The expression and clinical significance of apolipoprotein C1 in cervix cancer

Cervical cancer (CC) is the fourth largest cancer affecting the global survival of women. Apolipoprotein C1 (APOC1) has been implicated in the pathogenesis and progression of various malignancies. Here, we investigated the expression and clinical significance of APOC1 in patients with CC. Gene expression data and the corresponding clinical features of CC were downloaded from the Gene Expression Omnibus (GEO) database. The expression levels of APOC1 were evaluated by the R software package. An enzyme-linked immunosorbent assay (ELISA) was used to detect the serum levels of APOC1 expression in 120 CC patients and 60 healthy controls. The diagnostic value of serum APOC1 level for CC was then evaluated by receiver operating characteristic curve analysis. The expression levels of APOC1 in CC tissue were significantly higher than that in adjacent tissues (p < 0.001). ELISA further confirmed that serum levels of APOC1 were significantly higher in CC patients than im normal controls (p < 0.001). With an area under the curve (AUC) of 0.826 (95% confidence interval: 0.766–0.888; p < 0.05), serum APOC1 can serve as a reliable molecular biomarker for differentiating CC patients from healthy controls. Moreover, we found that elevated serum APOC1 levels were significantly associated with poor clinical stage (p = 0.025) and positive lymph node metastasis (p = 0.002). In addition, serum APOC1 level was positively correlated with clinical stage (p < 0.01) and lymph node metastasis (p < 0.05) in CC patients. Thus, our results indicated that serum APOC1 was significantly higher in tissues and serum from CC patients and represents a potential novel biomarker for the diagnosis of CC.

Cervical cancer; Apolipoprotein C1; Diagnostic markers

[1] Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA: A Cancer Journal for Clinicians. 2023; 73: 17–48.

[2] Singh D, Vignat J, Lorenzoni V, Eslahi M, Ginsburg O, Lauby-Secretan B, et al. Global estimates of incidence and mortality of cervical cancer in 2020: a baseline analysis of the WHO Global Cervical Cancer Elimination Initiative. The Lancet Global Health. 2023; 11: e197–e206.

[3] Gavinski K, DiNardo D. Cervical cancer screening. Medical Clinics of North America. 2023; 107: 259–269.

[4] Guillaume D, Waheed D, Schlieff M, Muralidharan K, Vorsters A, Limaye R. Key decision-making factors for human papillomavirus (HPV) vaccine program introduction in low-and-middle-income-countries: global and national stakeholder perspectives. Human Vaccines & Immunotherapeutics. 2022; 18: 2150454.

[5] Gennigens C, Jerusalem G, Lapaille L, De Cuypere M, Streel S, Kridelka F, et al. Recurrent or primary metastatic cervical cancer: current and future treatments. ESMO Open. 2022; 7: 100579.

[6] Miller KM, Friedman CF. Bifunctional blockade: a novel immunotherapy approach for cervical cancer. Clinical Cancer Research. 2022; 28: 5238–5240.

[7] Fuior EV, Gafencu AV. Apolipoprotein C1: its pleiotropic effects in lipid metabolism and beyond. International Journal of Molecular Sciences. 2019; 20: 5939.

[8] Björkegren J, Karpe F, Milne RW, Hamsten A. Differences in apolipoprotein and lipid composition between human chylomicron remnants and very low density lipoproteins isolated from fasting and postprandial plasma. Journal of Lipid Research. 1998; 39: 1412–1420.

[9] Albers J. Effect of human plasma apolipoproteins on the activity of purified lecithin:cholesterol acyltransferase. Scandinavian Journal of Clinical and Laboratory Investigation. 1978; 38: 48–52.

[10] Armitage J, Holmes MV, Preiss D. Cholesteryl ester transfer protein inhibition for preventing cardiovascular events. Journal of the American College of Cardiology. 2019; 73: 477–487.

[11] Lauer SJ, Walker D, Elshourbagy NA, Reardon CA, Levy-Wilson B, Taylor JM. Two copies of the human apolipoprotein C-I gene are linked closely to the apolipoprotein E gene. Journal of Biological Chemistry. 1988; 263: 7277–7286.

[12] Hao X, Zheng Z, Liu H, Zhang Y, Kang J, Kong X, 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 Biology. 2022; 56: 102463.

[13] Guo Q, Liu XL, Jiang N, Zhang WJ, Guo SW, Yang H, et al. Decreased APOC1 expression inhibited cancer progression and was associated with better prognosis and immune microenvironment in esophageal cancer. American Journal of Cancer Research. 2022; 12: 4904–4929.

