High Expression of F-Box Protein 43 Is Associated With Poor Prognosis and Adjuvant Chemotherapy Resistance in Colorectal Cancer

Junyu Liu; Xi Yang; Miao Li; Ying Ying Liu; Yulan Wang; Shichao Li; Fengping Zheng

doi:10.14740/wjon1642

High Expression of F-Box Protein 43 Is Associated With Poor Prognosis and Adjuvant Chemotherapy Resistance in Colorectal Cancer

World J Oncol. 2023 Aug;14(4):246-254. doi: 10.14740/wjon1642. Epub 2023 Aug 4.

Authors

Junyu Liu^{1

2}, Xi Yang^{3

2}, Miao Li^{4

2}, Ying Ying Liu⁵, Yulan Wang⁵, Shichao Li⁵, Fengping Zheng¹

Affiliations

¹ Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
² These authors contributed equally to this work.
³ Department of Medical Service, General Hospital of Xinjiang Military Command, Urumqi, Xinjiang, China.
⁴ School of Rehabilitation Medicine, Xinjiang Medical University, Urumqi, Xinjiang, China.
⁵ Depatment of Pathology, General Hospital of Xinjiang Military Command, Urumqi, Xinjiang, China.

Abstract

Background: The F-box protein 43 (FBXO43), also referred to as endogenous meiotic inhibitor 2 (EMI2), has been linked to the advancement of various types of cancer, such as hepatocellular carcinoma, breast cancer, cholangiocarcinoma, and gastric cancer. Nevertheless, the precise function of FBXO43 in colorectal cancer (CRC) remains unclear. This study employed data from The Cancer Genome Atlas (TCGA) and clinical specimens to analyze the expression, prognostic value, and chemotherapeutic advantages of FBXO43 in CRC.

Methods: Level 3 RNA sequencing data pertaining to 631 cases of colon and rectal adenocarcinomas (COAD-READ) were downloaded from TCGA. The data were utilized to analyze the expression, prognosis, and related signal pathways of FBXO43. The expression of FBXO43 in clinical samples was subsequently confirmed through the use of real-time quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC). Lastly, a tissue microarray (TMA) consisting of 120 cases of CRC and corresponding normal tissues was established to investigate the relationship between FBXO43 and survival outcomes.

Results: Results from both the TCGA analysis and clinical samples indicated that FBXO43 was significantly upregulated in CRC tissues in comparison to normal tissues. Moreover, high level of FBXO43 was found to be relevant to malignant clinical features, such as differentiation, lymph node metastasis, and pathological stage, as well as unfavorable prognosis in CRC patients. Subgroup analysis further demonstrated that FBXO43 could be an effective parameter for stratifying low-risk CRC patients. Notably, survival analysis showed that patients with high level of FBXO43 had worse overall survival (OS) and disease-free survival (DFS) following adjuvant chemotherapy, and FBXO43 was distinctly upregulated in chemotherapy-resistant patients' primary CRC tissues.

Conclusions: FBXO43 was upregulated and associated with poor prognosis of CRC; patients with high expression of FBXO43 may not be benefit from adjuvant chemotherapy.

Keywords: Chemotherapy; Colorectal cancer; FBXO43; Prognosis.