
References (72)
Show source-provided references
1. Adiponectin receptor agonist suppresses human colorectal cancer10.21873/anticanres.17670 ↗
2. Vahed, I.E., Moshgelgosha, M., Kor, A., Minadi, M., Ebrahimi, F., Azhdarian, A., Arjmandi, M., Alamdar, A., Zare, M., and Shabani, N. (2025). The role of adiponectin and leptin in colorectal cancer and adenoma: A systematic review and meta-analysis. BMC Cancer, 25.10.1186/s12885-025-14362-y ↗
3. Zhang, X., Han, Q.Y., Zhang, J.G., Lin, J., Yan, W.H., and Lin, A. (2025). Human leukocyte antigen-G isoform HLA-G2/6, but not HLA-G1/4/5, is an independent indicator of poor survival in patients with colorectal cancer. Front. Immunol., 16.10.3389/fimmu.2025.1672144 ↗
4. Yue, B., Lu, Z., Zong, D., Hu, Y., and Yang, Z. (2025). Global, regional, and national burden of early-onset and late-onset colorectal cancer attributable to high body-mass index from 1990 to 2021: A trend analysis and forecasts up to 2040 based on the Global Burden of Disease Study 2021. BMC Gastroenterol., 25.10.1186/s12876-025-04432-7 ↗
5. Wu, S., Zhang, Y., Lin, Z., and Wei, M. (2025). Global burden of colorectal cancer in 2022 and projections to 2050: Incidence and mortality estimates from GLOBOCAN. BMC Cancer, 25.10.1186/s12885-025-15138-0 ↗
6. Prognostic significance of serum adipokine levels in colorectal cancer patients
7. Pham, D.V., and Park, P.H. (2021). Tumor metabolic reprogramming by adipokines as a critical driver of obesity-associated cancer progression. Int. J. Mol. Sci., 22.10.3390/ijms22031444 ↗
8. Leptin acts as a growth factor for colorectal tumours at stages subsequent to tumour initiation in murine colon carcinogenesis10.1136/gut.2010.235754 ↗
9. Adiponectin and colorectal cancer10.1007/s00595-016-1334-4 ↗
10. Pathological features and prognostication in colorectal cancer10.3390/curroncol28060447 ↗
11. The consensus molecular subtypes of colorectal cancer10.1038/nm.3967 ↗
12. Profiling the heterogeneity of colorectal cancer consensus molecular subtypes using spatial transcriptomics10.1038/s41698-023-00488-4 ↗
13. Practical and robust identification of molecular subtypes in colorectal cancer by immunohistochemistry10.1158/1078-0432.CCR-16-0680 ↗
14. A modified protein marker panel to identify four consensus molecular subtypes in colorectal cancer using immunohistochemistry10.1016/j.prp.2021.153379 ↗
15. Adipobiology: A bibliometric view to its increasing significance10.14748/bmr.v17.87 ↗
16. Institutionalization patterns in breast cancer immunohistochemistry10.5272/jimab.2022281.4211 ↗
17. Dynamic institutionalization of research in the field of colorectal tumour markers
18. Role of Dysregulated Expression of Leptin and Leptin Receptors in Colorectal Carcinogenesis10.1007/s13277-013-1166-4 ↗
19. Leptin-Induced Signaling Pathways in Cancer Cell Migration and Invasion10.1007/s13402-019-00428-0 ↗
20. Metallopanstimulin-1 (MPS-1) Mediates the Promotion Effect of Leptin on Colorectal Cancer through Activation of JNK/c-Jun Signaling Pathway10.1038/s41419-019-1911-8 ↗
21. Socol, C.T., Chira, A., Martinez-Sanchez, M.A., Nuñez-Sanchez, M.A., Maerescu, C.M., Mierlita, D., Rusu, A.V., Ruiz-Alcaraz, A.J., Trif, M., and Ramos-Molina, B. (2022). Leptin Signaling in Obesity and Colorectal Cancer. Int. J. Mol. Sci., 23.10.3390/ijms23094713 ↗
22. Role of the Long Form Leptin Receptor and of the STAT3 Signaling Pathway in Colorectal Cancer Progression
23. Importance of Circulating Leptin and Adiponectin in the Causal Pathways Between Obesity and the Development of Colorectal Cancer in Japanese Men10.2188/jea.JE20230148 ↗
24. Kafeel, S., Palmiero, G., Salzillo, A., Ragone, A., Naviglio, S., and Sapio, L. (2025). Unravelling the Adiponectin Hallmark and Exploring the Therapeutic Potential of Its Receptor Agonists in Cancer Metabolic Reprogramming. Biomolecules, 15.10.3390/biom15060820 ↗
25. The Bifurcated Role of Adiponectin in Colorectal Cancer10.1016/j.lfs.2021.119524 ↗
26. Jones, A.N., Scheurlen, K.M., Macleod, A., Simon, H.L., and Galandiuk, S. (2024). Obesity and Inflammatory Factors in the Progression of Early-Onset Colorectal Cancer. Cancers, 16.10.3390/cancers16071403 ↗
27. Kounatidis, D., Vallianou, N.G., Karampela, I., Rebelos, E., Kouveletsou, M., Dalopoulos, V., Koufopoulos, P., Diakoumopoulou, E., Tentolouris, N., and Dalamaga, M. (2024). Anti-Diabetic Therapies and Cancer: From Bench to Bedside. Biomolecules, 14.10.3390/biom14111479 ↗
28. Scheurlen, K.M. (2022). The Role of Obesity in Macrophage-Mediated Mechanisms Promoting Early-Onset Colon Cancer. [Doctoral Dissertation, University of Louisville].
