Preoperative apolipoprotein B/A1 ratio is an independent prognostic factor in metastatic renal cell carcinoma

https://doi.org/10.1016/j.urolonc.2018.11.010Get rights and content

Highlights

  • A high preoperative apolipoprotein B/apolipoprotein A1 (Apo B/A1) ratio is significantly associated with poor PFS and OS in patients with metastatic renal cell carcinoma.

  • Preoperative Apo B/A1 ratio is an independent prognostic factor for PFS and OS in patients with metastatic renal cell carcinoma.

  • Preoperative Apo B/A1 ratio can be utilized as a novel prognostic biomarker for patients with metastatic renal cell carcinoma.

Abstract

Objectives

We aimed to explore the prognostic value of preoperative apolipoprotein B/apolipoprotein A1 (Apo B/A1) ratio in metastatic renal cell carcinoma (mRCC).

Materials and methods

Between January 2006 and December 2016, patients with mRCC who underwent cytoreductive nephrectomy at the Chinese PLA General Hospital were enrolled. The clinical-pathological parameters were collected retrospectively, and the preoperative Apo B/A1 ratios of two different subgroups were compared. The cut-off value was determined with the receiver operating characteristic (ROC) curve. The value of preoperative Apo B/A1 ratio on oncological outcome was determined through Kaplan–Meier survival analysis and Cox regression analysis.

Results

A total of 287 mRCC patients were enrolled in this study. The median postoperative follow-up time was 27.8 months (IQR, 12.5–58.6 months). The Apo B/A1 ratio was higher in the high Fuhrman grade (G3 and G4) group than that in the low Fuhrman grade (G1 and G2) group (P = 0.010). The area under the curve values of the ROC curves were 0.613 for progression-free survival (PFS) (P = 0.005) and 0.607 for overall survival (OS) (P = 0.004). The optimal cut-off values of Apo B/A1 ratio were 0.977 for PFS and 0.847 for OS. A high preoperative Apo B/A1 ratio (PFS ≥ 0.977; OS ≥ 0.847) was significantly associated with poor PFS (P < 0.0001) and OS (P = 0.0005). Cox regression analyses showed that the Apo B/A1 ratio is an independent prognostic factor for PFS (hazard ratio [HR] = 3.131; 95% confidence interval [CI] = 2.249–4.360; P < 0.001) and OS (HR = 2.173; 95% CI = 1.533–3.080; P < 0.001).

Conclusion

Preoperative Apo B/A1 ratio is an independent prognostic factor for PFS and OS in patients with mRCC. Preoperative Apo B/A1 ratio can be useful in improving current prognostic evaluation and treatment decision for patients with mRCC.

Introduction

Kidney cancer is among the 10 most common human malignancies in men and women [1], [2]. According to statistics, approximately 65,340 new cases and 14,970 deaths are related to this malignancy in 2018 in the United States [3]. Renal cell carcinoma (RCC), which is derived from renal tubular epithelial cells, is the most common histological type and accounts for over 80% of all cases [1], [2], [4], [5]. Approximately more than 15% of all RCC patients are diagnosed with metastatic renal cell carcinoma (mRCC) [1], [3], [6], and over 20% of patients with localized RCCs have metastases after partial or radical nephrectomy [7]. Metastatic RCC is a highly aggressive cancer with poor prognosis and currently have less than 8% 5-year survival rate [5], [8]. Moreover, mRCC requires systemic therapy and close follow-up is highly recommended owing to its biological characteristics [1], [2], [5], [9], [10], [11]. Methods that can accurately predict and evaluate the prognosis of mRCC have attracted considerable interest. For the past few years, an increasing number of valuable models and molecules for the prognosis prediction have been discovered, including the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic model [12], Memorial Sloan-Kettering Cancer Center (MSKCC) prognostic model [13], and others [14], [15], [16], [17], [18]. However, different clinical–pathological features result in different oncological outcomes, and even patients with comparable parameters can have highly different prognosis. Thus, novel easy-to-detect markers that can predict prognosis for patients with metastatic RCCs are needed.

Apolipoprotein A1 (Apo A1) and apolipoprotein B (Apo B) are two predominant components of high-density lipoprotein (HDL) and low-density lipoprotein (LDL), which have long been regarded to have extensive connections with cardiovascular disease [19], [20], diabetes [21], and Alzheimer's disease [22], [23]. In the field of tumor research, several experimental studies have showed that Apo A1 suppresses tumor cell growth both in vitro and in vivo, these tumors including colorectal cancer [24], [25], breast cancer [26], and melanoma [27]. Many studies that based on clinical data have reported that high Apo A1 level is associated with better prognosis in cancers, which including breast cancer [28], esophageal cancer [29], nasopharyngeal cancer [30], colorectal cancer [31], [32], bladder cancer [33], and renal cancer [34]. Apo B contains two subtypes, Apo B-48 and Apo B-100. Existing studies have showed that the Apo B and their mRNA editing enzymes are transcriptionally regulated by tumor suppressor gene p53 [35] and are involved in tumorigenesis [36]. For a long time, Apo B/Apo A1 (Apo B/A1) ratio was used as a risk index for cardiovascular disease [37]. Recently, several clinical studies have reported that Apo B/A1 ratio have potential values for the prognosis prediction of some kind of neoplasms, such as gastric cancer [38] and colorectal cancer [32]. However, the value of preoperative Apo B/A1 ratio in the prognostic evaluation of mRCC is still unclear.

