Citation: Alvarez, M.R.; Zhou, Q.; Tena, J.; Barboza, M.; Wong, M.; Xie, Y.; Lebrilla, C.B.; Cabanatan, M.; Barzaga, M.T.; Tan-Liu, N.; et al. Glycomic, Glycoproteomic, and Proteomic Profiling of Philippine Lung Cancer and Peritumoral Tissues: Case Series Study of Patients Stages I–III. Cancers 2023, 15, 1559. https://doi.org/10.3390/ cancers15051559 Academic Editor: Jennifer Munkley Received: 30 October 2022 Revised: 20 February 2023 Accepted: 24 February 2023 Published: 2 March 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). cancers Article Glycomic, Glycoproteomic, and Proteomic Profiling of Philippine Lung Cancer and Peritumoral Tissues: Case Series Study of Patients Stages I–III Michael Russelle Alvarez 1,2 , Qingwen Zhou 1 , Jennyfer Tena 1 , Mariana Barboza 1,3 , Maurice Wong 1 , Yixuan Xie 1 , Carlito B. Lebrilla 1 , Michelle Cabanatan 4 , Ma. Teresa Barzaga 4,5 , Nelia Tan-Liu 4 , Francisco M. Heralde III 4,6 , Luster Serrano 2 , Ruel C. Nacario 2 and Gladys Cherisse Completo 2, * 1 Department of Chemistry, University of California Davis, Davis, CA 95616, USA 2 Institute of Chemistry, University of the Philippines Los Baños, Laguna 4031, Philippines 3 Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California Davis, Davis, CA 95616, USA 4 Molecular Diagnostics and Cellular Therapeutics Laboratory, Lung Center of the Philippines, Quezon City 1100, Philippines 5 College of Medicine, De La Salle Health Sciences Institute, Cavite 4114, Philippines 6 College of Medicine, University of the Philippines Manila, Manila City 1000, Philippines * Correspondence: gjcompleto@up.edu.ph Simple Summary: Protein glycosylation is a protein modification that contributes to a protein’s biological function. Over the years, it has been shown that protein glycosylation is correlated with cancer progression. Although much research has been performed on lung cancer protein glycosylation, clinical studies were conducted primarily on Caucasian populations. Hence, we are looking for protein glycosylation cancer biomarkers in a Philippine population, to identify which protein glycosylation modifications are unique to this population. Abstract: Lung cancer is the leading cause of cancer death and non-small cell lung carcinoma (NSCLC) accounting for majority of lung cancers. Thus, it is important to find potential biomarkers, such as glycans and glycoproteins, which can be used as diagnostic tools against NSCLC. Here, the N-glycome, proteome, and N-glycosylation distribution maps of tumor and peritumoral tissues of Filipino lung cancer patients (n = 5) were characterized. We present several case studies with varying stages of cancer development (I−III), mutation status (EGFR, ALK), and biomarker expression based on a three-gene panel (CD133, KRT19, and MUC1). Although the profiles of each patient were unique, specific trends arose that correlated with the role of aberrant glycosylation in cancer progression. Specifically, we observed a general increase in the relative abundance of high-mannose and sialofucosylated N-glycans in tumor samples. Analysis of the glycan distribution per glycosite revealed that these sialofucosylated N-glycans were specifically attached to glycoproteins involved in key cellular processes, including metabolism, cell adhesion, and regulatory pathways. Protein expression profiles showed significant enrichment of dysregulated proteins involved in metabolism, adhesion, cell−ECM interactions, and N-linked glycosylation, supporting the protein glycosylation results. The present case series study provides the first demonstration of a multi-platform mass- spectrometric analysis specifically for Filipino lung cancer patients. Keywords: Filipino; lung cancer; glycomics; proteomics; glycoproteomics 1. Introduction Despite advancements in cancer treatments, global cancer incidence, and mortality are still growing, reflecting several factors which include aging, population growth, cancer risk factors, and socioeconomic development. Of the estimated 19.3 million new cases and Cancers 2023, 15, 1559. https://doi.org/10.3390/cancers15051559 https://www.mdpi.com/journal/cancers