The Relationship Between APOC1 Expression And Prognostic Parameters And Survival In Colorectal Cancer
Yıl 2025,
Cilt: 4 Sayı: 3, 111 - 117, 25.12.2025
Esra Çeçen
,
Muhammet Çalık
,
Sena Özcan Yıldırım
Öz
Objective: Colorectal cancer (CRC) is the third most common type of cancer worldwide and the second leading cause of cancer-related deaths. Recent studies have illustraten that apolipoprotein C1 (APOC1) promotes carcinogenesis in certain human cancers. The objective of our study was to determine the association between APOC1 expression and prognostic factors, and survival.
Methods: H&E-stained and immunohistochemical(IHC) preparations from colon resection specimens of 90 patients, diagnosed between 2008 and 2018, were examined. APOC1 overexpression was evaluated using an IHC score based on nuclear staining intensity (0-3) and the percentage of positive tumor cells (0-4). Pearson's Chi-Square and Fisher’s exact test were employed to investigate the association between APOC1 expression and prognostic parameters statistically. Kaplan Meier’s and Cox regresion tests were employed to investigate the association between APOC1 expression and survival.
Results: The median age of the patients was 63.3 years (Min:34, Max:88). No statistically significant correlation was revealed between APOC1 staining index and gender, age, tumour localisation, histological grade, tumour infiltrating lymphocytes, lymphovascular invasion, perineural invasion, N stage, metastasis and TNM stage (p>0.05). Hıgh IHC expression of APOC1 was correlated with macroscopic tumour diameter and T stage (p<0.05). APOC1 overexpression in CRC tissues was associated with unfavorable prognosis. Univariate Cox regression analyses demonstrated that APOC1 was an independent risk factor for overall survival (OS).
Conclusion:APOC1 overexpression in CRC tissues was associated with poorer survival. APOC1 has been revealed to be an independent prognostic marker in CRC.
Etik Beyan
Ethics committee approval was obtained from Firat University Local Ethics Committee (14 September 2023, Session Number: 2023/12-45).
Destekleyen Kurum
Fırat University Scientific Research Projects Coordination Unit (FÜBAP),Elazig
Kaynakça
-
1. Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-249. doi:10.3322/caac.21660
-
2. Weiser MR. AJCC 8th Edition: Colorectal Cancer. Ann Surg Oncol. 2018;25(6):1454-1455. doi:10.1245/s10434-018-6462-1
-
3. College of American Pathologists C. Protocol for the Examination of Specimens from Patients with Primary Carcinoma of the Colon and Rectum.; 2017. www.cap.org/cancerprotocols.
-
4. Puppa G, Sonzogni A, Colombari R, Pelosi G. TNM staging system of colorectal carcinoma: a critical appraisal of challenging issues. Arch Pathol Lab Med. 2010;134(6):837-852. doi:10.5858/134.6.837
-
5. Mármol I, Sánchez-de-Diego C, Pradilla Dieste A, Cerrada E, Rodriguez Yoldi MJ. Colorectal Carcinoma: A General Overview and Future Perspectives in Colorectal Cancer. Int J Mol Sci. 2017;18(1):197. doi:10.3390/ijms18010197
-
6. Yu K, Ding L, An X, et al. APOC1 exacerbates renal fibrosis through the activation of the NF-κB signaling pathway in IgAN. Front Pharmacol. 2023;14:1181435. doi:10.3389/fphar.2023.1181435
-
7. Ren H, Chen Z, Yang L, et al. Apolipoprotein C1 (APOC1) promotes tumor progression via MAPK signaling pathways in colorectal cancer. Cancer Manag Res. 2019;11:4917-4930. doi:10.2147/CMAR.S192529
-
8. Ren L, Yi J, Yang Y, et al. Systematic pan-cancer analysis identifies APOC1 as an immunological biomarker which regulates macrophage polarization and promotes tumor metastasis. Pharmacol Res. 2022;183:106376. doi:10.1016/j.phrs.2022.106376
-
9. Lee GH, Malietzis G, Askari A, Bernardo D, Al-Hassi HO, Clark SK. Is right-sided colon cancer different to left-sided colorectal cancer? - a systematic review. Eur J Surg Oncol. 2015;41(3):300-308. doi:10.1016/j.ejso.2014.11.001
-
10. Rosai J. Rosai and Ackerman’s Surgical Pathology. Vol 1. 10th ed. (Houston M, ed.). Elsevier; 2011.
-
11. Besiroglu M, Demir T. Which is the worse prognostic factor in patients with stage III colorectal cancer: tumor 4 or node 2?. J BUON. 2020;25(4):1847-1853.