29. Overexpression of the obesity hormone leptin in human colorectal cancer10.1136/jcp.2006.041004 ↗
30. Leptin expression correlates with favorable clinicopathologic phenotype and better prognosis in colorectal adenocarcinoma10.1245/s10434-008-0221-7 ↗
31. Prognostic significance of tissue leptin expression in colorectal cancer patients10.3393/ac.2015.31.6.222 ↗
32. Expression of leptin in colorectal adenocarcinoma showed significant different survival patterns associated with tumor size, lymphovascular invasion, distant metastasis, local recurrence, and relapse of disease in the western province of Saudi Arabia10.1097/MD.0000000000012052 ↗
33. Leptin overexpression as a poor prognostic factor for colorectal cancer10.1155/2020/7532514 ↗
34. Expression of leptin and leptin receptors in colorectal cancer—An immunohistochemical study10.7717/peerj.7624 ↗
35. Evaluation of circulating leptin and its receptor (Ob-R) tissue expression in colorectal cancer, a report from North of Iran10.30699/ijp.2023.1983482.3041 ↗
36. Chludzińska-Kasperuk, S., Lewko, J., Sierżantowicz, R., Krajewska-Kułak, E., and Reszeć-Giełażyn, J. (2023). The effect of serum leptin concentration and leptin receptor expression on colorectal cancer. Int. J. Environ. Res. Public Health, 20.10.3390/ijerph20064951 ↗
37. Correlation of leptin and adiponectin receptor expression with clinicopathological parameters in colorectal carcinoma—A cross-sectional prospective study10.1590/s0004-2803.24612024-016 ↗
38. Evaluation of the prognostic role of leptin and cyclin D1 expression in colorectal cancer
39. Adiponectin receptor expression is elevated in colorectal carcinomas but not in gastrointestinal stromal tumors10.1677/ERC-07-0197 ↗
40. Adiponectin immunohistochemical expression in colorectal cancer and its correlation with histological grade and tumour microvessel density10.1080/00313020903071553 ↗
41. Adiponectin and adiponectin receptor in relation to colorectal cancer progression10.1002/ijc.25301 ↗
42. Adipocytokines as new promising markers of colorectal tumors: Adiponectin for colorectal adenoma, and resistin and visfatin for colorectal cancer10.1111/j.1349-7006.2010.01518.x ↗
43. Serum adiponectin levels and tissue expression of adiponectin receptors are associated with risk, stage, and grade of colorectal cancer10.1016/j.metabol.2011.03.020 ↗
44. Adiponectin levels in patients with colorectal cancer and adenoma: A meta-analysis10.1097/CEJ.0b013e32834c9b55 ↗
45. Clinical significance of adiponectin expression in colon cancer patients10.4103/0973-1482.136634 ↗
46. Globular adiponectin and its downstream target genes are up-regulated locally in human colorectal tumors: Ex vivo and in vitro studies10.1016/j.metabol.2014.02.001 ↗
47. Circulating adiponectin levels in various malignancies: An updated meta-analysis of 107 studies10.18632/oncotarget.8932 ↗
48. Associations of adiponectin receptor 2 (AdipoR2) gene polymorphisms and AdipoR2 protein expression levels with the risk of colorectal cancer: A case-control study10.3892/mmr.2017.7115 ↗
49. Differential Diagnostic and Functional Role of the Multi-Marker Phenotype CDX2/CK20/CK7 in Colorectal Cancer Stratified by Mismatch Repair Status10.1038/modpathol.2008.117 ↗
50. Immunohistochemical Expression of CK20, CK7, and CDX2 in Colorectal Carcinoma in Correlation with Pathomorphological Characteristics10.3897/folmed.64.e60950 ↗
