F-Box蛋白43的高表达与结直肠癌的不良预后和辅助化疗耐药相关。

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

作者信息

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

机构信息

Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.

These authors contributed equally to this work.

出版信息

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

DOI:10.14740/wjon1642

PMID:37560338

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10409561/

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.

摘要

背景

F盒蛋白43（FBXO43），也被称为内源性减数分裂抑制因子2（EMI2），与多种类型癌症的进展有关，如肝细胞癌、乳腺癌、胆管癌和胃癌。然而，FBXO43在结直肠癌（CRC）中的具体功能仍不清楚。本研究利用来自癌症基因组图谱（TCGA）的数据和临床标本，分析FBXO43在CRC中的表达、预后价值和化疗优势。

方法

从TCGA下载了631例结肠和直肠腺癌（COAD-READ）的3级RNA测序数据。这些数据用于分析FBXO43的表达、预后及相关信号通路。随后通过实时定量聚合酶链反应（qPCR）和免疫组织化学（IHC）证实临床样本中FBXO43的表达。最后，建立了一个由120例CRC病例和相应正常组织组成的组织微阵列（TMA），以研究FBXO43与生存结果之间的关系。

结果

TCGA分析和临床样本的结果均表明，与正常组织相比，CRC组织中FBXO43显著上调。此外，发现FBXO43的高水平与恶性临床特征相关，如分化、淋巴结转移和病理分期，以及CRC患者的不良预后。亚组分析进一步表明，FBXO43可能是对低风险CRC患者进行分层的有效参数。值得注意的是，生存分析表明，FBXO43水平高的患者在辅助化疗后的总生存期（OS）和无病生存期（DFS）较差，并且FBXO43在化疗耐药患者的原发性CRC组织中明显上调。