Expression and prognostic factors analysis of CYFRA21-1, CEA, and Ki67 in non-small cell lung cancer_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

PAN Jianyun ¹ , HUANG Yien ² , HONG Shujun ² , FANG Shaohan ² , LIU Jingwei ¹ , CHEN Weiqiang ² , PAN Gaojian ¹ ,  JIANG Jie ² ,  GENG Guojun ^1,2,3

1. Department of Thoracic Surgery, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361003, Fujian, P. R. China;
2. Department of Thoracic Surgery, The First Affiliated Hospital of Xiamen University, Xiamen, 361003, Fujian, P. R. China;
3. The Third Clinical Medical College, Fujian Medical University, Fuzhou, 350122, P. R. China;

Corresponding author：

JIANG Jie, Email: jiangjie06@126.com; GENG Guojun, Email: ggj622@126.com

Keywords：

Non-small cell lung cancer; tumor markers; Ki67; prognosis

DOI：

10.7507/1007-4848.202310010

Video：

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Objective To explore the value of preoperative detection of soluble fragments of cytokeratin-19 (CYFRA21-1), carcinoembryonic antigen (CEA), and postoperative detection of nuclear proliferation associated antigen Ki67 in prognostic evaluation of non-small cell lung cancer patients. Methods The clinicopathological data and follow-up results of patients with non-small cell lung cancer treated in the Department of Thoracic Surgery of the First Affiliated Hospital of Xiamen University in 2017 were collected. CYFRA21-1>3.39 ng/mL was defined as positive, and CEA>5 ng/mL was defined as positive. The receiver operating characteristic curve (ROC curve) of Ki67 expression level was drawn. The maximum area under the curve (AUC) was the cutoff value of Ki67 expression level, and the Ki67 expression level greater than its cutoff value was defined as positive. Cox regression analysis was used to determine the independent risk factors for poor prognosis in patients with non-small cell lung cancer. Results Finally 248 patients were collected, including 125 males and 123 females, with a median age of 61 years (ranging from 30 to 81 years) at the time of surgery. Univariate analysis showed that positive CYFRA21-1, high expression of Ki67, positive CEA, age≥60 years at operation, distant metastasis, lymph node metastasis, maximum tumor diameter>3 cm, and TNM stage Ⅲ were associated with poor prognosis in patients with non-small cell lung cancer. When combined detection of preoperative tumor markers and postoperative Ki67, the prognosis of all negative patients was the best, and that of all positive patients was the worst. Cox regression analysis showed that positive CEA+positive CYFRA21-1+high expression of Ki67 was an independent risk factor for poor prognosis in patients with non-small cell lung cancer (P<0.05). Conclusion The combined detection of preoperative serum CYFRA21-1, CEA, and postoperative Ki67 has important value in evaluating the prognosis of non-small cell lung cancer patients.

Citation： PAN Jianyun, HUANG Yien, HONG Shujun, FANG Shaohan, LIU Jingwei, CHEN Weiqiang, PAN Gaojian, JIANG Jie, GENG Guojun. Expression and prognostic factors analysis of CYFRA21-1, CEA, and Ki67 in non-small cell lung cancer. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2024, 31(5): 682-688. doi: 10.7507/1007-4848.202310010 Copy

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10.	Booth DG, Takagi M, Sanchez-Pulido L, et al. Ki-67 is a PP1-interacting protein that organises the mitotic chromosome periphery. Elife, 2014, 3: e01641.
11.	Li T, Xie Q, Fang YY, et al. Prognostic value of CYFRA 21-1 and Ki67 in advanced NSCLC patients with wild-type EGFR. BMC Cancer, 2023, 23(1): 295.
12.	Ciancio N, Galasso MG, Campisi R, et al. Prognostic value of p53 and Ki67 expression in fiberoptic bronchial biopsies of patients with non small cell lung cancer. Multidiscip Respir Med, 2012, 7(1): 29.
13.	Yang Q, Zhang P, Wu R, et al. Identifying the best marker combination in CEA, CA125, CY211, NSE, and SCC for lung cancer screening by combining ROC curve and logistic regression Analyses: Is it feasible? Dis Markers, 2018, 2018: 2082840.
14.	Onuki Y, Matsubara H, Koizumi R, et al. Prognostic evaluation of preoperative serum tumor marker-negative cases in non-small cell lung cancer: A retrospective study. Cancer Rep (Hoboken), 2023, 6(2): e1696.
15.	Li J, Chen Y, Wang X, et al. The value of combined detection of CEA, CYFRA21-1, SCC-Ag, and pro-GRP in the differential diagnosis of lung cancer. Transl Cancer Res, 2021, 10(4): 1900-1906.
16.	Wang B, He YJ, Tian YX, et al. Clinical utility of haptoglobin in combination with CEA, NSE and CYFRA21-1 for diagnosis of lung cancer. Asian Pac J Cancer Prev, 2014, 15(22): 9611-9614.
17.	Qin WW, Wang P, Ding C, et al. Difference of serum tumor markers in different clinical stages of elderly patients with non-small cell lung cancer and evaluation of diagnostic value. J Med Biochem, 2023, 42(4): 607-615.
18.	Arrieta O, Varela-Santoyo E, Cardona AF, et al. Association of carcinoembryonic antigen reduction with progression-free and overall survival improvement in advanced non-small-cell lung cancer. Clin Lung Cancer, 2021, 22(6): 510-522.

