Reduction of novel circulating long-chain fatty acids in colorectal cancer patients is independent of tumor burden and correlates with age.
Reduction of novel circulating long-chain fatty acids in colorectal cancer patients is independent of tumor burden and correlates with age.
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DOI：
10.1186/1471-230x-10-140
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发表时间：
2010-11-29
影响因子：
2.4
通讯作者：
Goodenowe DB
中科院分区：
文献类型：
--
作者：
Ritchie SA;Heath D;Yamazaki Y;Grimmalt B;Kavianpour A;Krenitsky K;Elshoni H;Takemasa I;Miyake M;Sekimoto M;Monden M;Tomonaga T;Matsubara H;Sogawa K;Matsushita K;Nomura F;Goodenowe DB
与无疾病受试者相比，先前已显示治疗前CRC患者中新型羟基多不饱和超长链脂肪酸（hPULCFA）的血清水平降低，与疾病分期无关。然而，目前尚不清楚hPULCFAs水平的降低是否是由于癌症的存在，以及hPULCFAs在一般人群中的分布。进行以下研究以评估常规疗法是否会导致CRC患者中系统性hPULCFA的恢复，并研究hPULCFA水平与年龄之间的关系。使用串联质谱法测定以下群组中含28碳的hPULCFA C28H46O4（CRC-446）的血清水平：手术切除肿瘤后的两个独立的日本CRC人群（n = 86），手术后联合化疗/放疗后的北美高加索CRC队列（n = 150），990份随机选择的11 - 99岁受试者匿名血清样本，以及纵向收集的健康正常人血清样本（n = 8，长达90周）和IV期CRC受试者接受联合治疗（n = 12，长达63周）。CRC受试者的血清CRC-446水平显著低于对照组（对照组的平均值为0.297 ± 0.07 μ g/ml，CRC组为0.092 ± 0.03，p <0.001），并且不受手术肿瘤切除或化疗/放疗的影响（术前与术后之间p> 0.05）。在随机选择的990名受试者的队列中，CRC-446水平与年龄呈强负相关（p <E-11），在CRC阳性受试者中未观察到相关性。然而，纵向受试者内结果显示，在无疾病受试者和晚期CRC患者中，CRC-446水平在长达90周的短期内相对稳定。我们的研究结果表明，CRC-446水平不受常规CRC治疗的影响，并与年龄呈负相关，这表明血清CRC-446水平降低可能存在于CRC发展之前。结果外推到一个简单的筛查方案显示，与粪便血液检测相比，使用血清CRC-446水平进行结肠镜检查前筛查将需要减少80%的结肠镜检查，将识别50岁以下受试者的风险，并将导致早期病例检测数量的增加。这些血清代谢物在癌症发展病因学中的确切作用仍有待确定。
Serum levels of novel hydroxy polyunsaturated ultra long-chain fatty acids (hPULCFAs) have been previously shown to be reduced in pre-treatment CRC patients compared to disease-free subjects, independent of disease stage. However, whether reduced levels of hPULCFAs result from the presence of cancer is currently unknown, as is the distribution of hPULCFAs in the general population. The following studies were carried out to assess whether conventional therapy would result in restoration of systemic hPULCFAs in CRC patients, and to investigate the relationship between hPULCFA levels and age. Tandem mass spectrometry was used to determine serum levels of the 28 carbon-containing hPULCFA C28H46O4 (CRC-446) in the following cohorts: two independent Japanese CRC populations following surgical tumor removal (n = 86), a North American Caucasian CRC cohort (n = 150) following post-surgery combination chemo/radiation therapy, 990 randomly selected anonymized serum samples from subjects ranging between 11 and 99 years of age, as well as longitudinally collected serum samples from healthy normals (n = 8, up to 90 weeks) and stage IV CRC subjects on combination therapy (n = 12, up to 63 weeks). Serum CRC-446 levels in CRC subjects were significantly lower than controls (mean of 0.297 ± 0.07 ug/ml in controls versus 0.092 ± 0.03 in CRCs, p < 0.001), and were unaffected by surgical tumor removal or by chemo/radiation treatment (p > 0.05 between pre vs post surgery). CRC-446 levels showed a strong inverse association with age (p < E-11) across the randomly-selected cohort of 990 subjects, with no correlation observed in the CRC-positive subjects. Longitudinal intra-subject results, however, showed relatively stable CRC-446 levels over the short term of up to 90 weeks in both disease-free subjects and late-stage CRC patients. Our findings show that CRC-446 levels are not affected by conventional CRC treatment and inversely correlate with age, which suggest that reduced serum CRC-446 levels likely exist prior to the development of CRC. Extrapolation of the results to a simple screening scenario showed that, compared to fecal blood testing, pre-colonoscopy screening using serum CRC-446 levels would require 80% fewer colonoscopies, would identify risk in subjects under the age of 50, and would result in increased numbers of early cases detected. The precise role these serum metabolites play in the aetiology of cancer development remains to be determined.