Fatty Acid Binding Protein 1 is an Independent Prognostic Biomarker for Gallbladder Cancer with Direct Hepatic Invasion

Shimei Qiu; Zhaonan Liu; Jun Hu; Ziyi Wang; Zhuying Yue; Ziheng Jia; Wenhua Zhang; Ziru Xue; Zebing Liu; Yingbin Liu

doi:10.7150/ijms.93413

Fatty Acid Binding Protein 1 is an Independent Prognostic Biomarker for Gallbladder Cancer with Direct Hepatic Invasion

Int J Med Sci. 2024 Mar 25;21(5):862-873. doi: 10.7150/ijms.93413. eCollection 2024.

Authors

Shimei Qiu^{1

2

3}, Zhaonan Liu², Jun Hu⁴, Ziyi Wang², Zhuying Yue³, Ziheng Jia², Wenhua Zhang¹, Ziru Xue¹, Zebing Liu⁵, Yingbin Liu^{1

2

3}

Affiliations

¹ School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, China.
² Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
³ State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200032, China.
⁴ Department of Animal Science and Technology, Shanghai Vocational College of Agriculture and Forestry, Shanghai, 201699, China.
⁵ Department of Pathology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.

Abstract

Background: Direct liver invasion (DI) is a predominant pathway of gallbladder cancer (GBC) metastasis, but the molecular alterations associated with DI remain addressed. This study identified specific genes correlated with DI, which may offer a potential biomarker for the diagnosis and prognosis of advanced GBC. Methods: RNA samples from 3 patients with DI of GBC were used for RNA-seq analysis. Differentially expressed genes and metabolic pathways between primary tumor (T) and DI tissue was used to analyze aberrant gene expressions. Immunohistochemistry (IHC) of fatty acid binding protein 1 (FABP1) in 62 patients with DI was engaged to evaluate its association with clinicopathological characteristics and prognosis. IHC of CD3⁺ and CD8⁺ T cells was analyzed for their correlation with FABP1 expression, clinicopathological features and prognosis. Univariate and multivariate Cox hazards regression analyses were performed to identify independent prognostic factors for disease-free survival (DFS) and overall survival (OS). Results: FABP1 mRNA levels were significantly upregulated in DI region compared to T tissue. IHC results showed identical results with elevated FABP1 (p < 0.0001). Expression of FABP1 in DI region was significantly associated with lymph node metastasis (P = 0.028), reduced DFS (P = 0.013) and OS (P = 0.022); in contrast, its expression in T region was not associated with clinicopathological characteristics and prognosis (P > 0.05). The density of CD8⁺ T cells in DI region with higher FABP1 expression was significantly lower than that with lower FABP1 expression (p = 0.0084). Multivariate analysis unveiled those hepatic metastatic nodules (HR = 3.35, 95%CI: 1.37-8.15, P = 0.008) and FABP1 expression in DI region (HR = 2.01, 95%CI: 1.05-3.88, P = 0.036) were high risk factors for OS, and FABP1(HR = 2.05, 95%CI: 1.04-4.06, P = 0.039) was also a high risk factor for DFS. Conclusions: Elevated expression of FABP1 in DI region serves as a potential prognostic biomarker for advanced GBC with DI.

Keywords: Direct Hepatic Invasion; FABP1; Gallbladder cancer; Metastasis; Prognosis.

MeSH terms

CD8-Positive T-Lymphocytes
Carcinoma in Situ*
Carcinoma*
Fatty Acid-Binding Proteins / genetics
Gallbladder Neoplasms* / genetics
Humans
Liver
Prognosis

Substances

Fatty Acid-Binding Proteins
FABP1 protein, human