[14] Croyal M, Wargny M, Chemello K, Chevalier C, Blanchard V, Bigot-Corbel E, et al. Plasma apolipoprotein concentrations and incident diabetes in subjects with prediabetes. Cardiovascular Diabetology. 2022; 21: 21.

[15] Ko HL, Wang YS, Fong WL, Chi MS, Chi KH, Kao SJ. Apolipoprotein C1 (APOC1) as a novel diagnostic and prognostic biomarker for lung cancer: a marker phase I trial. Thoracic Cancer. 2014; 5: 500–508.

[16] Su W, Sun L, Yang S, Zhao H, Zeng T, Wu W, et al. Apolipoprotein C1 promotes prostate cancer cell proliferation in vitro. Journal of Biochemical and Molecular Toxicology. 2018; 32: e22158.

[17] Peng Y, Dong S, Yang Z, Song Y, Ding J, Hou D, et al. Identification of docetaxel‐related biomarkers for prostate cancer. Andrologia. 2021; 53: e14079.

[18] Liang R, Zhang G, Xu W, Liu W, Tang Y. ApoC1 promotes glioma metastasis by enhancing epithelial-mesenchymal transition and activating the STAT3 pathway. Neurological Research. 2023; 45: 268–275.

[19] Yan Y, Zhou Y, Wang K, Qiao Y, Zhao L, Chen M. Apolipoprotein C1 (APOC1), a candidate diagnostic serum biomarker for breast cancer identified by serum proteomics study. Critical Reviews in Eukaryotic Gene Expression. 2022; 32: 1–9.

[20] Zhang H, Wang Y, Liu C, Li W, Zhou F, Wang X, et al. The apolipoprotein C1 is involved in breast cancer progression via EMT and MAPK/JNK pathway. Pathology—Research and Practice. 2022; 229: 153746.

[21] Uhlen M, Zhang C, Lee S, Sjöstedt E, Fagerberg L, Bidkhori G, et al. A pathology atlas of the human cancer transcriptome. Science. 2017; 357: eaan2507.

[22] Castanon A, Kamineni A, Elfström KM, Lim AWW, Sasieni P. Exposure definition in case—control studies of cervical cancer screening: a systematic literature review. Cancer Epidemiology, Biomarkers & Prevention. 2021; 30: 2154–2166.

[23] Bus P, Pierneef L, Bor R, Wolterbeek R, van Es LA, Rensen PC, et al. Apolipoprotein C-I plays a role in the pathogenesis of glomerulosclerosis. The Journal of Pathology. 2017; 241: 589–599.

[24] Yi J, Ren L, Wu J, Li W, Zheng X, Du G, et al. Apolipoprotein C1 (APOC1) as a novel diagnostic and prognostic biomarker for gastric cancer. Annals of Translational Medicine. 2019; 7: 380–380.

[25] Gonçalves A, Esterni B, Bertucci F, Sauvan R, Chabannon C, Cubizolles M, et al. Postoperative serum proteomic profiles may predict metastatic relapse in high-risk primary breast cancer patients receiving adjuvant chemotherapy. Oncogene. 2006; 25: 981–989.

[26] Takano S, Yoshitomi H, Togawa A, Sogawa K, Shida T, Kimura F, et al. Apolipoprotein C-1 maintains cell survival by preventing from apoptosis in pancreatic cancer cells. Oncogene. 2008; 27: 2810–2822.

[27] Jiang H, Tang J, Xue D, Chen Y, Wu T, Zhuang Q, et al. Apolipoprotein C1 stimulates the malignant process of renal cell carcinoma via the Wnt3a signaling. Cancer Cell International. 2021; 21: 41.

[28] Shi X, Wang J, Dai S, Qin L, Zhou J, Chen Y. Apolipoprotein C1 (APOC1): a novel diagnostic and prognostic biomarker for cervical cancer. OncoTargets and Therapy. 2020; 13: 12881–12891.

[29] Sato N, Fukushima N, Chang R, Matsubayashi H, Goggins M. Differential and epigenetic gene expression profiling identifies frequent disruption of the RELN pathway in pancreatic cancers. Gastroenterology. 2006; 130: 548–565.

[30] Zheng X, Chen W, Yi J, Li W, Liu J, Fu W, et al. Apolipoprotein C1 promotes glioblastoma tumorigenesis by reducing KEAP1/NRF2 and CBS-regulated ferroptosis. Acta Pharmacologica Sinica. 2022; 43: 2977–2992.