Serum insulin-like growth factor binding protein-3 as a potential biomarker for diagnosis and prognosis of oesophageal squamous cell carcinoma

Yun Luo; Chao-Qun Hong; Bin-Liang Huang; Tian-Yan Ding; Ling-Yu Chu; Biao Zhang; Qi-Qi Qu; Xin-Hao Li; Can-Tong Liu; Yu-Hui Peng; Hai-Peng Guo; Yi-Wei Xu

doi:10.1080/07853890.2022.2104921

Serum insulin-like growth factor binding protein-3 as a potential biomarker for diagnosis and prognosis of oesophageal squamous cell carcinoma

Ann Med. 2022 Dec;54(1):2153-2166. doi: 10.1080/07853890.2022.2104921.

Authors

Yun Luo^{1

2}, Chao-Qun Hong³, Bin-Liang Huang^{1

2

4}, Tian-Yan Ding^{1

2}, Ling-Yu Chu^{1

2}, Biao Zhang^{1

2}, Qi-Qi Qu^{1

2}, Xin-Hao Li^{1

2}, Can-Tong Liu^{1

2

4}, Yu-Hui Peng^{1

2

4}, Hai-Peng Guo⁵, Yi-Wei Xu^{1

2

4}

Affiliations

¹ Department of Clinical Laboratory Medicine, the Cancer Hospital of Shantou University Medical College, Shantou, China.
² Precision Medicine Research Center, Shantou University Medical College, Shantou, China.
³ Department of Oncological Laboratory Research, the Cancer Hospital of Shantou University Medical College, Shantou, China.
⁴ Guangdong Esophageal Cancer Institute, Guangzhou, China.
⁵ Department of Head and Neck Surgery, the Cancer Hospital of Shantou University Medical College, Shantou, China.

Abstract

Background: Insulin-like growth factor binding protein-3 (IGFBP3) has been reported to be related to the risk of some cancers. Here we focussed on serum IGFBP3 as a possible biomarker of diagnosis and prognosis for oesophageal squamous carcinoma (ESCC).

Methods: Enzyme-linked immunosorbent assay (ELISA) was used to measure the serum IGFBP3 level in the training cohort including 136 ESCC patients and 119 normal controls and the validation cohort with 55 ESCC patients and 42 normal controls. The receiver operating characteristics curve (ROC) was used to assess the diagnosis value. Cox proportional hazards model was applied to select factors for survival nomogram construction.

Results: Serum IGFBP3 levels were significantly lower in early-stage ESCC or ESCC patients than those in normal controls (p < .05). The specificity and sensitivity of serum IGFBP3 for the diagnosis of ESCC were 95.80% and 50.00%, respectively, with the area under the ROC curve (AUC) of 0.788 in the training cohort. Similar results were observed in the validation cohort (88.10%, 38.18%, and 0.710). Importantly, serum IGFBP3 could also differentiate early-stage ESCC from controls (95.80%, 52.54%, 0.777 and 88.10%, 36.36%, 0.695 in training and validation cohorts, respectively). Furthermore, Cox multivariate analysis revealed that serum IGFBP3 was an independent prognostic risk factor (HR = 2.599, p = .002). Lower serum IGFBP3 level was correlated with reduced overall survival (p < .05). Nomogram based on serum IGFBP3, TNM stage, and tumour size improved the prognostic prediction of ESCC with a concordance index of 0.715.

Conclusion: We demonstrated that serum IGFBP3 was a potential biomarker of diagnosis and prognosis for ESCC. Meanwhile, the nomogram might help predict the prognosis of ESCC. Key MessageSerum IGFBP3 showed early diagnostic value in oesophageal squamous cell carcinoma with independent cohort validation. Moreover, serum IGFBP3 was identified as an independent prognostic risk factor, which was used to construct a nomogram with improved prognosis ability in oesophageal squamous cell carcinoma.

Keywords: ESCC serum biomarker; Serum insulin-like growth factor binding protein-3; diagnosis and prognosis; oesophageal squamous cell carcinoma.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers, Tumor
Carcinoma, Squamous Cell* / diagnosis
Esophageal Neoplasms* / diagnosis
Esophageal Squamous Cell Carcinoma* / diagnosis
Humans
Prognosis
ROC Curve

Substances

Biomarkers, Tumor

Grants and funding

This work was supported by the Natural Science Foundation of China [grant number 81972801]; Guangdong Basic and Applied Basic Research Foundation [grant number 2019A1515011873]; Guangdong Esophageal Cancer Institute Science and Technology Program [grant number Q201906]; Science and Technology Special Fund of Guangdong Province of China [grant number 210729156901797; 190829105556145] and the 2020 Li Ka Shing Foundation Cross-Disciplinary Research Grant [grant number 2020LKSFG01B].