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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.amjsurg.2009.05.005 Byline: Zhanlong Shen, Yingjiang Ye, Liang Bin, Mujun Yin, Xiaodong Yang, Kewei Jiang, Shan Wang Keywords: Metabolic syndrome; Colorectal cancer; Recurrence; Survival; Liver metastases; Body mass index; Obesity Abstract: Several studies have shown that metabolic syndrome (MS) was a risk factor for colorectal cancer, but few studies have reported the relationship between MS and the prognosis of colorectal cancer. Author Affiliation: Department of Gastroenterological Surgery, Peking University, People's Hospital, Beijing 100044, People's Republic of China Article History: Received 10 August 2008; Revised 7 May 2009 Article Note: (footnote) The authors have no conflicts of interest.

ABSTRACTAccumulating evidence has demonstrated that N6-methyladenosine (m6A) plays important roles in various cancers, making it essential to profile m6A modifications at a transcriptome-wide scale in colorectal cancer (CRC). In the present study, we performed high-throughput sequencing to determine the m6A methylome in CRC. We obtained six pairs of CRC samples and tumour-adjacent normal tissues from Peking University People’s Hospital. We used MeRIP-seq to determine that compared to the tumour-adjacent normal tissues, the CRC samples had 1343 dysregulated m6A peaks, and 625 m6A peaks were significantly upregulated and 718 m6A peaks were significantly downregulated. Genes with altered m6A peaks play critical roles in regulating glucose metabolism, RNA metabolism, and cancer stem cells. Furthermore, we identified 297 hypermethylated m6A peaks and 328 hypomethylated m6A peaks in mRNAs through conjoint analyses of MeRIP-seq and RNA-seq data. After analysing these genes with differentially methylated m6A peaks and synchronously differential expression, we identified four genes (WDR72, SPTBN2, MORC2, and PARM1) that were associated with prognosis of colorectal cancer patients by searching The Cancer Genome Atlas (TCGA). Our study suggests that m6A modifications play important roles in tumour progression and survival of CRC patients. The results also indicate that modulating m6A modifications may represent an alternative strategy to predict the survival of cancer patients and interfere with tumour progression in the future.

T cells are key elements of cancer immunotherapy1but certain fundamental properties, such as the development and migration of T cells within tumours, remain unknown. The enormous T cell receptor (TCR) repertoire, which is required for the recognition of foreign and self-antigens2, could serve as lineage tags to track these T cells in tumours3. Here we obtained transcriptomes of 11,138 single T cells from 12 patients with colorectal cancer, and developed single T cell analysis by RNA sequencing and TCR tracking (STARTRAC) indices to quantitatively analyse the dynamic relationships among 20 identified T cell subsets with distinct functions and clonalities. Although both CD8+effector and ‘exhausted’ T cells exhibited high clonal expansion, they were independently connected with tumour-resident CD8+effector memory cells, implicating a TCR-based fate decision. Of the CD4+T cells, most tumour-infiltrating T regulatory (Treg) cells showed clonal exclusivity, whereas certain Tregcell clones were developmentally linked to several T helper (TH) cell clones. Notably, we identified two IFNG+TH1-like cell clusters in tumours that were associated with distinct IFN?-regulating transcription factors —the GZMK+effector memory T cells, which were associated with EOMESand RUNX3, and CXCL13+BHLHE40+TH1-like cell clusters, which were associated with BHLHE40. Only CXCL13+BHLHE40+TH1-like cells were preferentially enriched in patients with microsatellite-instable tumours, and this might explain their favourable responses to immune-checkpoint blockade. Furthermore, IGFLR1was highly expressed in both CXCL13+BHLHE40+TH1-like cells and CD8+exhausted T cells and possessed co-stimulatory functions. Our integrated STARTRAC analyses provide a powerful approach to dissect the T cell properties in colorectal cancer comprehensively, and could provide insights into the dynamic relationships of T cells in other cancers.

