Diagnosis of bone metastasis in patients with non-small cell lung cancer by combined detection of CEA, CYFRA21-1, and ALP

Haiying Ye; Qiaoli  Zhang

doi:10.2298/VSP250107057Y

Haiying Ye Xinchang Hospital of Traditional Chinese Medicine, Department of Laboratory Medicine, Shaoxing, Zhejiang, China
Qiaoli Zhang Xinchang Hospital of Traditional Chinese Medicine, Department of Laboratory Medicine, Shaoxing, Zhejiang, China

DOI: https://doi.org/10.2298/VSP250107057Y

Keywords: biomarkers, tumor;, bone neoplasms;, carcinoma, non-small-cell lung;, diagnosis;, neoplasm metastasis;, treatment outcome

Abstract

Background/Aim. Despite significant advances in the diagnosis and treatment of non-small cell lung cancer (NSCLC), the overall prognosis remains poor, especially when bone metastasis occurs with disease progression. The aim of this study was to examine the diagnostic value of combined detection of carcinoembryonic antigen (CEA), cytokeratin 19 fragment antigen 21-1 (CYFRA21-1), and alkaline phosphatase (ALP) for bone metastasis in NSCLC patients. Methods. In total, 148 patients with NSCLC were included in the study. They were selected from patients hospitalized for treatment between April 2020 and March 2022. Out of the total number of patients, 68 were assigned to the metastasis group and 80 to the non-metastasis group. Their blood samples were collected to measure CEA, CYFRA21-1, and ALP levels in the serum. Multivariate logistic regression analysis was conducted to determine the factors contributing to bone metastasis. Receiver operating characteristic (ROC) curves were plotted to analyze the diagnostic value. Results. Bone metastasis occurred in 68 (45.94%) patients. The baseline data exhibited no significant intergroup differences (p > 0.05). The metastasis group had significantly raised serum CEA, CYFRA21-1, and ALP levels compared to those of the non-metastasis group (p < 0.05). The increases in serum CEA [odds ratio (OR): 1.062, 95% confidence interval (CI): 1.031–1.094], CYFRA21-1 (OR: 1.155, 95% CI: 1.061–1.258), and ALP (OR: 1.027, 95% CI: 1.008–1.047) were risk factors for bone metastasis (OR > 1, p < 0.05). The areas under the ROC curves of CEA, CYFRA21-1, ALP, and their combination were all greater than 0.600, suggesting high diagnostic values. Conclusion. CEA, CYFRA21-1, and ALP levels in the serum can predict bone metastasis in NSCLC patients, and the predictive value of their combination is higher than that of any single indicator.

References

Chen P, Liu Y, Wen Y, Zhou C. Non-small cell lung cancer in China. Cancer Commun (Lond) 2022; 42(10): 937–70.

Bessa CM, Silva LMD, Zamboni MM, Costa GJ, Bergmann A, Thuler LCS, et al. Bone metastasis after stage IIIA non-small cell lung cancer: risks and prognosis. J Bras Pneumol 2022; 48(5): e20220211.

Lim CH, Ahn TR, Moon SH, Cho YS, Choi JY, Kim BT, et al. PET/CT features discriminate risk of metastasis among single-bone FDG lesions detected in newly diagnosed non-small-cell lung cancer patients. Eur Radiol 2019; 29(4): 1903–11.

Imura Y, Yamamoto S, Wakamatsu T, Tanaka T, Tamiya H, Sugimura K, et al. Clinical features and prognostic factors in patients with esophageal cancer with bone metastasis. Oncol Lett 2020; 19(1): 717–24.

Li C, Liu L, You R, Li Y, Pu H, Lei M, et al. Trajectory pat-terns and cumulative burden of CEA during follow-up with non-small cell lung cancer outcomes: A retrospective longitu-dinal cohort study. Br J Cancer 2024; 130(11): 1803–8.

Li Q, Sang S. Diagnostic Value and Clinical Significance of Combined Detection of Serum Markers CYFRA21-1, SCC Ag, NSE, CEA and ProGRP in Non-Small Cell Lung Carci-noma. Clin Lab 2020; 66(11): 2189.