-
12. Li J, Hubisz MJ, Earlie EM, et al. Non-cell-autonomous cancer progression from chromosomal instability. Nature. 2023;620(7976):1080-1088. doi:10.1038/s41586-023-06464-z
-
13. Yang Y, Yang Z, Lyu Z, et al. Pathological-Features-Modified TNM Staging System Improves Prognostic Accuracy for Rectal Cancer. Dis Colon Rectum. 2024;67(5):645-654. doi:10.1097/DCR.0000000000003034
-
14. Ye L, Zhang T, Kang Z, et al. Tumor-Infiltrating Immune Cells Act as a Marker for Prognosis in Colorectal Cancer. Front Immunol. 2019;10:2368. doi:10.3389/fimmu.2019.02368
-
15. Xu W, Zhu Y, Shen W, et al. Combination of CDX2 expression and T stage improves prognostic prediction of colorectal cancer. J Int Med Res. 2019;47(5):1829-1842. doi:10.1177/0300060518819620
-
16. Johdi NA, Sukor NF. Colorectal Cancer Immunotherapy: Options and Strategies. Front Immunol. 2020;11:1624. doi:10.3389/fimmu.2020.01624
-
17. Ganesh K. Optimizing immunotherapy for colorectal cancer. Nat Rev Gastroenterol Hepatol. 2022;19(2):93-94. doi:10.1038/s41575-021-00569-4
-
18. Zhao W, Jin L, Chen P, Li D, Gao W, Dong G. Colorectal cancer immunotherapy-Recent progress and future directions. Cancer Lett. 2022;545:215816. doi:10.1016/j.canlet.2022.215816
-
19. Takano S, Yoshitomi H, Togawa A, et al. Apolipoprotein C-1 maintains cell survival by preventing from apoptosis in pancreatic cancer cells. Oncogene. 2008;27(20):2810-2822. doi:10.1038/sj.onc.1210951
-
20. Yang S, Du J, Wang W, Zhou D, Xi X. APOC1 is a prognostic biomarker associated with M2 macrophages in ovarian cancer. BMC Cancer. 2024;24(1):364. doi:10.1186/s12885-024-12105-z
-
21. Zheng XJ, Chen WL, Yi J, et al. Apolipoprotein C1 promotes glioblastoma tumorigenesis by reducing KEAP1/NRF2 and CBS-regulated ferroptosis. Acta Pharmacol Sin. 2022;43(11):2977-2992. doi:10.1038/s41401-022-00917-3
-
22. Cui Y, Miao C, Hou C, Wang Z, Liu B. Apolipoprotein C1 (APOC1): A Novel Diagnostic and Prognostic Biomarker for Clear Cell Renal Cell Carcinoma. Front Oncol. 2020;10:1436. doi:10.3389/fonc.2020.01436
-
23. Gu Q, Zhan T, Guan X, et al. Apolipoprotein C1 promotes tumor progression in gastric cancer. Oncol Res. 2023;31(3):287-297. doi:10.32604/or.2023.028124
-
24. Hao X, Zheng Z, Liu H, et al. Inhibition of APOC1 promotes the transformation of M2 into M1 macrophages via the ferroptosis pathway and enhances anti-PD1 immunotherapy in hepatocellular carcinoma based on single-cell RNA sequencing. Redox Biol. 2022;56:102463. doi:10.1016/j.redox.2022.102463
-
25. Mei L, Long J, Wu S, Mei M, Mei D, Qiu H. APOC1 reduced anti-PD-1 immunotherapy of nonsmall cell lung cancer via the transformation of M2 into M1 macrophages by ferroptosis by NRF2/HO-1. Anticancer Drugs. 2024;35(4):333-343. doi:10.1097/CAD.0000000000001573
Kolorektal Kanserlerde APOC1 Ekspresyonunun Prognostik Parametreler Ve Sağkalım İle İlişkisinin Araştırılması
Yıl 2025,
Cilt: 4 Sayı: 3, 111 - 117, 25.12.2025
Esra Çeçen
,
Muhammet Çalık
,
Sena Özcan Yıldırım
Öz
Amaç : : Kolorektal kanserler, dünya genelinde en sık görülen üçüncü kanser türü olup kansere bağlı ölümlerde ise ikinci sırada yer almaktadırlar. Son dönemlerde Apolipoprotein C1'in (APOC1) bazı insan kanserlerinde karsinogenezi desteklediğini gösteren çalışmalar yapılmıştır. Çalışmamızda KRK’lerde APOC1 ekspresyonunun prognostik faktörler ve sağkalım ile ilişkisini belirlemeyi amaçladık.
