Xin Jin

Abstract Most deaths from cancer are explained by metastasis, and yet large-scale metastasis research has been impractical owing to the complexity of in vivo models. Here we introduce an in vivo barcoding strategy that is capable of determining the metastatic potential of human cancer cell lines in mouse xenografts at scale. We validated the robustness, scalability and reproducibility of the method and applied it to 500 cell lines 1,2 spanning 21 types of solid tumour. We created a first-generation metastasis map (MetMap) that reveals organ-specific patterns of metastasis, enabling these patterns to be associated with clinical and genomic features. We demonstrate the utility of MetMap by investigating the molecular basis of breast cancers capable of metastasizing to the brain—a principal cause of death in patients with this type of cancer. Breast cancers capable of metastasizing to the brain showed evidence of altered lipid metabolism. Perturbation of lipid metabolism in these cells curbed brain metastasis development, suggesting a therapeutic strategy to combat the disease and demonstrating the utility of MetMap as a resource to support metastasis research.

Abstract The effective treatment of advanced cervical cancer remains challenging. Herein, single‐nucleus RNA sequencing (snRNA‐seq) and SpaTial enhanced resolution omics‐sequencing (Stereo‐seq) are used to investigate the immunological microenvironment of cervical squamous cell carcinoma (CSCC). The expression levels of most immune suppressive genes in the tumor and inflammation areas of CSCC are not significantly higher than those in the non‐cancer samples, except for LGALS9 and IDO1 . Stronger signals of CD56 + NK cells and immature dendritic cells are found in the hypermetabolic tumor areas, whereas more eosinophils, immature B cells, and Treg cells are found in the hypometabolic tumor areas. Moreover, a cluster of pro‐tumorigenic cancer‐associated myofibroblasts (myCAFs) are identified. The myCAFs may support the growth and metastasis of tumors by inhibiting lymphocyte infiltration and remodeling of the tumor extracellular matrix. Furthermore, these myCAFs are associated with poorer survival probability in patients with CSCC, predict resistance to immunotherapy, and might be present in a small fraction (< 30%) of patients with advanced cancer. Immunohistochemistry and multiplex immunofluorescence staining are conducted to validate the spatial distribution and potential function of myCAFs. Collectively, these findings enhance the understanding of the immunological microenvironment of CSCC and shed light on the treatment of advanced CSCC.

BACKGROUND: Small nucleolar RNA host gene 12 (SNHG12) has been shown to be a long noncoding RNA (lncRNA) that facilitates the progression of a number of malignancies. However, the expression pattern and biological function of SNHG12 in nasopharyngeal carcinoma (NPC) have not been investigated. OBJECTIVE: The aim of our study is to investigate the expression, clinical significance and function of SNHG12 in NPC. METHODS: RT-PCR was used to detect the expression of SNHG12 in NPC cell lines and primary tumor tissues. The correlation of SNHG12 with clinicopathological features and patient prognosis was analyzed. The biologic functions of SNHG12 in NPC were explored by MTT assay, colony formation assay, wound healing assays, transwell assay and flow cytometric analysis in vitro. The expression of EMT markers and Notch signal pathway markers were determined by western blotting. RESULTS: The expression levels of SNHG12 were up-regulated in both NPC tissues and cell lines. High SNHG12 expression was significantly associated with clinical stage, grade and poor prognosis. Multivariate analysis demonstrated that high lncRNA SNHG12 expression was an independent poor prognostic factor for NPC patients. Functionally, knockdown of SNHG12 suppressed NPC cells proliferation, migration and invasion. Mechanistic investigations showed that knockdown of SNHG12 suppressed the activation of EMT and Notch-1 signal pathway. CONCLUSIONS: Our data suggest that SNHG12 promotes the progression of NPC and is a potential therapeutic target for NPC intervention.