Combination of serum ACSL4 levels and low-dose 256-slice spiral CT exhibits the potential in the early screening of lung cancer

Background: The prognosis of lung cancer is related to the stage of the disease at the time of detection, and early diagnosis can prolong survival time. In this prospective observational cohort research, we aimed to analyze the diagnostic performance of the combined application of ACSL4 and low-dose 256-slice spiral computed tomography (CT) to lung cancer. Methods: This prospective observational cohort research enrolled a total of 512 patients with pulmonary nodules (PN) who were found with PN by CT. All patients were divided into 2 groups through biopsy operation, including 449 patients with benign PN and 63 patients with malignant PN. Both groups were scanned with a Philips Brilliance 256iCT machine. Imaging features of PN were recorded. All images of the nodules were used for data measurement and image analysis by the Lung Nodule Assessment analysis software. The serum ACSL4, carcinoembryonic antigen (CEA), cytokeratin 19 fragment 21-1 (CYFRA21-1), neuron-specific enolase, carbohydrate antigen 199 (CA199) and carbohydrate antigen 125 (CA125) levels were measured by enzyme-linked immunosorbent assay method. The demographic data and clinical data, including age, sex, body mass index, smoke condition, TNM stage, lymph node metastasis and distant metastasis were collected. All the patients were followed for 5 years. Statistical analysis was conducted using SPSS software with P < .05 as statistically different. Results: The diameter of nodules, the proportion of burr signs and smoking status, and the serum levels of CEA, CYFRA21-1, CA199, CA125 were significantly higher in malignant nodules group compared with the benign nodules group. Serum ACSL4 levels of malignant nodules group (19.33 ± 6.92 ng/mL) were remarkably lower than the benign nodules group (25.34 ± 3.78 ng/mL). ACSL4 was negatively correlated with CEA, CYFRA21-1, CA199, and CA125. ACSL4 was associated with the clinical outcomes in malignant PN patients and lower ACSL4 predicted poor clinic outcomes and prognosis. In addition, ACSL4 combined with low-dose 256-slice spiral CT had satisfactory diagnostic value for lung cancer. Conclusion: In summary, our results showed that combination application of ACSL4 and low-dose 256-slice spiral CT might be a potential method for the early screening of lung cancer.

[1]  J. Zhang,et al.  Predictive and prognostic impact of ferroptosis-related genes ACSL4 and GPX4 on breast cancer treated with neoadjuvant chemotherapy , 2021, EBioMedicine.

[2]  Enqing Dong,et al.  Fusion of 3D lung CT and serum biomarkers for diagnosis of multiple pathological types on pulmonary nodules , 2021, Comput. Methods Programs Biomed..

[3]  M. Cabana,et al.  Screening for Lung Cancer: US Preventive Services Task Force Recommendation Statement. , 2021, JAMA.

[4]  A. Jemal,et al.  Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries , 2021, CA: a cancer journal for clinicians.

[5]  Zhang Shuang,et al.  Oleanolic acid inhibits cervical cancer Hela cell proliferation through modulation of the ACSL4 ferroptosis signaling pathway. , 2021, Biochemical and biophysical research communications.

[6]  S. Datta,et al.  Unraveling city-specific signature and identifying sample origin locations for the data from CAMDA MetaSUB challenge , 2020, Biology Direct.

[7]  Y. Shao,et al.  The Combination of CA125 and NSE Is Useful for Predicting Liver Metastasis of Lung Cancer , 2020, Disease markers.

[8]  T. Ochiya,et al.  A miRNA-based diagnostic model predicts resectable lung cancer in humans with high accuracy , 2020, Communications Biology.

[9]  C. D. Dela Cruz,et al.  Lung Cancer 2020: Epidemiology, Etiology, and Prevention. , 2020, Clinics in chest medicine.

[10]  G. Konstantinidou,et al.  Targeting Long Chain Acyl-CoA Synthetases for Cancer Therapy , 2019, International journal of molecular sciences.

[11]  C. Powell,et al.  Global Epidemiology of Lung Cancer , 2019, Annals of global health.