Yöntemler : : 2008 ile 2018 yılları arasında tanı konulan 90 hastanın kolon rezeksiyon örneklerinden alınan H&E boyalı ve immünohistokimyasal (IHK) preparatlar incelendi. APOC1 aşırı ekspresyonu, nükleer boyama yoğunluğu (0-3) ve pozitif tümör hücrelerinin yüzdesi (1-3) temel alınarak IHK skoru kullanılarak değerlendirildi. APOC1 ekspresyonu ile prognostik parametreler arasındaki ilişkiyi istatistiksel olarak analiz etmek için Pearson Ki-Kare ve Fisher’s exact testi kullanıldı. APOC1 ekspresyonu ile sağkalım arasındaki ilişkiyi analiz etmek için Kaplan Meier ve Cox regresyon testleri kullanıldı.
Bulgular Çalışmada hastaların median yaşı 63,3’tür. KRK’li dokularda yüksek APOC1 ekspresyonu ile olguların makroskopik tümör çapı ve T evresi arasında anlamlı ilişki tespit edildi (p<0.05). Ancak cinsiyet, yaş, tümör lokalizasyonu, histolojik grade, tümörü infiltre eden lenfositler, lenfovasküler invazyon, risk faktörü olduğunu gösterdi.duğunu gösterdi.
Sonuç : APOC1 aşırı ekspresyonunun daha kötü sağkalım ile ilişkilendirilmiştir. APOC1’in KRK’lerde bağımsız bir prognostik belirteç olarak kullanılabileceği tespit edilmiştir.
Etik Beyan
Etik kurul onayı Fırat Üniversitesi Girı̇şı̇msel Olmayan Araştırmalar Etik Kurulu’ndan (Tarih: 14.09.2023, Sayı: 2023/12-45) alınmıştır.
Destekleyen Kurum
Fırat Üniversitesi Bilimsel Araştırma Projeleri Koordinasyon Birimi(FUBAP)
Kaynakça
-
1. Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-249. doi:10.3322/caac.21660
-
2. Weiser MR. AJCC 8th Edition: Colorectal Cancer. Ann Surg Oncol. 2018;25(6):1454-1455. doi:10.1245/s10434-018-6462-1
-
3. College of American Pathologists C. Protocol for the Examination of Specimens from Patients with Primary Carcinoma of the Colon and Rectum.; 2017. www.cap.org/cancerprotocols.
-
4. Puppa G, Sonzogni A, Colombari R, Pelosi G. TNM staging system of colorectal carcinoma: a critical appraisal of challenging issues. Arch Pathol Lab Med. 2010;134(6):837-852. doi:10.5858/134.6.837
-
5. Mármol I, Sánchez-de-Diego C, Pradilla Dieste A, Cerrada E, Rodriguez Yoldi MJ. Colorectal Carcinoma: A General Overview and Future Perspectives in Colorectal Cancer. Int J Mol Sci. 2017;18(1):197. doi:10.3390/ijms18010197
-
6. Yu K, Ding L, An X, et al. APOC1 exacerbates renal fibrosis through the activation of the NF-κB signaling pathway in IgAN. Front Pharmacol. 2023;14:1181435. doi:10.3389/fphar.2023.1181435
-
7. Ren H, Chen Z, Yang L, et al. Apolipoprotein C1 (APOC1) promotes tumor progression via MAPK signaling pathways in colorectal cancer. Cancer Manag Res. 2019;11:4917-4930. doi:10.2147/CMAR.S192529
-
8. Ren L, Yi J, Yang Y, et al. Systematic pan-cancer analysis identifies APOC1 as an immunological biomarker which regulates macrophage polarization and promotes tumor metastasis. Pharmacol Res. 2022;183:106376. doi:10.1016/j.phrs.2022.106376
-
9. Lee GH, Malietzis G, Askari A, Bernardo D, Al-Hassi HO, Clark SK. Is right-sided colon cancer different to left-sided colorectal cancer? - a systematic review. Eur J Surg Oncol. 2015;41(3):300-308. doi:10.1016/j.ejso.2014.11.001
-
10. Rosai J. Rosai and Ackerman’s Surgical Pathology. Vol 1. 10th ed. (Houston M, ed.). Elsevier; 2011.
-
11. Besiroglu M, Demir T. Which is the worse prognostic factor in patients with stage III colorectal cancer: tumor 4 or node 2?. J BUON. 2020;25(4):1847-1853.
