Lipoproteins as Markers for Monitoring Cancer Progression

Maran, Logeswaran; Hamid, Aini Ismafairus Abd; Hamid, Shahrul Bariyah Sahul

doi:10.1155/2021/8180424

Cited by 12 publications

(16 citation statements)

References 62 publications

(106 reference statements)

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“…Actually, the associations between HDL-c levels and tumorigenesis or cancer development have been reported in endocrine-related cancers, such as prostate cancer, epithelial thyroid cancer, ovarian cancer, pancreatic cancer, adrenal and testicular cancer [ 18 ]. Similar association is also observed in other malignant tumors, such as gastric cancer, hepatocellular carcinoma, and lung adenocarcinoma [ 19 ]. A recent study reported that HDL-c levels are associated with malignant intraductal papillary mucinous neoplasms (IPMNs) [ 20 ].…”

Section: Introductionsupporting

confidence: 77%

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The associations between serum high-density lipoprotein cholesterol levels and malignant behavior in pancreatic neuroendocrine neoplasms

et al. 2022

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Background The role of serum high-density lipoprotein cholesterol (HDL-c) in tumorigenesis are observed in several endocrine-related cancers. However, its role in pancreatic neuroendocrine neoplasms (PNENs) has not been understood. In the current study, the relationship between HDL-c levels and malignant behavior in PNENs was explored. Methods One hundred ninety-seven patients with histopathology confirmed PNENs were included. PNENs were divided into three grades (G1, G2 and G3) as 2017 WHO classification based on ki67 index and mitosis count. The demographic data, clinical information, tumor morphological and pathological features (organs invasion, lymph node metastasis, vascular invasion and perineural invasion), and serum tumor biomarkers were collected. The relationships between HDL-c levels and malignant behaviors in PNENs were analyzed using logistic regression analysis. Models were also developed for the identification of high grade PNENs. Results The levels of serum HDL-c in G2/G3 tumor were significantly lower than that in G1 tumor (P = 0.031). However, no such difference was found between G3 and G1/G2. The proportions of low HDL-c (≤ 0.9 mmol/L) were higher in high-grade PNENs (G2/G3 or G3) than those in low-grade (G1 or G1/G2) (29.0 vs 15.2%, P = 0.032; 37.0 vs 20.5%, P = 0.023). The risk of G2/G3 tumors in patients with high serum HDL-c levels was decreased (odds ratio (OR) = 0.35, 95% confidence interval (CI): 0.12–0.99). Similarly, the risk of G3 PNENs increased in patients with low HDL-c levels (OR = 2.51, 95%CI:1.12–5.60). HDL-c level was also associated with a high ki67 index (> 55%) (OR = 0.10, 95%CI: 0.02–0.51) and neuroendocrine carcinoma G3 (OR = 0.21, 95%CI: 0.06–0.80). The area under the curve (AUC) of HDL-c + tumor size + age was 0.85 (95% CI: 0.79–0.91) in identifying G2/G3 PNENs, and HDL-c (> 0.9 mmol/L) + tumor size + age had an AUC of 0.77 (95% CI: 0.70–0.84) in identifying G3 PNENs. HDL-c level was associated with lymph node metastasis (OR = 0.24, 95%CI:0.08–0.99). Conclusion Serum HDL-c levels were significantly associated with malignant behaviors in PNENs, in particular to tumor grade and lymph node metastasis.

