Retrospective Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 21, 2023; 29(23): 3645-3657
Published online Jun 21, 2023. doi: 10.3748/wjg.v29.i23.3645
High expression of the circadian clock gene NPAS2 is associated with progression and poor prognosis of gastric cancer: A single-center study
Xiao-Meng Cao, Wen-Di Kang, Tian-Hong Xia, Shao-Bin Yuan, Chang-An Guo, Wen-Jie Wang, Hong-Bin Liu
Xiao-Meng Cao, Department of General Surgery, Gansu Provincial Hospital of TCM, Lanzhou 730050, Gansu Province, China
Xiao-Meng Cao, Shao-Bin Yuan, The First Clinical Medical College, Gansu University of Chinese Medicine, Lanzhou 730030, Gansu Province, China
Wen-Di Kang, Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
Tian-Hong Xia, Clinical Medicine College, Ningxia Medical University, Clinical Medicine college, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
Chang-An Guo, Department of Emergency, Lanzhou University Second Hospital, Lanzhou 730030, Gansu Province, China
Wen-Jie Wang, Department of General Surgery, Lanzhou University Second Hospital, Lanzhou 730030, Gansu Province, China
Hong-Bin Liu, Department of General Surgery, The 940th Hospital of Joint Logistics Support Force of Chinese People's Liberation Army, Lanzhou 730050, Gansu Province, China. 1554153823@qq.com
Author contributions: Cao XM and Kang WD contributed equally to this work and share first authorship; Cao XM, Kang WD, and Liu HB designed the project and reviewed and edited the manuscript; Cao XM and Kang WD analyzed the data and wrote the main manuscripts; Xia TH and Yuan SB carried out research selection and data collection; Guo CA, Wang WJ and Liu HB participated in the discussion of classification criteria.
Institutional review board statement: The studies involving human participants were reviewed and approved by Medical Ethics Committee of the Second Hospital of Lanzhou University, approval No. 2021A-561. The patients/participants provided written informed consent to participate in this study.
Informed consent statement: The Medical Ethics Committee of the Second Hospital of Lanzhou University waived the need for informed consent due to the retrospective nature of the study.
Conflict-of-interest statement: The authors declare no conflict of interest.
Corresponding author: Hong-Bin Liu, MD, Professor, Department of General Surgery, The 940th Hospital of Joint Logistics Support Force of Chinese People's Liberation Army, No. 333 Nanbinhe Road, Qilihe District, Lanzhou 730050, Gansu Province, China. 1554153823@qq.com
Received: February 9, 2023
Peer-review started: February 9, 2023
First decision: March 9, 2023
Revised: March 16, 2023
Accepted: May 4, 2023
Article in press: May 4, 2023
Published online: June 21, 2023
Processing time: 127 Days and 1 Hours
Abstract
BACKGROUND

The prognostic assessment of patients after surgical resection of gastric cancer (GC) patients is critical. However, the role of the circadian clock gene NPAS2 expression in GC remains unknown.

AIM

To explore the relationship between NPAS2 and the survival prognosis of GC patients and clarify its role in evaluating GC prognosis.

METHODS

The tumor tissues and clinical data of 101 patients with GC were collected retrospectively. Immunohistochemical staining (IHC) was used to detect the expression of NPAS2 protein in GC and adjacent tissues. Univariate and multivariate Cox regression analysis was used to determine the independent prognostic factors of GC, and a nomogram prediction model was established. The receiver operating characteristic (ROC) curve, the ROC area under the curve, the calibration curve, and C-index were used to evaluate the predictive effectiveness of the model. Kaplan Meier analysis was used to compare the risk stratification of subgroups according to the median score in the nomogram model of each patient.

RESULTS

Microarray IHC analysis showed that the positive rate of NPAS2 protein expression in GC tissues was 65.35%, which was significantly higher than 30.69% in adjacent tissues. The high expression of NPAS2 was correlated with tumor-node-metastasis (TNM) stage (P < 0.05), pN stage (P < 0.05), metastasis (P < 0.05), venous invasion (P < 0.05), lymphatic invasion (P < 0.05), and lymph node positive (P < 0.05) of GC. Kaplan Meier survival analysis showed that the 3-year overall survival (OS) of patients with high NPAS2 expression was significantly shortened (P < 0.0001). Univariate and multivariate COX regression analysis showed that TNM stage (P = 0.009), metastasis (P = 0.009), and NPAS2 expression (P = 0.020) were independent prognostic factors of OS in GC patients for 3 years. The nomogram prediction model based on independent prognostic factors has a C-Index of 0.740 (95%CI: 0.713-0.767). Furthermore, subgroup analysis showed that the 3-year OS time of the high-risk group was significantly lower than that of the low-risk group (P < 0.0001).

CONCLUSION

NPAS2 is highly expressed in GC tissues and is closely related to worse OS in patients. Therefore, the evaluation of NPAS2 expression may be a potential marker for GC prognosis evaluation. Notably, the nomogram model based on NPAS2 can improve the accuracy of GC prognosis prediction and assist clinicians in postoperative patient management and decision-making.

Keywords: NPAS2; Gastric cancer; Tissue microarray; Survival analysis; Prediction model; Nomogram

Core Tip: The prognostic assessment of patients after surgical resection of gastric cancer (GC) is critical. However, the role of NPAS2 expression in GC remains unknown. Our study identified for the first time that high NPAS2 protein expression was associated with poor overall survival prognosis in GC patients and was an independent risk factor for patients after radical resection of GC. We constructed a nomogram prediction model by combining NPAS2 and other clinically independent risk factors, thus improving the predictive accuracy of GC prognosis.