[12]  J. Javid,et al.  Clinical Significance of Circulatory miRNA-21 as an Efficient Non-Invasive Biomarker for the Screening of Lung Cancer Patients , 2018, Asian Pacific journal of cancer prevention : APJCP.

[13]  M. Gharabaghi Diagnostic investigation of BIRC6 and SIRT1 protein expression level as potential prognostic biomarkers in patients with non‐small cell lung cancer , 2018, The clinical respiratory journal.

[14]  A. Jemal,et al.  Cancer statistics, 2018 , 2018, CA: a cancer journal for clinicians.

[15]  Shuzhen Wei,et al.  hsa_circ_0013958: a circular RNA and potential novel biomarker for lung adenocarcinoma , 2017, The FEBS journal.

[16]  Barbara Sitek,et al.  Identification of the Consistently Altered Metabolic Targets in Human Hepatocellular Carcinoma , 2017, Cellular and molecular gastroenterology and hepatology.

[17]  Lihua Cao,et al.  Combining serum miRNAs, CEA, and CYFRA21-1 with imaging and clinical features to distinguish benign and malignant pulmonary nodules: a pilot study , 2017, World Journal of Surgical Oncology.

[18]  Yi Zhang,et al.  Tumor‐suppressive functions of long‐chain acyl‐CoA synthetase 4 in gastric cancer , 2016, IUBMB life.

[19]  Aamir Ahmad Epigenetics in Personalized Management of Lung Cancer. , 2016, Advances in experimental medicine and biology.

[20]  Aamir Ahmad,et al.  Lung Cancer and Personalized Medicine: Novel Therapies and Clinical Management. Preface. , 2016, Advances in experimental medicine and biology.

[21]  D. Ettinger,et al.  Non-Small Cell Lung Cancer, Version 6.2015. , 2015, Journal of the National Comprehensive Cancer Network : JNCCN.

[22]  D. Wood,et al.  National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Lung Cancer Screening. , 2015, Thoracic surgery clinics.

[23]  Fenghai Duan,et al.  Projected outcomes using different nodule sizes to define a positive CT lung cancer screening examination. , 2014, Journal of the National Cancer Institute.

[24]  Harry J de Koning,et al.  Lung cancer probability in patients with CT-detected pulmonary nodules: a prespecified analysis of data from the NELSON trial of low-dose CT screening. , 2014, The Lancet. Oncology.

[25]  Baljit Singh,et al.  Long Chain Fatty Acyl-CoA Synthetase 4 Is a Biomarker for and Mediator of Hormone Resistance in Human Breast Cancer , 2013, PloS one.

[26]  S. Lam,et al.  Probability of cancer in pulmonary nodules detected on first screening CT. , 2013, The New England journal of medicine.

[27]  Y. Nakanishi,et al.  Diagnostic value of CEA and CYFRA 21-1 tumor markers in primary lung cancer. , 2013, Lung cancer.

[28]  J. Sørensen,et al.  Carcinoembryonic antigen (CEA) as tumor marker in lung cancer. , 2012, Lung cancer.

[29]  A. Dasgupta,et al.  Diagnostic Role of Tumour Markers CEA, CA15-3, CA19-9 and CA125 in Lung Cancer , 2012, Indian Journal of Clinical Biochemistry.

[30]  P. Prorok,et al.  Lung cancer screening with low-dose helical CT: results from the National Lung Screening Trial (NLST) , 2011, Journal of medical screening.

[31]  C. Gatsonis,et al.  Reduced Lung-Cancer Mortality with Low-Dose Computed Tomographic Screening , 2012 .

[32]  N. Viñolas,et al.  Mucins CA 125, CA 19.9, CA 15.3 and TAG-72.3 as Tumor Markers in Patients with Lung Cancer: Comparison with CYFRA 21-1, CEA, SCC and NSE , 2008, Tumor Biology.

[33]  Feng Chen,et al.  [Clinical value of combined detection of serum tumor markers in lung cancer diagnosis]. , 2008, Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition.

[34]  S. Prescott,et al.  Fatty acid CoA ligase 4 is up-regulated in colon adenocarcinoma. , 2001, Cancer research.