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Section: Introductionsupporting

confidence: 77%

“…Increasing evidence suggests that the cholesterol plays noticeable role in tumorigenesis and cancer progression [ 23 ]. Lipoproteins are also markers for monitoring cancer progression [ 19 ]. As one of the major components, HDL-c showed a meaningful correlation with cancer risk [ 24 – 32 ].…”

Section: Discussionmentioning

confidence: 99%

The associations between serum high-density lipoprotein cholesterol levels and malignant behavior in pancreatic neuroendocrine neoplasms

et al. 2022

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“…Type of ω- Circulating lipids were similar to those of BC patients in the control arm of a newly diagnosed EPA/DHA supplementation study [27]. In the same way, Non-HDL and total cholesterol values were comparable to those described in a general population of agematched women [28].…”

Section: Type Of Studiessupporting

confidence: 72%

“…Conversely, some authors suggest a positive association between HDL-C and BC risk in women with extensive mammographic density [22]. However, as described by Maran et al [27] generally a significant association is strongly suggested between LDL-C and carcinogenesis and oxidized-LDL and metastasis.…”

Section: Type Of Studiesmentioning

confidence: 94%

Link between Omega 3 Fatty Acids Carried by Lipoproteins and Breast Cancer Severity

et al. 2022

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According to the International Agency for Research on Cancer (IARC) more than 10% of cancers can be explained by inadequate diet and excess body weight. Breast cancer is the most common cancer affecting women. The goal of our study is to clarify the relationship between ω3 fatty acids (FA) carried by different lipoproteins and breast cancer (BC) severity, according to two approaches: through clinic-biological data and through in vitro breast cancer cell models. The clinical study has been performed in sera from a cohort of BC women (n = 140, ICO, France) whose tumors differed by their hormone receptors status (HR− for tumors negative for estrogen receptors and progesterone receptors, HR+ for tumors positive for either estrogen receptors or progesterone receptors) and the level of proliferation markers (Ki-67 ≤ 20% Prolif− and Ki-67 ≥ 30% Prolif+). Lipids and ω3FA have been quantified in whole serum and in apoB-containing lipoproteins (Non-HDL)) or free of it (HDL). Differences between Prolif− and Prolif+ were compared by Wilcoxon test in each sub-group HR+ and HR−. Results are expressed as median [25th–75th percentile]. Plasma cholesterol, triglycerides, HDL-cholesterol and Non-HDL cholesterol did not differ between Prolif− and Prolif+ sub-groups of HR− and HR+ patients. Plasma EPA and DHA concentrations did not differ either. In the HR− group, the distribution of EPA and DHA between HDL and Non-HDL differed significantly, as assessed by a higher ratio between the FA concentration in Non-HDL and HDL in Prolif− vs. Prolif+ patients (0.20 [0.15–0.36] vs. 0.04 [0.02–0.08], p = 0.0001 for EPA and 0.08 [0.04–0.10] vs. 0.04 [0.01–0.07], p = 0.04 for DHA). In this HR− group, a significant increase in Non-HDL EPA concentration was also observed in Prolif− vs. Prolif+ (0.18 [0.13–0.40] vs. 0.05 [0.02–0.07], p = 0.001). A relative enrichment on Non-HDL in EPA and DHA was also observed in Prolif− patients vs. Prolif+ patients, as assessed by a higher molar ratio between FA and apoB (0.12 [0.09–0.18] vs. 0.02 [0.01–0.05], p < 0.0001 for EPA and 1.00 [0.73–1.69 vs. 0.52 [0.14–1.08], p = 0.04 for DHA). These data were partly confirmed by an in vitro approach of proliferation of isolated lipoproteins containing EPA and DHA on MDA-MB-231 (HR−) and MCF-7 (HR+) cell models. Indeed, among all the studied fractions, only the correlation between the EPA concentration of Non-HDL was confirmed in vitro, although with borderline statistical significance (p = 0.07), in MDA-MB-231 cells. Non-HDL DHA, in the same cells model was significantly correlated to proliferation (p = 0.04). This preliminary study suggests a protective effect on breast cancer proliferation of EPA and DHA carried by apo B-containing lipoproteins (Non-HDL), limited to HR− tumors.