51. CDX2, a Highly Sensitive and Specific Marker of Adenocarcinomas of Intestinal Origin: An Immunohistochemical Survey of 476 Primary and Metastatic Carcinomas10.1097/00000478-200303000-00003 ↗
52. Choi, H.B., Pyo, J.-S., Son, S., Kim, K., and Kang, G. (2022). Diagnostic and Prognostic Roles of CDX2 Immunohistochemical Expression in Colorectal Cancer: A Meta-Analysis. Diagnostics, 12.10.3390/diagnostics12030757 ↗
53. Identifying Mismatch Repair-Deficient Colon Cancer: Near-Perfect Concordance between Immunohistochemistry and Microsatellite Instability Testing in a Large, Population-Based Series10.1111/his.14233 ↗
54. Predictive and Prognostic Implications of Microsatellite Instability and Mismatch Repair Deficiency in Carcinomas of the Gastrointestinal Tract, Liver, and Pancreas10.21037/pcm.2019.09.03 ↗
55. Immunohistochemical Phenotype of Colorectal Carcinoma in Patients with KRAS Mutation and Mismatch Repair Status10.3897/folmed.65.e81334 ↗
56. HER2 Overexpression/Amplification Status in Colorectal Cancer: A Comparison between Immunohistochemistry and Fluorescence In Situ Hybridization Using Five Different Immunohistochemical Scoring Criteria10.1007/s00432-022-04230-8 ↗
57. Prognostic Role of Ki-67 in Colorectal Carcinoma: Development and Evaluation of Machine Learning Prediction Models10.5306/wjco.v16.i8.107306 ↗
58. Elevated CD163+/CD68+ Ratio at Tumor Invasive Front Is Closely Associated with Aggressive Phenotype and Poor Prognosis in Colorectal Cancer10.7150/ijbs.29836 ↗
59. Expression of Vascular Endothelial Growth Factor (VEGF) in Colorectal Adenoma and Carcinoma in a Tertiary Care Center
60. β2-Microglobulin Expression Is Associated with Aggressive Histology, Activated Tumor Immune Milieu, and Outcome in Colon Carcinoma10.1093/ajcp/aqae066 ↗
61. Zhang, W., Song, Z., Zhang, B., Wang, J., Guo, Q., Sun, Z., and Tang, H. (2020). Multiplex immunohistochemistry indicates biomarkers in colorectal cancer. Res. Sq.10.21203/rs.3.rs-105338/v1 ↗
62. Identification of Biomarkers in Colorectal Cancer Using a Multiplex Immunohistochemistry Technology
63. Multispectral imaging reveals hyper active TGF-β signaling in colorectal cancer10.1080/15384047.2017.1395116 ↗
64. Image-based consensus molecular subtype (imCMS) classification of colorectal cancer using deep learning10.1136/gutjnl-2019-319866 ↗
65. Deep learning for colon cancer histopathological images analysis10.1016/j.compbiomed.2021.104730 ↗
66. Davri, A., Birbas, E., Kanavos, T., Ntritsos, G., Giannakeas, N., Tzallas, A., and Batistatou, A. (2022). Deep Learning on Histopathological Images for Colorectal Cancer Diagnosis: A Systematic Review. Diagnostics, 12.10.3390/diagnostics12040837 ↗
67. Alboaneen, D., Alqarni, R., Alqahtani, S., Alrashidi, M., Alhuda, R., Alyahyan, E., and Alshammari, T. (2023). Predicting Colorectal Cancer Using Machine and Deep Learning Algorithms: Challenges and Opportunities. Big Data Cogn. Comput., 7.10.3390/bdcc7020074 ↗
68. Current mechanisms in obesity and tumor progression
69. Obesity and colorectal cancer: Role of adipokines in tumor initiation and progression10.3748/wjg.v20.i18.5177 ↗
70. Adiponectin Blocks Multiple Signaling Cascades Associated with Leptin-Induced Cell Proliferation in ApcMin/+ Colon Epithelial Cells10.1002/ijc.23436 ↗
71. Interaction between Adiponectin and Leptin Influences the Risk of Colorectal Adenoma10.1158/0008-5472.CAN-10-0178 ↗
72. Multimodal analysis of whole slide images in colorectal cancer10.1038/s41746-025-02095-y ↗