•The prognosis of AFPP-GC was poor, with a high risk of liver metastasis.•The mechanism of AFPP-GC with high malignant potential might be due to the immunosuppressive microenvironment and more malignant tumor cells.•AFPP-GC may promote cell invasion by regulating the PTEN/AKT1/SOX5/CES1 signaling axis.

ABSTRACTIncreasing evidence has shown that abnormal expression of lncRNAs is involved in various biological behaviors and major cellular pathways of human cancers. However, the role of lncRNAs in the progression of gastric cancer has not been adequately investigated. Therefore, in this study, we investigated the expression levels of linc-GPR65-1 using Quantitative real-time PCR (qRT-PCR) and found that linc-GPR65-1 was significantly up-regulated in 50 gastric cancer tissues compared to the corresponding normal tissues. In addition, increased linc-GPR65-1 expression was associated with TNM stage (P = 0.037), tumor size (P = 0.024), distal metastasis (P = 0.023), and poor prognosis of gastric cancer patients. Moreover, functional assays indicated that decreased linc-GPR65-1 expression inhibited the aggressive phenotypes of gastric cancer cells, and enhanced linc-GPR65-1 expression resulted in the opposite phenomenon. Then, a cancer signaling phosphoantibody microarray was conducted to explore the potential mechanisms of linc-GPR65-1 in regulating gastric cancer progression and observed that linc-GPR65-1 could regulate the PTEN-AKT-slug signaling pathway. These data showed that linc-GPR65-1, regulating the PTEN-AKT-slug signaling pathway, might act as a tumor promoter and serve as a novel target for gastric cancer prevention and therapy.

ABSTRACTAccumulating evidence has suggested that circular RNAs (circRNAs) play important roles in oncogenesis and tumor progression. However, our knowledge of circRNAs in gastric cancer (GC) remains limited. To investigate circRNAs involved in GC oncogenesis, we examined differentially-expressed circRNAs and mRNAs in GC tissues and paired noncancerous mucosa tissues using circRNA and mRNA microarrays. Next, we built gene co-expression networks according to the degree of correlation to predict the critical circRNAs in GC. Through bioinformatics analysis, we observed three newly identified circRNAs that are substantially upregulated in GC: hsa_circ_0047905, hsa_circ_0138960 and has-circRNA7690-15. Additionally, hsa_circ_0047905 and hsa_circ_0138960 positively correlated with their parental gene mRNA. Knockdown of hsa_circ_0047905, hsa_circ_0138960 and has-circRNA7690-15 in GC cells, resulted in downregulation of parental gene expression. Functional assays suggested that inhibition of these three circular RNAs suppresses GC cell proliferation and invasion in vitro. Those findings suggest that hsa_circ_0047905, hsa_circ_0138960 and has-circRNA7690-15 might act as tumor promoters in the pathogenesis of gastric cancer.

Background: The tumor microenvironment (TME) has been shown to strongly influence treatment outcome for cancer patients in various indications and to influence the overall survival. However, the cells forming the TME in gastric cancer have not been extensively characterized. Results: We combine bulk and single-cell RNA sequencing from tumors and matched normal tissue of 24 treatment-naïve GC patients to better understand which cell types and transcriptional programs are associated with malignant transformation of the stomach. Clustering 96,623 cells of non-epithelial origin reveals 81 well-defined TME cell types. We find that activated fibroblasts and endothelial cells are most prominently overrepresented in tumors. Intercellular network reconstruction and survival analysis of an independent cohort imply the importance of these cell types together with immunosuppressive myeloid cell subsets and regulatory T cells in establishing an immunosuppressive microenvironment that correlates with worsened prognosis and lack of response in anti-PD1-treated patients. In contrast, we find a subset of IFNγ activated T cells and HLA-II expressing macrophages that are linked to treatment response and increased overall survival. Conclusions: Our gastric cancer single-cell TME compendium together with the matched bulk transcriptome data provides a unique resource for the identification of new potential biomarkers for patient stratification. This study helps further to elucidate the mechanism of gastric cancer and provides insights for therapy.

We aimed to compare the safety and oncological outcomes of transanal endoscopic microsurgery (TEM) and radical surgery (RS) for patients with T1 or T2 rectal cancer.