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“…Researchers revealed that statins showed a positive impact on the ICIs treatment outcome ( 13 ). The positive association of cancer risk and apoB level has been declared, while high LDL-C was suggested to be associated with high incidence of cancer and metastasis in most cancers ( 14 , 15 ). Recent studies indicated a positive correlation between LDL-C, HDL-C and serum cholesterol and the ICIs monotherapy response, whereas the contrary results were obtained in the chemotherapy groups ( 16 ).…”

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confidence: 99%

Serum cholesterol-riched apolipoprotein-B (apoB) containing lipoproteins predict the response to immune checkpoints inhibitors (ICIs) in non-small cell lung cancer (NSCLC) : A retrospective analysis

Zheng

et al. 2022

Preprint

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Background Lipid metabolism alternations reprogrammed tumor microenvironment (TME) to participate in clinical response to immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC). Body mass index (BMI), clinically used to assess body fat, has been positively correlated with ICIs monotherapy response. Circulating cholesterol is mainly packaged into apolipoproteins B (apoB) in the form of apoB containing lipoproteins, including low-density lipoprotein cholesterol (LDL-C) and remnant cholesterol (RC), which have been regarded as risk factors of tumorigenesis. The association between BMI, lipoproteins, and clinical outcome of ICIs is far from clear. Methods We performed a retrospective case-control analysis of 99 NSCLC patients treated with chemotherapy plus ICIs regimens in the department of oncology and lung cancer center of China-Japan Friendship Hospital between January 2019 to December 2021 and assessed the prognostic value of the BMI, serum lipids, lipoproteins, and apolipoproteins. Efficacy was assessed by response evaluation criteria in solid tumors (RECIST) version 1.1 and evaluated by the ICIs response (durable clinical benefit [DCB] / non-durable benefit [NDB]), best response (active/ non-active) and progression-free survival (PFS). The validation test and the mechanism exploration were performed with public data using bioinformatic methods. Results The contrary results to the ICIs single agents were obtained. BMI ≥ 25 kg/m2 was a risk indicator for NDB, non-active response to ICIs, shorter PFS with the confounders adjusted (OR = 6.06, 95% CI 2.05–19.89, p.val = 0.002; OR = 4.37, 95% CI 1.64–12.43, p.val = 0.004; HR = 3.08, 95% CI 1.63–5.82, p.val < 0.001). High cholesterol-riched apoB containing lipoproteins were risk factors for poor ICIs response. Low RC predicted the better ICIs response and the best response with the satisfied discriminative ability and the well-fitting calibration curves (OR = 0.12, 95%CI 0.02–0.63, p.val = 0.017; OR = 0.22. 95%CI 0.05–0.96, p.val = 0.047). Serum LDL-C predicted the longer PFS of ICIs with the added value to the BMI containing model (HR = 0.43, 95%CI 0.22–0.86, p.val = 0.016). Bioinformatic exploration in the TCGA-LUAD cohort showed that the APOB high group was infiltrated by elevated fibroblasts and other immune-suppressive cells to acquire the stromal barrier and form non-inflamed TME. Functional enrichment analysis indicated that the acquired ICIs resistance might be through the LRP6/5-Wnt-TGF-β axis which required laboratory experiments to verify. Conclusions In the NSCLC population treated with the combination of chemotherapy and ICIs, BMI ≥ 25 kg/m2, the elevated cholesterol-riched apoB containing lipoproteins are promise indicators for the poor ICIs response. Further large-scale validations and experimental explorations are needed.

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Lipoproteins as Markers for Monitoring Cancer Progression

Cited by 12 publications

References 62 publications

The associations between serum high-density lipoprotein cholesterol levels and malignant behavior in pancreatic neuroendocrine neoplasms

The associations between serum high-density lipoprotein cholesterol levels and malignant behavior in pancreatic neuroendocrine neoplasms

Link between Omega 3 Fatty Acids Carried by Lipoproteins and Breast Cancer Severity

Serum cholesterol-riched apolipoprotein-B (apoB) containing lipoproteins predict the response to immune checkpoints inhibitors (ICIs) in non-small cell lung cancer (NSCLC) : A retrospective analysis

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