1. Miller KD, Nogueira L, Devasia T, et al. Cancer treatment and survivorship statistics, 2022. CA Cancer J Clin, 2022, 72(5): 409-436.
2. 陈万青, 郑荣寿, 张思维, 等. 2013年中国恶性肿瘤发病和死亡分析. 中国肿瘤, 2017, 26(1): 1-7.
3. 王鑫, 支修益. 国际肺癌研究协会(IASLC)第八版肺癌TNM分期解读. 中华胸部外科电子杂志, 2016, 3(2): 70-76.
4. Grunnet M, Sorensen JB. Carcinoembryonic antigen (CEA) as tumor marker in lung cancer. Lung Cancer, 2012, 76(2): 138-143.
5. Fu L, Wang R, Yin L, et al. CYFRA21-1 tests in the diagnosis of non-small cell lung cancer: A meta-analysis. Int J Biol Markers, 2019, 34(3): 251-261.
6. 周转, 陶旭秀, 周沛军, 等. PD-L1联合Ki67对非小细胞肺癌不同基因突变情况下分期、预后的影响. 中国免疫学杂志, 2023, 39(4): 804-808.
7. Hao C, Zhang G, Zhang L. Serum CEA levels in 49 different types of cancer and noncancer diseases. Prog Mol Biol Transl Sci, 2019, 162: 213-227.
8. Jiao Z, Cao S, Li J, et al. Clinical associations of preoperative and postoperative serum CEA and lung cancer outcome. Front Mol Biosci, 2021, 8: 686313.
9. Matsuoka K, Sumitomo S, Nakashima N, et al. Prognostic value of carcinoembryonic antigen and CYFRA21-1 in patients with pathological stageⅠnon-small cell lung cancer. Eur J Cardiothorac Surg, 2007, 32(3): 435-439.
10. Booth DG, Takagi M, Sanchez-Pulido L, et al. Ki-67 is a PP1-interacting protein that organises the mitotic chromosome periphery. Elife, 2014, 3: e01641.
11. Li T, Xie Q, Fang YY, et al. Prognostic value of CYFRA 21-1 and Ki67 in advanced NSCLC patients with wild-type EGFR. BMC Cancer, 2023, 23(1): 295.
12. Ciancio N, Galasso MG, Campisi R, et al. Prognostic value of p53 and Ki67 expression in fiberoptic bronchial biopsies of patients with non small cell lung cancer. Multidiscip Respir Med, 2012, 7(1): 29.
13. Yang Q, Zhang P, Wu R, et al. Identifying the best marker combination in CEA, CA125, CY211, NSE, and SCC for lung cancer screening by combining ROC curve and logistic regression Analyses: Is it feasible? Dis Markers, 2018, 2018: 2082840.
14. Onuki Y, Matsubara H, Koizumi R, et al. Prognostic evaluation of preoperative serum tumor marker-negative cases in non-small cell lung cancer: A retrospective study. Cancer Rep (Hoboken), 2023, 6(2): e1696.
15. Li J, Chen Y, Wang X, et al. The value of combined detection of CEA, CYFRA21-1, SCC-Ag, and pro-GRP in the differential diagnosis of lung cancer. Transl Cancer Res, 2021, 10(4): 1900-1906.
16. Wang B, He YJ, Tian YX, et al. Clinical utility of haptoglobin in combination with CEA, NSE and CYFRA21-1 for diagnosis of lung cancer. Asian Pac J Cancer Prev, 2014, 15(22): 9611-9614.
17. Qin WW, Wang P, Ding C, et al. Difference of serum tumor markers in different clinical stages of elderly patients with non-small cell lung cancer and evaluation of diagnostic value. J Med Biochem, 2023, 42(4): 607-615.
18. Arrieta O, Varela-Santoyo E, Cardona AF, et al. Association of carcinoembryonic antigen reduction with progression-free and overall survival improvement in advanced non-small-cell lung cancer. Clin Lung Cancer, 2021, 22(6): 510-522.

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