N-glycan MALDI Imaging Mass Spectrometry on Formalin-Fixed Paraffin-Embedded Tissue Enables the Delineation of Ovarian Cancer Tissues

Abstract

Ovarian cancer is a fatal gynaecological malignancy in adult women with a five-year overall survival rate of only 30%. Glycomic and glycoproteomic profiling studies have reported extensive protein glycosylation pattern alterations in ovarian cancer. Therefore, spatio-temporal investigation of these glycosylation changes may unearth tissue-specific changes that occur in the development and progression of ovarian cancer. A novel method for investigating tissue-specific N-linked glycans is using matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) on formalin-fixed paraffinembedded ( Ovarian cancer is the fifth most fatal malignancy in adult women with an estimated 21,290 new cases diagnosed and 14,180 deaths recorded in the United States during 2015 (1). There are several reasons for the poor prognosis of ovarian cancer and its diagnosis at advanced stage-lack of diagnostic markers for the early detection (2, 3), rapid metastasis of the disease (4), and limited or modest understanding of the etiology, origin and the diverse clinical and pathological behavior of the tumors (5). Moreover, epithelial ovarian cancer comprises of several distinct sub-types based on their histopathological features into serous, endometrioid, clear-cell, mucinous, and undifferentiated subtypes (6, 7).Protein glycosylation is an important post-translational modification which has relevance in many biological processes such as cell signaling, immune responses, extracellular interaction and cell adhesion (8, 9). Aberrant protein glycosylation such as the expression of truncated glycans as well From the ‡Faculty

Tissue glycomics distinguish tumour sites in women with advanced serous adenocarcinoma

“…It is therefore not surprising that this close association between these serous cancers was also reflected in their membrane protein N ‐ and O ‐glycomic profiles, as evidenced broadly by the similar abundance when grouped into their glycan types. It is also interesting to note that the membrane proteins of the tumour tissues displayed abundant sialylation, a feature that has also been observed in a recent study using high‐resolution MALDI‐MS imaging (Everest‐Dass et al ., ). In this study, the authors noted, however, that the mono‐ and disialylated glycans were predominantly located in the stromal region of ovarian tumour tissue cross‐sections.…”

Recent Advances in the Mass Spectrometry Methods for Glycomics and Cancer

“…A similar approach using MALDI with ion mobility MS found high-mannose N-glycans expressed in FFPE ovarian cancer tissues. 48 A new method for MALDI imaging combining IR MALDI with ESI (IR MALDESI) has been used by Nazari and Muddiman to image cancerous chicken ovarian tissues, although glycans were not directly examined. 49 …”

Mass Spectrometry Imaging: A Review of Emerging Advancements and Future Insights

“…31,33,222,229,239 This trend is especially true for clinically inventoried samples, since strategies for analyzing FFPE tissue samples are in high demand. 49,51,100,213 For example, tissue microarrays, which are usually FFPE samples, provide unique opportunities for researchers to perform high-throughput screening of different diseases with little variation in preparation. 51,211 Beyond FFPE, one unique application of MSI on a mammalian tissue sample has been where cannabinoids, such as THC, and other drugs have been imaged with MS and MS/MS on single hair samples, which has promise for integration into toxicology-based screenings (Figure 7).…”

“…Briefly, MSI has shown applicability to determining metal accumulation, 226 discriminating tumor regions, 41,49,51,212,213 disease diagnosis, 218,248 and even intraoperative usage. 5,6 MS has already found its way into real-time surgeries with the invention of the iKnife, 70 and it is only a matter of time before MSI is utilized in a similar fashion.…”