Impact of Serum Apolipoprotein A-I on Prognosis and Bevacizumab Efficacy in Patients with Metastatic Colorectal Cancer: a Propensity Score-Matched Analysis

Abstract

PURPOSE: We aimed to investigate the role of apolipoprotein A-I (ApoA-I) as a predictor of prognosis and treatment efficacy of bevacizumab in patients with metastatic colorectal cancer (mCRC) treated with first-line chemotherapy with or without bevacizumab. METHODS: We conducted a retrospective study on consecutive patients who were diagnosed with mCRC at Sun Yat-sen University Cancer Center. According to their pretreatment ApoA-I level, patients were divided into low– and high–ApoA-I groups. Propensity score-matched method was performed to balance baseline characteristics between two groups. Based on whether they accepted bevacizumab as a first-line therapy, patients were further divided into the chemo + bevacizumab group and the chemo group. Overall survival (OS) and progression-free survival (PFS) were assessed with Kaplan-Meier method, log-rank test, and Cox regression. RESULTS: The optimal cutoff value for the ApoA-I level was determined to be 1.105 g/l. In the propensity-matched cohort of 508 patients, low ApoA-I was significantly associated with inferior OS (P < .001) and PFS (P < .001) than high ApoA-I. Multivariate analysis showed that ApoA-I level was an independent prognostic maker of OS (P < .001) and PFS (P = .001). PFS (P < .001) in either the high– or low–ApoA-I groups could be extended significantly after the administration of bevacizumab, and patients with a high ApoA-I level also had a better OS in the chemo + bevacizumab group than the chemo group (P = .049). CONCLUSIONS: Patients with a low ApoA-I level have poor prognoses, and they did not display an OS benefit from bevacizumab.

Association Between Pretreatment Serum Apolipoprotein A1 and Prognosis of Solid Tumors in Chinese Population: A Systematic Review and Meta-Analysis

“…These cancers included gastric cancer (GC) [27], bladder cancer [28], non small cell lung cancer (NSCLC) [29, 38], nasopharyngeal carcinoma (NPC) [30, 39], breast cancer [31, 32], colorectal cancer (CRC) [33], upper tract urothelial carcinoma (UTUC) [34], esophageal squamous cell cancer (ESCC) [35], renal cell carcinoma (RCC) [36], and hepatocellular carcinoma (HCC) [37]. Eleven studies were published in English [27-33, 35-37, 39], whereas the other two studies were in Chinese [34, 39]. One of these studies contained two cohorts [37].…”

“…The outcomes of OS were reported in all 14 cohorts, and the end points of DFS were presented in 4 cohorts [30-32, 36]. Nine cohorts recruited patients with all disease stages (stage I – IV) [27, 29, 30, 32, 34-37], three cohorts included patients with advanced stage (including stage IV [33, 39], and stage IIB – IV [38]), one cohort contained patients with stage I – III [31], and the other one reported the data of patient with stage Tis – T1 [28]. The median follow-up time ranged from 20.3 months to 89 months, and even five studies did not report it.…”

“…The primary treatments extremely varied among the 14 cohorts. These treatments included surgery [27, 28, 31, 32, 34-37], chemotherapy [33, 39], radiotherapy [30], and mixed treatment [29, 38]. The HRs and their 95% CIs in 11 cohorts were directly extracted from multivariate analyses, while those of the other cohorts were obtained from univariate analyses [27, 29, 31].…”

Prognostic value of the serum apolipoprotein B to apolipoprotein A-I ratio in metastatic colorectal cancer patients

“…A recent retrospective study reported that low serum ApoA-I levels were associated with advanced T class and TNM stage and systemic inflammation biomarkers in CRC. All of these findings indicate that serum ApoA-I may participate in multiple processes in the occurrence and development of cancers [19,20,[29][30][31].…”

“…Apolipoprotein A-I (ApoA-I), mainly synthesized in the liver and the small intestine, is a major fraction of HDL-C, accounting for approximately 70% [17,18]. In CRC patients, the serum ApoA-I level has been reported to be an independent prognostic indicator to predict chemotherapy efficacy and survival time [19][20][21][22][23]. On the other hand, apolipoprotein B (ApoB), an important blood apolipoprotein existing mostly in LDL-C and very-low-density lipoprotein cholesterol (VLDL-C), has been paid less attention to in CRC than ApoA-I.…”