Alsaihati, B. | Search bioRxiv

bioRxiv2020

Metastasis and cancer stem cell markers identify two colorectal cancer subtypes with different molecular and clinical features

Colorectal cancer (CRC) is among the top prevalent cancer types with lethal outcome in the United States and worldwide. CRC inter-tumor heterogeneity highlights the importance of identifying molecular markers for meaningful classification and prognosis. The recently published Consensus Molecular Subtypes (CMS) represent a widely used molecular subtyping system of CRC. However, our analyses indicate that clear heterogeneity still exists in some CMSs. In this work, we demonstrate that both CMS2 and CMS4 are composed of two molecularly distinct subtypes. We named them S1 and S2, short for subtype 1 and subtype 2. Our results indicate that the two subtypes also differ clinically. Notably, S2 exhibits more frequent lymphatic invasion across CRCs and more frequent metastasis events within CMS2 patients.

bioinformatics↗

bioRxiv2018

The interplay of immune components and ECM in oral cancer

We report that in Oral Squamous Cell Carcinoma (OSCC), extracellular matrix (ECM) plays a vitally important role in defining the characteristics of cancer vs. normal, as it is a compartment with significant enrichment of known OSCC biomarkers, and the number of genes constituting ECM are more prominently upregulated in OSCC than almost all the rest of the cancer types. This is probably due to the constant exposure of oral cavity to external stimuli, resulting in the ECM remodeling, which further is a key player in tumor invasion. While we showed ECM molecules alone could well distinguish oral cancer from normal tissue samples, a significant portion of these predictive ECM molecules, share the same transcriptional regulator, NFKB1, a master regulator of immune response. We further studied the level of involvement of the immune system in OSCC, and found that the immune composition in OSCC is distinctly different from the other cancer types. OSCC has a higher level of infiltration of adaptive immune cells, including B cell, T cell and neutrophil, compared with other cancer types, while a lower level of infiltration of innate immune, including macrophage and monocyte. Previous studies have revealed the roles of ECM and immune system in OSCC development, and our study showed that ECM plays a very prominent role in OSCC, subject to the complex microenvironment in oral cavity, particularly the immune system profile, and our association analysis revealed it is likely the interactions between ECM and immune cells that define the highly invasive property of OSCC.

bioinformatics↗