Carbohydrate antigens Lewis a and Lewis b act as tumor markers cooperating with CA19.9 in the management of PDAC patients

IF 3.2 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY Clinica Chimica Acta Pub Date : 2024-10-04 DOI:10.1016/j.cca.2024.119990

Rossella Indellicato , Michele Dei Cas , Aida Zulueta , Anna Caretti , Delfina Tosi , Claudia Cigala , Gaetano Bulfamante , Enrico De Nicola , Giovanna Scifo , Enrico Opocher , Daniela Pistillo , Gennaro Nappo , Alessandro Zerbi , Marco Trinchera

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Abstract

Background

CA19.9 is the unique marker recommended for the preoperative staging and the follow-up of patients suffering from pancreatic ductal adenocarcinoma (PDAC) but up to 30% of PDAC patients maintain normal CA19.9 values and cannot be monitored in this way. Lewis a (Lea Galβ1,3[Fucα1,4]GlcNAc) and b (Leb, Fucα1,2Galβ1,3[Fucα1,4]GlcNAc) are antigens which are structurally similar to sialyl-Lewis a (Siaα2,3Galβ1,3[Fucα1,4]GlcNAc), the epitope of CA19.9.

Methods

We set an ELISA procedure determining the levels of Lea, Leb, and CA19.9 in the blood of healthy individuals or PDAC patients. Moreover, such antigens were also detected in cancer resections by immunofluorescence microscopy, and the levels of glycosyltransferase transcripts involved in Lewis antigen biosynthesis were determined by RT-qPCR.

Results

In our cohort of 116 healthy individuals, the distribution of circulating Lea and Leb was similar to that of CA19.9, allowing us to set putative cutoff values for both antigens. In a cohort of 115 PDAC patients, the differential distribution with respect to the controls was statistically significant for both antigens (p < 0.001). Out of 37 patients presenting normal CA19.9 values, 15 patients presented Lea or Leb above the cutoffs. By immunofluorescence, Lea, Leb and CA19.9 were all detected in cancer resections and expression levels were heterogeneous among patients in terms of intensity, localization and diffusion. The levels of relevant glycosyltransferase transcripts were found to be heterogeneous between cancers of different patients and no association was detectable with the levels of any circulating antigen.

Conclusions

The concurrent quantification of Lea and Leb together with CA19.9 improves the management of PDAC patients.

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碳水化合物抗原 Lewis a 和 Lewis b 可作为肿瘤标记物，与 CA19.9 配合用于 PDAC 患者的治疗。

背景：CA19.9 是推荐用于胰腺导管腺癌（PDAC）患者术前分期和随访的唯一标记物，但多达 30% 的 PDAC 患者的 CA19.9 值保持正常，无法通过这种方法进行监测。Lewis a（Lea Galβ1,3[Fucα1,4]GlcNAc）和 b（Leb，Fucα1,2Galβ1,3[Fucα1,4]GlcNAc）是与 CA19.9 的表位--硅氨酰-Lewis a（Siaα2,3Galβ1,3[Fucα1,4]GlcNAc）结构相似的抗原：我们采用 ELISA 方法测定健康人或 PDAC 患者血液中 Lea、Leb 和 CA19.9 的水平。此外，我们还通过免疫荧光显微镜在癌症切片中检测了这些抗原，并通过 RT-qPCR 测定了参与路易斯抗原生物合成的糖基转移酶转录物的水平：在我们的 116 例健康人队列中，循环 Lea 和 Leb 的分布与 CA19.9 相似，因此我们可以为这两种抗原设定推定的临界值。在一组 115 例 PDAC 患者中，与对照组相比，两种抗原的分布差异均有统计学意义（p 结论）：同时定量检测 Lea 和 Leb 以及 CA19.9 可改善 PDAC 患者的管理。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinica Chimica Acta 医学-医学实验技术

CiteScore

10.10

自引率

2.00%

发文量

1268

审稿时长

23 days

期刊介绍： The Official Journal of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Clinica Chimica Acta is a high-quality journal which publishes original Research Communications in the field of clinical chemistry and laboratory medicine, defined as the diagnostic application of chemistry, biochemistry, immunochemistry, biochemical aspects of hematology, toxicology, and molecular biology to the study of human disease in body fluids and cells. The objective of the journal is to publish novel information leading to a better understanding of biological mechanisms of human diseases, their prevention, diagnosis, and patient management. Reports of an applied clinical character are also welcome. Papers concerned with normal metabolic processes or with constituents of normal cells or body fluids, such as reports of experimental or clinical studies in animals, are only considered when they are clearly and directly relevant to human disease. Evaluation of commercial products have a low priority for publication, unless they are novel or represent a technological breakthrough. Studies dealing with effects of drugs and natural products and studies dealing with the redox status in various diseases are not within the journal''s scope. Development and evaluation of novel analytical methodologies where applicable to diagnostic clinical chemistry and laboratory medicine, including point-of-care testing, and topics on laboratory management and informatics will also be considered. Studies focused on emerging diagnostic technologies and (big) data analysis procedures including digitalization, mobile Health, and artificial Intelligence applied to Laboratory Medicine are also of interest.