In this study, we explore the association between preoperative Apo B/A1 ratio and the clinical–pathological features and evaluate the prognostic value of preoperative Apo B/A1 ratio in mRCC.

Section snippets

Patient population

This study was performed after obtaining the authorization of Ethics Committee of Chinese PLA General Hospital. Patients who conformed to the inclusion criteria between January 2006 and December 2016 were enrolled consecutively. The inclusion criteria for all the mRCC patients were listed below: (1) patients were diagnosed with mRCC, and underwent cytoreductive nephrectomy at the Urology Department of Chinese PLA General Hospital; (2) specimens were pathologically confirmed to be RCC by senior

Patient and clinical–pathological features

This study totally enrolled 287 mRCC patients. The detailed clinical–pathological characteristics are shown in Table 1. All enrolled patients underwent cytoreductive nephrectomy at our hospital. The median age of the 287 mRCC patients was 56 years (IQR, 47–64 years). The median body mass index (BMI) was 23.8 kg/m2 (IQR, 21.7–26.1 kg/m2). The median Apo B/A1 ratio was 0.859 (IQR, 0.686–1.083). Fatty liver was present in 75 (26.1%) patients. Regional lymph node metastasis was present in 98

Discussion

Despite the latest achievements in genetic and molecular biological research, the prognostic evaluation of RCC is still dependent on anatomical, histological, clinical, and molecular factors [11], [39], [40], [41], [42]. The biological association between circulating lipid levels and cancer risk has been confirmed [43], [44]. The two most common circulating lipids, namely, Apo A1 and Apo B, are identified as novel hematological biomarkers for the prognosis of many cancer types.

Apo A1, which is

Conclusion

Our study demonstrated that high preoperative Apo B/A1 ratio is significantly connected with poor PFS and OS in patients with mRCC. The preoperative Apo B/A1 ratio is an independent prognostic factor for both PFS and OS in mRCC. Metastatic RCC patients with high levels of preoperative Apo B/A1 ratio must receive considerable attention and must be subjected to consistent follow-up. As a novel prognostic factor, the preoperative Apo B/A1 ratio can be utilized as a supplement to improve the

References (47)

  • Q Quan et al.

    Impact of serum apolipoprotein a-i on prognosis and bevacizumab efficacy in patients with metastatic colorectal cancer: a propensity score-matched analysis

    Transl Oncol

    (2017)
  • L Lind

    Apolipoprotein B/A1 and risk of cardiovascular disease

    Lancet (London, England)

    (2008)
  • BC Leibovich et al.

    Predicting oncologic outcomes in renal cell carcinoma after surgery

    Eur Urol

    (2018)
  • A Verbiest et al.

    Molecular subtypes of clear-cell renal cell carcinoma are prognostic for outcome after complete metastasectomy

    Eur Urol

    (2018)
  • L Tosco et al.

    Survival and impact of clinical prognostic factors in surgically treated metastatic renal cell carcinoma

    Eur Urol

    (2013)
  • M Sun et al.

    Prognostic factors and predictive models in renal cell carcinoma: a contemporary review

    Eur Urol

    (2011)
  • Q Liu et al.

    Targeting lipid metabolism of cancer cells: a promising therapeutic strategy for cancer

    Cancer Lett

    (2017)
  • PD Chandler et al.

    Lipid biomarkers and long-term risk of cancer in the Women's Health Study

    Am J Clin Nutr

    (2016)
  • PC Barata et al.

    Treatment of renal cell carcinoma: current status and future directions

    CA Cancer J Clin

    (2017)
  • RL Siegel et al.

    Cancer statistics, 2018

    CA Cancer J Clin

    (2018)
  • JJ Hsieh et al.

    Renal cell carcinoma

    Nat Rev Dis Primers

    (2017)
  • TK Choueiri et al.

    Systemic therapy for metastatic renal-cell carcinoma

    New Engl J Med

    (2017)
  • A Mejean et al.

    Sunitinib alone or after nephrectomy in metastatic renal-cell carcinoma

    New Engl J Med

    (2018)
  • Funding: This study is supported by Beijing Natural Science Foundation (grant number: 7184244).

    Conflict of interest: No potential conflicts of interest were disclosed.

    1

    Fan Zhang, Yongpeng Xie, and Xin Ma contributed equally to this research as co-first authors.

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