Mohamed E, García Martínez DJ, Hosseini MS, Yoong SQ, Fletcher D, Hart S, et al. Identification of biomarkers for the early de-tection of non-small cell lung cancer: a systematic review and meta-analysis. Carcinogenesis 2024; 45(1–2): 1–22.

Chai X, Yinwang E, Wang Z, Wang Z, Xue Y, Li B, et al. Pre-dictive and Prognostic Biomarkers for Lung Cancer Bone Me-tastasis and Their Therapeutic Value. Front Oncol 2021; 11: 692788.

Yang T, Cheng J, Fu S, Sun T, Yang K, You J, et al. Pretreatment levels of serum alkaline phosphatase are associated with the prognosis of patients with non small cell lung cancer receiving immune checkpoint inhibitors. Oncol Lett 2023; 25(4): 154.

Dietel M, Bubendorf L, Dingemans AM, Dooms C, Elmberger G, García RC, et al. Diagnostic procedures for non-small-cell lung cancer (NSCLC): recommendations of the European Expert Group. Thorax 2016; 71(2): 177–84.

Alexander M, Kim SY, Cheng H. Update 2020: Management of Non-Small Cell Lung Cancer. Lung 2020; 198(6): 897–907.

Del Conte A, De Carlo E, Bertoli E, Stanzione B, Revelant A, Ber-tola M, et al. Bone Metastasis and Immune Checkpoint Inhibi-tors in Non-Small Cell Lung Cancer (NSCLC): Microenvi-ronment and Possible Clinical Implications. Int J Mol Sci 2022; 23(12): 6832.

Li Y, Xu C, Yu Q. Risk factor analysis of bone metastasis in patients with non-small cell lung cancer. Am J Transl Res 2022; 14(9): 6696–702.

Ikeda T, Kitajima K, Tsuchitani T, Takahashi Y, Hama Y, Kotura N. Effectiveness of quantitative bone SPECT/CT for bone metastasis diagnosis. Hell J Nucl Med 2022; 25(3): 253–9.

Göbel A, Dell'Endice S, Jaschke N, Pählig S, Shahid A, Hofbauer LC, et al. The Role of Inflammation in Breast and Prostate Cancer Metastasis to Bone. Int J Mol Sci 2021; 22(10): 5078.

Filella X, Rodríguez-Garcia M, Fernández-Galán E. Clinical use-fulness of circulating tumor markers. Clin Chem Lab Med 2022; 61(5): 895–905.

Uygur MM, Gümüş M. The utility of serum tumor markers CEA and CA 15-3 for breast cancer prognosis and their asso-ciation with clinicopathological parameters. Cancer Treat Res Commun 2021; 28: 100402.

Bes-Scartezini F, Saad Junior R. Prognostic assessment of tumor markers in lung carcinomas. Rev Assoc Med Bras (1992) 2022; 68(3): 313–7.

Nakao M, Kinoshita R, Kuriyama M, Kiyotoshi H, Sugihara M, Takeda N, et al. Serum CYFRA 21-1 Level as a Prognostic Marker for Extensive Disease Small Cell Lung Cancer. Anti-cancer Res 2024; 44(2): 845–51.

Xue F, Meng Y, Jiang J. Diagnostic Value of Dynamic En-hanced Magnetic Resonance Imaging Combined with Serum CA15-3, CYFRA21-1, and TFF1 for Breast Cancer. J Healthc Eng 2022; 2022: 7984591.

Zou Y, Liu Z, Li H, Hou L, Pang J, Liu X, et al. Evaluation of bone metabolism-associated biomarkers in Tibet, China. J Clin Lab Anal 2021; 35(12): e24068.

Shalata W, Yakobson A, Steckbeck R, Jama AA, Abu Saleh O, Agbarya A. Is Elevation of Alkaline Phosphatase a Predictive Factor of Response to Alectinib in NSCLC? Curr Oncol 2021; 29(1): 173–7.

Li L, Xu Y, Wang Y, Zhang Q, Wang Y, Xu C. The Diagnostic and Prognostic Value of the Combination of Tumor M2-Pyruvate Kinase, Carcinoembryonic Antigen, and Cytokeratin 19 Fragment in Non-Small Cell Lung Cancer. Technol Cancer Res Treat 2024; 23: 15330338241265983.