The cluster of differentiation 47 expression in rectal cancer and efficacy of neoadjuvant therapies

Öz

Aim: To investigate the relationship between CD47 expression levels, clinicopathological features, and survival in rectal cancer. Material and Methods: It was designed as a retrospective case-control study. CD47 was analyzed in tumor tissue from patients with stage II and III rectal cancer who received neoadjuvant treatment. Patients were classified as negative, low, or high based on the CD47 H score. The pathological features of the disease, responses to neoadjuvant treatment, and overall survival were examined in relation to CD47. Results: There were CD47 negative (n = 19, 31%), low (n = 18, 30%), and high (n = 24, 39%) patients. CD47 positivity was more common in female patients (p = 0.023). No significant differences were observed between the groups regarding relapse (p = 0.822), tumor location (p = 0.379), T stage (p = 0.360), preoperative lymph node status (p = 0.332), tumor grade (p = 0.801), perineural invasion (PNI) (p = 0.160), lymphovascular invasion (LVI) (p = 0.294), budding (p = 0.043), CEA level (p = 0.413), neoadjuvant treatment type (p = 0.650), T downstaging (p = 8.39), N downstaging (p = 0.530), surgery type (p = 0.717), pathological complete response (p = 0.747), tumor regression score ( p= 0.836), positive surgical margin (p = 0.309), or (p = 0.028). The 5-year OS was 88% for patients with negative CD47, 74% for those with low CD47, and 57% for high CD47 (p=0.035). Conclusion: Pretreatment CD47 score is important in terms of survival and prognosis in rectal cancer. The function of CD47 is more complex and needs to be further studied.

Anahtar Kelimeler

• rectal cancer
• CD47
• prognosis
• survival

Rektal kanserde farklılaşma kümesi 47 ekspresyonu ve neoadjuvan tedavilerin etkinliği

Öz

Amaç: Rektum kanserinde CD47 ekspresyon düzeyinin klinikopatolojik özellikler ve sağkalım ile ilişkisini araştırmak. Gereç ve Yöntemler: Retrospektif bir vaka-kontrol çalışması olarak tasarlandı. CD47 ekspresyonu, neoadjuvan tedavi alan evre II ve III rektum kanseri hastalarının tümör dokusundan çalışıldı. Hastalar CD47 H skoruna göre negatif, düşük veya yüksek olarak kategorize edildi. Hastalığın patolojik özellikleri, neoadjuvan tedaviye yanıtlar ve genel sağkalım CD47 ile ilişkili olarak incelendi. Bulgular: CD47 negatif (n = 19, %31), düşük (n = 18, %30) ve yüksek (n = 24, %39) hastalar vardı. CD47 pozitifliği kadın hastalarda daha sıktı (p = 0.023). Gruplar arasında nüks (p = 0.822), tümör lokalizasyonu (p = 0.379), T evresi ( p= 0.360), preoperatif lenf nodu durumu (p=0.332), tümör gradesi (p = 0.801), perinöral invazyon (PNİ) (p = 0.160), lenfovasküler invazyon (LVİ) (p = 0. 294), tomurcuklanma (p=0.043), CEA düzeyi (p = 0.413), neoadjuvan tedavi tipi (p=0.650), T evre azalması (p = 8.39), N evre azalması (p = 0.530), cerrahi tipi (p = 0.717), patolojik tam yanıt (p = 0.747), tümör regresyon skoru (p=0.836), pozitif cerrahi sınır (0.309) (p = 0.028) bakımından anlamlı fark yoktu. 5 yıllık OS, negatif CD47 için %88, düşük CD47 için %74 ve yüksek CD47 için %57 idi (p = 0.035). Sonuç: Tedavi öncesi CD47 skoru rektum kanserinde sağkalım ve prognoz açısından önemlidir. CD47'nin işlevi daha karmaşıktır ve daha fazla çalışılması gerekmektedir.

Anahtar Kelimeler

• rektum kanseri
• CD47
• prognoz
• sağkalım

Kaynakça

1. Siegel RL, Wagle NS, Cercek A, Smith RA, Jemal A. Colorectal cancer statistics, 2023. CA Cancer J Clin. 2023;73:233-254.
2. Kokelaar RF, Evans MD, Davies M, Harris DA, Beynon J. Locally advanced rectal cancer: management challenges. Onco Targets Ther 2016;9:6265-6272.
3. Folkesson J, Birgisson H, Pahlman L, Cedermark B, Glimelius B, Gunnarsson U. Swedish Rectal Cancer Trial: long lasting benefits from radiotherapy on survival and local recurrence rate. J Clin Oncol 2005;23:5644-50.
4. Kapiteijn E, Marijnen CA, Nagtegaal ID, Putter H, Steup WH, Wiggers T et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med 2001; 345: 638-646.
5. Daprà V, Airoldi M, Bartolini M, et al. Total neoadjuvant treatment for locally advanced rectal cancer patients: where do we stand? Int J Mol Sci 2023;24:12159.
6. Peng Y, Qiu B, Tan F, et al. TIGIT/CD47 dual high expression predicts prognosis and is associated with immunotherapy response in lung squamous cell carcinoma. Thoracic Cancer 2022;13:2014-23.
7. Shi M, Gu Y, Jin K et al. CD47 expression in gastric cancer clinical correlates and association with macrophage infiltration. Cancer Immunology, Immunotherapy 2021;70:1831-40.
8. Xing L, Wang Z, Feng Y et al. The biological roles of CD47 in ovarian cancer progression. Cancer Immunology, Immunotherapy 2024;73:145.