-
12. Li J, Hubisz MJ, Earlie EM, et al. Non-cell-autonomous cancer progression from chromosomal instability. Nature. 2023;620(7976):1080-1088. doi:10.1038/s41586-023-06464-z
-
13. Yang Y, Yang Z, Lyu Z, et al. Pathological-Features-Modified TNM Staging System Improves Prognostic Accuracy for Rectal Cancer. Dis Colon Rectum. 2024;67(5):645-654. doi:10.1097/DCR.0000000000003034
-
14. Ye L, Zhang T, Kang Z, et al. Tumor-Infiltrating Immune Cells Act as a Marker for Prognosis in Colorectal Cancer. Front Immunol. 2019;10:2368. doi:10.3389/fimmu.2019.02368
-
15. Xu W, Zhu Y, Shen W, et al. Combination of CDX2 expression and T stage improves prognostic prediction of colorectal cancer. J Int Med Res. 2019;47(5):1829-1842. doi:10.1177/0300060518819620
-
16. Johdi NA, Sukor NF. Colorectal Cancer Immunotherapy: Options and Strategies. Front Immunol. 2020;11:1624. doi:10.3389/fimmu.2020.01624
-
17. Ganesh K. Optimizing immunotherapy for colorectal cancer. Nat Rev Gastroenterol Hepatol. 2022;19(2):93-94. doi:10.1038/s41575-021-00569-4
-
18. Zhao W, Jin L, Chen P, Li D, Gao W, Dong G. Colorectal cancer immunotherapy-Recent progress and future directions. Cancer Lett. 2022;545:215816. doi:10.1016/j.canlet.2022.215816
-
19. Takano S, Yoshitomi H, Togawa A, et al. Apolipoprotein C-1 maintains cell survival by preventing from apoptosis in pancreatic cancer cells. Oncogene. 2008;27(20):2810-2822. doi:10.1038/sj.onc.1210951
-
20. Yang S, Du J, Wang W, Zhou D, Xi X. APOC1 is a prognostic biomarker associated with M2 macrophages in ovarian cancer. BMC Cancer. 2024;24(1):364. doi:10.1186/s12885-024-12105-z
-
21. Zheng XJ, Chen WL, Yi J, et al. Apolipoprotein C1 promotes glioblastoma tumorigenesis by reducing KEAP1/NRF2 and CBS-regulated ferroptosis. Acta Pharmacol Sin. 2022;43(11):2977-2992. doi:10.1038/s41401-022-00917-3
-
22. Cui Y, Miao C, Hou C, Wang Z, Liu B. Apolipoprotein C1 (APOC1): A Novel Diagnostic and Prognostic Biomarker for Clear Cell Renal Cell Carcinoma. Front Oncol. 2020;10:1436. doi:10.3389/fonc.2020.01436
-
23. Gu Q, Zhan T, Guan X, et al. Apolipoprotein C1 promotes tumor progression in gastric cancer. Oncol Res. 2023;31(3):287-297. doi:10.32604/or.2023.028124
-
24. Hao X, Zheng Z, Liu H, et al. Inhibition of APOC1 promotes the transformation of M2 into M1 macrophages via the ferroptosis pathway and enhances anti-PD1 immunotherapy in hepatocellular carcinoma based on single-cell RNA sequencing. Redox Biol. 2022;56:102463. doi:10.1016/j.redox.2022.102463
-
25. Mei L, Long J, Wu S, Mei M, Mei D, Qiu H. APOC1 reduced anti-PD-1 immunotherapy of nonsmall cell lung cancer via the transformation of M2 into M1 macrophages by ferroptosis by NRF2/HO-1. Anticancer Drugs. 2024;35(4):333-343. doi:10.1097/CAD.0000000000001573