Establishing prognostic models for intrahepatic cholangiocarcinoma based on immune cells

Zhuo-Ran Wang; Cun-Zhen Zhang; Zhan Ding; Yi-Zhuo Li; Jian-Hua Yin; Nan Li

doi:10.4251/wjgo.v16.i10.4092

Establishing prognostic models for intrahepatic cholangiocarcinoma based on immune cells

World J Gastrointest Oncol. 2024 Oct 15;16(10):4092-4103. doi: 10.4251/wjgo.v16.i10.4092.

Authors

Zhuo-Ran Wang^{1

2

3

4}, Cun-Zhen Zhang¹, Zhan Ding^{2

3

4}, Yi-Zhuo Li⁵, Jian-Hua Yin^{2

3

4}, Nan Li^{1

6}

Affiliations

¹ Department of Hepatic Surgery I (Ward I) Shanghai Eastern Hepatobiliary Surgery Hospital, Navy Medical University, Shanghai 200433, China.
² Key Laboratory of Biological Defense, Ministry of Education, Navy Medical University, Shanghai 200433, China.
³ Shanghai Key Laboratory of Medical Bioprotection, Navy Medical University, Shanghai 200433, China.
⁴ Department of Epidemiology, Faculty of Navy Medicine, Navy Medical University, Shanghai 200433, China.
⁵ Department of Oncology, 905 Hospital of People's Liberation Army Navy, Shanghai 200050, China.
⁶ Department of Hepatobiliary Surgery, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China. liparislisi@aliyun.com.

Abstract

Background: Intrahepatic cholangiocarcinoma (ICC) is a malignant liver tumor that is challenging to treat and manage and current prognostic models for the disease are inefficient or ineffective. Tumor-associated immune cells are critical for tumor development and progression. The main goal of this study was to establish models based on tumor-associated immune cells for predicting the overall survival of patients undergoing surgery for ICC.

Aim: To establish 1-year and 3-year prognostic models for ICC after surgical resection.

Methods: Immunohistochemical staining was performed for CD4, CD8, CD20, pan-cytokeratin (CK), and CD68 in tumors and paired adjacent tissues from 141 patients with ICC who underwent curative surgery. Selection of variables was based on regression diagnostic procedures and goodness-of-fit tests (PH assumption). Clinical parameters and pathological diagnoses, combined with the distribution of immune cells in tumors and paired adjacent tissues, were utilized to establish 1- and 3-year prognostic models.

Results: This is an important application of immune cells in the tumor microenvironment. CD4, CD8, CD20, and CK were included in the establishment of our prognostic model by stepwise selection, whereas CD68 was not significantly associated with the prognosis of ICC. By integrating clinical data associated with ICC, distinct prognostic models were derived for 1- and 3-year survival outcomes using variable selection. The 1-year prediction model yielded a C-index of 0.76 95% confidence interval (95%CI): 0.65-0.87 and the 3-year prediction model produced a C-index of 0.69 (95%CI: 0.65-0.73). Internal validation yielded a C-index of 0.761 (95%CI: 0.669-0.853) for the 1-year model and 0.693 (95%CI: 0.642-0.744) for the 3-year model.

Conclusion: We developed Cox regression models for 1-year and 3-year survival predictions of patients with ICC who underwent resection, which has positive implications for establishing a more comprehensive prognostic model for ICC based on tumor immune microenvironment and immune cell changes in the future.

Keywords: Biomarkers; Intrahepatic cholangiocarcinoma; Prediction models; Prognosis; Tumor immune cells.