Tumor cells of colorectal cancer (CRC) release exosomes into the circulation. These exosomes can mediate communication between cells and affect various tumor‐related processes in their target cells. We present a quantitative proteomics analysis of the exosomes purified from serum of patients with CRC and normal volunteers; data are available via ProteomeXchange with identifier PXD003875. We identified 918 proteins with an overlap of 725 Gene IDs in the Exocarta proteins list. Compared with the serum‐purified exosomes (SPEs) of normal volunteers, we found 36 proteins upregulated and 22 proteins downregulated in the SPEs of CRC patients. Bioinformatics analysis revealed that upregulated proteins are involved in processes that modulate the pretumorigenic microenvironment for metastasis. In contrast, differentially expressed proteins (DEPs) that play critical roles in tumor growth and cell survival were principally downregulated. Our study demonstrates that SPEs of CRC patients play a pivotal role in promoting the tumor invasiveness, but have minimal influence on putative alterations in tumor survival or proliferation. According to bioinformatics analysis, we speculate that the protein contents of exosomes might be associated with whether they are involved in premetastatic niche establishment or growth and survival of metastatic tumor cells. This information will be helpful in elucidating the pathophysiological functions of tumor‐derived exosomes, and aid in the development of CRC diagnostics and therapeutics.

Recently, the distinction between left- and right-sided colon cancer (LCC and RCC) has been brought into focus. RCC is associated with an inferior overall survival and progression-free survival. We aimed to perform a detailed analysis of the diversity of extracellular vesicles (EV) between LCC and RCC using quantitative proteomics and to identify for new diagnostic and prognostic biomarkers. We isolated EVs from patients with LCC, RCC and healthy volunteers, and treated colorectal cancer cell line with serum-derived EVs. We then performed a quantitative proteomics analysis of the serum-derived EVs and cell line treated with EVs. Proteomic data are available via ProteomeXchange with the identifiers PXD012283 and PXD012304. In addition, we assessed the performance of EV SPARC and LRG1 as diagnosis and prognosis biomarkers in colon cancer. The expression profile of the serum EV proteome in patients with RCC was different from that of patients with LCC. Serum-derived EVs in RCC promoted cellular mobility more significantly than EVs derived from LCC. EV SPARC and LRG1 expression levels demonstrated area under the receiver-operating characteristic curve values of 0.95 and 0.93 for discriminating patients with colon cancer from healthy controls. Moreover, the expression levels of SPARC and LRG1 correlated with tumour sidedness and were predictive of tumour recurrence. We identified differences in EV protein profiles between LCC and RCC. Serum-derived EVs of RCC may promote metastasis via upregulation of extracellular matrix (ECM)-related proteins, especially SPARC and LRG1, which may serve as diagnosis and prognosis biomarkers in colon cancer.

The extent of lymphadenectomy during laparoscopic right colectomy can affect the oncological outcome and the safety of surgery. The principle of complete mesocolic excision (CME) has been gradually accepted and increasingly applied by colorectal surgeons. The aim of this study is to investigate whether extended lymphadenectomy (CME) in laparoscopic colectomy could improve the oncological outcomes of patients with right-sided colon cancers, compared with D2 lymphadenectomy. The Radical Extent of lympadenectomy: D2 dissection versus complete mesocolic excision of LAparoscopic Right Colectomy for right-sided colon cancer (RELARC) study is a prospective, multicenter, randomized controlled trial in which 1072 eligible patients with right-sided colon cancers will be randomly assigned to the CME group or the D2 dissection group during laparoscopic right colectomy. Inclusion criteria are locally advanced colon cancers situated from the cecum to the right third of the transverse colon and clinically staged as T2-4aN0M0 or TanyN + M0. The primary endpoint of this trial is 3-year disease-free survival. Secondary endpoints include 3-year overall survival, postoperative complication rates, perioperative mortality rates, and rates of positive central lymph nodes (the station 3 nodes). The RELARC trial is a prospective, multicenter, randomized controlled trial that will provide evidence on the optimal extent of lymphadenectomy during laparoscopic right colectomy in terms of better oncological outcome and operation safety. ClinicalTrials.gov: NCT02619942 . Registered on 29 November 2015.

It is becoming increasingly clear that cancers can rarely be ascribed to just one or a few genomic variations. Genes generally do not function alone, but in groups that function as “networks”. This study aimed to develop a competing endogenous RNA (ceRNA) network to elucidate the role of long non-coding RNA H19 in colorectal cancer. Large-scale RNA-seq data was obtained from The Cancer Genome Atlas database. Differentially expressed RNAs were identified by bioinformatics analysis, and a competing endogenous RNA network was constructed. Functional enrichment analysis and correlation analysis between competing endogenous RNAs and clinical features were performed to reveal their roles in the tumorigenesis of colorectal cancer. To verify the conclusions derived from bioinformatics analysis, we investigated the effect of lncRNA H19 knockdown in human colorectal cancer cell lines HT-29 and HCT116. The present study successfully identify various cancer-specific lncRNAs and pseudogenes in CRC. The lncRNA/pseudogene–miRNA–mRNA ceRNA network was constructed using 10 lncRNAs, 5 pseudogenes, 122 mRNAs and 39 miRNAs. In the ceRNA network of CRC, H19 up-regulates various cancer-related mRNA by competitively sponging various miRNA, and participates in PI3K–Akt signaling pathway in this manner. Cox regression and correlation analysis showed that H19 and some other competing endogenous RNAs in the network are associated with poor prognosis and clinical parameters such as tumor grade and metastasis. Knockdown of H19 reduces the protein level of MET, ZEB1, and COL1A1 in vitro. H19 regulates PI3K–Akt signal pathway through a competing endogenous RNA network and predicts poor prognosis in colorectal cancer. The pseudogene RPLP0P2 may be an important oncogene like H19 and needs to be studied further.

Magnetic resonance imaging-based artificial intelligence model in rectal cancer

The existing in vitro models for antitumor drug screening have significant limitations. Many compounds that inhibit two-dimensional (2D) cultured cells do not exhibit the same pharmacological effects in vivo, thereby wasting human and material resources and time during drug development. Therefore, it is crucial to develop new models. Three-dimensional (3D) bioprinting technology has greater advantages in constructing human tissues than sandwich culture and organoid construction. We used 3D bioprinting technology to construct a 3D multicellular model of SW480 cells, tumor-associated macrophages, and endothelial cells. The biological activities of the model were evaluated by immunofluorescence, hematoxylin and eosin staining of frozen pathological sections, and transcriptome sequencing. Compared with 3D bioprinted single-cell model (3D printing-S), 3D bioprinted multicellular models (3D printing-M) showed significantly improved expression of tumor-related genes, including hub genes IL1B, FCGR2A, FCGR3A, CYBB, SPI1, CCL2, ITGAM, and ITGB2. Antitumor drug screening experiment showed that the IC50 values of 5-FU, oxaliplatin, and irinotecan in 3D printing-S group/2D culture group were 31.13 µM/12.79 µM, 26.79 µM/0.80 µM, and 16.73 µM/10.45 µM, respectively. Compared with the 3D printing-S group, 3D printing-M group was significantly more resistant to chemotherapy.