9. Yüceer RO, Aydın S, Gelir I, Koc T, Tuncer E, Ucar M. Exploring the Prognostic Role of Trop-2, CD47, and CD163 Expression Levels on Survival Outcomes in Patients with Triple-Negative Breast Cancer. Diagnostics 2025;15:232.
10. Biller LH, Schrag D. Diagnosis and treatment of metastatic colorectal cancer: a review. Jama 2021;325:669-85.
11. Hu T, Liu H, Liang Z et al. Tumor-intrinsic CD47 signal regulates glycolysis and promotes colorectal cancer cell growth and metastasis. Theranostics 2020;10:4056.
12. Chen Y, Klingen TA, Aas H, Wik E, Akslen LA. CD47 and CD68 expression in breast cancer is associated with tumor‐infiltrating lymphocytes, blood vessel invasion, detection mode, and prognosis. The Journal of Pathology: Clin Res 2023;9:151-64.
13. Hu J, Xiao Q, Dong M, Guo D, Wu X, Wang B. Glioblastoma immunotherapy targeting the innate immune checkpoint CD47-SIRPα axis. Front Immunol. 2020;11:593219.
14. Li Z, Li Y, Gao J, et al. The role of CD47-SIRPα immune checkpoint in tumor immune evasion and innate immunotherapy. Life Sci 2021;273:119150.
15. Lian S, Xie R, Ye Y, Xie X, Li S, Lu Y et al. Simultaneous blocking of CD47 and PD-L1 increases innate and adaptive cancer immune responses and cytokine release. EBioMed 2019;42:281-95.
16. Yang Y, Yang Z, Yang Y. Potential role of CD47-directed bispecific antibodies in cancer immunotherapy. Front Immunol 2021;12:686031.
17. Yu W-B, Ye Z-H, Chen X, Shi J-J, Lu J-J. The development of small-molecule inhibitors targeting CD47. Drug Discovery Today 2021;26:561-8.
18. Weiser MR. AJCC 8th edition: colorectal cancer. Ann Surg Oncol 2018;25:1454-5.
19. Kim H, Jee S, Kim Y, Sim J, Bang S, Son HK, et al. Correlation of CD47 expression with adverse clinicopathologic features and an unfavorable prognosis in colorectal adenocarcinoma. Diagnostics 2021;11:668.
20. Arai H, Gandhi N, Battaglin F, Wang J, Algaze S, Jayachandran P et al. Role of CD47 gene expression in colorectal cancer: a comprehensive molecular profiling study. J ImmunoTher Cancer 2024;12:e010326.
21. Xu Y, Jiang P, Xu Z, Ye H. Opportunities and challenges for anti-CD47 antibodies in hematological malignancies. Front Immunol 2024;15:1348852.
22. Guinney J, Dienstmann R, Wang X, De Reynies A, Schlicker A, Soneson C et al. The consensus molecular subtypes of colorectal cancer. Nature Med2015;21:1350-6.
23. Oh H-H, Park Y-L, Park S-Y,et al. CD47 mediates the progression of colorectal cancer by inducing tumor cell apoptosis and angiogenesis. PatholRes Practice 2022;240:154220.
24. Tian Q-S, Zhang C, Bao Z-J, Pei Z. The role of CD47 in immune escape of colon cancer and its correlation with heterogeneity of tumor immune microenvironment. PeerJ 2024;12:e18579.
25. Hsieh RC-E, Krishnan S, Wu R-C et al. ATR-mediated CD47 and PD-L1 up-regulation restricts radiotherapy-induced immune priming and abscopal responses in colorectal cancer. Sci Immunol 2022;7:eabl9330.
26. Roelands J, Van der Ploeg M, Ijsselsteijn ME, Dang H, Boonstra JJ, Hardwick JC, et al. Transcriptomic and immunophenotypic profiling reveals molecular and immunological hallmarks of colorectal cancer tumourigenesis. Gut 2023;72:1326-39.
27. Fujiwara-Tani R, Sasaki T, Ohmori H, Luo Y, Goto K, Nishiguchi Y et al. Concurrent expression of CD47 and CD44 in colorectal cancer promotes malignancy. Pathobiol 2019;86:182-9.
28. Sugimura-Nagata A, Koshino A, Inoue S et al. Expression and prognostic significance of CD47–SIRPA macrophage checkpoint molecules in colorectal cancer. Int J Molec Sci 2021;22:2690.