Ras-Related Protein Rab-27B), RAB2B (Ras-Related Protein Rab-2B), RAB3B (Ras-Related Protein Rab-3B), RAB9A (Ras-Related Protein Rab-9A), RAB11B (Ras-Related Protein Rab-11B), STX11A (Syntaxin 11A), and VAMP7 (Vesicle Associated Membrane Protein 7) genes in 100 cancer and 60 adjacent non neoplastic fresh-frozen tissue specimens, which were prospectively collected from CRC patients (stages I-IV), surgically managed in the University Hospital of Patras, Greece. The quantification of mRNA expression was performed by using real-time qPCR and specific primers and probes. The mRNA levels were associated with clinicopathological parameters as well as with the clinical outcome of patients.Results: Gene expression of the studied molecules differed significantly between cancer and non-cancer tissues, with cancer tissues having lower levels of RAB27A, RAB27B, VAMP7 and RAB3B and higher levels of STX11A compared to non-neoplastic, tumor-adjacent tissues (p¼0.003, p¼0.014, p¼0.017, p RAB27A, RAB27B and RAB9A compared to patients without distant metastases (p¼0.049, p¼0.033 and p¼0.034, respectively). Furthermore, survival outcome was associated with gene expression of RAB27A, RAB9A, RAB11B, STX11A and VAMP7. In particular, increased RAB27A, RAB9A, RAB11B and STX11A expression was favorable for 3-year survival, while increased VAMP7 expression was unfavorable for 5-year survival (p¼0.008, p¼0.015, p¼0.011, p¼0.011 and p¼0.022, respectively). Conclusions:The results of this study suggest that biogenesis of the exosomes is deregulated in CRC. More studies are required to further explore its role in CRC progression and metastasis development.Legal entity responsible for the study: The authors.

gene expression and oncogenic pathways. The developments in microarray and nextgeneration sequencing platforms enabled the genome-scale identification of molecular dysregulations at the level of mRNA and the possible genomics-guided stratification of tumors for eventual targeted therapeutics. Numerous whole-genome profiles decoding the landscape of molecular determinants of gastric tumors have been established from Japan, South Korea, and China. However, such larger profiles of gastric tumors are largely lacking from India. This is the first comprehensive genomewide expression landscape covering mRNA, miRNA, lncRNA, and splice variants from India.Methods: Gastric tumor samples were collected from our hospital in both liquid nitrogen and RNA later. Quality analysis was performed in Agilent Bioanalyzer 2100 using RNA 6000 Nano chips. Genome-wide expression profiling covering mRNA, miRNA, alternate splicing and lncRNA was performed using Affymetrix HTA 2.0 arrays. The dysregulated genes were compared with the profiles established from other countries. Integrative genomic analysis revealed the transcription factors OCT, NFkB, NFAT, STAT, LEF, AP, PAX, SP1, ELK1, NFYA to be up-regulated and HNF, GATA to be down-regulated in tumors. The tumour samples were then subtyped into eight different groups based on the differential activation of 21 oncogenic signaling pathways. The clinical features, intraoperative details and histopathological characteristics of the samples of the patients were collected. Patients were then followed up for a period of 2 years for recurrence and DFS was calculated. Correlation between genomic subtypes of the tumour samples and clinical outcomes/recurrence patterns were analysed.Results: 108 patients who underwent distal gastrectomy were included in the study and genome-wide expression profiling were performed with their tumour samples. Based on the differential activation of 21 oncogenic signaling pathways, gastric cancer in this South Indian cohort could be subdivided into eight different subtypes. Among the eight subtypes, the subtype GC-1 that showed activation of differentiation-related pathways (Notch, NFAT, SP1-D, RXRA, ECM, HIF1A) was the most prevalent (n¼36). The subgroup GC-7 that demonstrated no significant activation of any pathway had propensity for extranodal extension from lymph nodes when compared to the other types (p-value 0.17). Subgroup 5 and subgroup 7 had greater propensity for spread to regional lymph nodes (p-value 0.45 and 0.42, respectively). The patients belonging to subgroup 7 developed metastasis at an earlier date (p-value 0.08).

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