N-Glycome changes reflecting resistance to platinum-based chemotherapy in ovarian cancer.,Journal of Proteomics

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N-Glycome changes reflecting resistance to platinum-based chemotherapy in ovarian cancer.
Journal of Proteomics ( IF 2.8 ) Pub Date : 2020-09-06 , DOI: 10.1016/j.jprot.2020.103964
Martina Zahradnikova ₁ , Ivana Ihnatova ₂ , Erika Lattova ₃ , Lukas Uhrik ₁ , Eliska Stuchlikova ₁ , Rudolf Nenutil ₁ , Dalibor Valik ₁ , Monika Nalezinska ₄ , Josef Chovanec ₄ , Zbynek Zdrahal ₃ , Borivoj Vojtesek ₁ , Lenka Hernychova ₁ , Milos V Novotny ₅

Affiliation

A number of studies have reported aberrant glycosylation in connection with malignancy. Our investigation further expands on this topic through the examination of N-glycans, which could be associated with the resistance of advanced stage, high-grade non-mucinous ovarian cancer to platinum/taxane based chemotherapy. We used tissue samples of 83 ovarian cancer patients, randomly divided into two independent cohorts (basic and validation). Both groups involved either cases with/without postoperative tumor residue or the cases determined either resistant or sensitive to this chemotherapy. In the validation cohort, preoperative serum samples were also available. N-glycans released from tumors and sera were permethylated and analyzed by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). The MS analysis yielded a consecutive detection of 68 (tissue) and 63 (serum) N-glycan spectral signals. Eight of these were found to be differentially abundant in tissues of both independent cohorts including the cases with a postoperative cancer residue. One of these glycans was detected as differentially abundant in sera of the validation cohort. No statistically significant differences in intensities due to the same N-glycans were found in the cases without postoperative macroscopic residues in either the basic or validation cohort.

From the biochemical point of view, the statistically significant N-glycans correspond to the structures carrying bisecting (terminal) GlcNAc residue and tetra-antennary structures with sialic acid and/or fucose residues. Among them, six tissue N-glycans could be considered potential markers connected with a resistance to chemotherapy in ovarian cancer patients. The prediction of primary resistance to standard chemotherapy may identify the group of patients suitable for alternative treatment strategies.

Significance

Drug resistance has become a major impediment to a successful treatment of patients with advanced ovarian cancer. The glycomic measurements related to cancer are becoming increasingly popular in identification of the key molecules as potential diagnostic and prognostic indicators. Our report deals with identification of differences in N-glycosylation of proteins in tissue and serum samples from the individuals showing sensitivity or resistance to platinum/taxane-based chemotherapy. The detection sensitivity to chemotherapy is vitally important for these patients.

中文翻译：

N-甘氨酸的变化反映了卵巢癌对铂类化学疗法的耐药性。

许多研究报道了与恶性肿瘤有关的异常糖基化。我们的研究通过检测N-聚糖进一步扩展了这一主题，N-聚糖可能与晚期，高度非粘液性卵巢癌对铂/紫杉烷类化学疗法的耐药性有关。我们使用了83例卵巢癌患者的组织样本，将其随机分为两个独立的队列（基本和验证）。两组均包括术后肿瘤残留/无肿瘤残留或确定对该化疗耐药或敏感的病例。在验证队列中，术前血清样品也可提供。将从肿瘤和血清中释放的N-聚糖过甲基化，并通过基质辅助激光解吸/电离质谱（MALDI-MS）进行分析。MS分析连续检测到68个（组织）和63个（血清）N-聚糖光谱信号。发现其中有八个在两个独立队列的组织中差异丰富，包括术后残留癌症的病例。在验证队列的血清中检测到这些聚糖之一差异丰富。在基本或验证队列中均无术后宏观残留的病例中，未发现由于相同的N-聚糖而导致强度发生统计学差异。

从生物化学的观点来看，统计学上显着的N-聚糖对应于带有二等分（末端）GlcNAc残基的结构和带有唾液酸和/或岩藻糖残基的四触角结构。其中，六个卵巢组织中的N-聚糖被认为是与卵巢癌患者的化疗耐药相关的潜在标志物。对标准化学疗法原发性耐药的预测可能会确定适合替代治疗策略的患者组。