The Predictive Value of Neutrophil Extracellular Trap-Related Risk Score in Prognosis and Immune Microenvironment of Colorectal Cancer Patients.

Colorectal cancer (CRC) has brought great healthy burden for patients. Neutrophil extracellular traps (NETs) have been explored in several tumors, while it remains largely unclear in CRC. CRC-related data were downloaded from Cancer Genome Atlas and Gene Expression Omnibus databases. Then, a NET risk score was built after univariate Cox and LASSO Cox regression analysis. Prognostic value was evaluated via survival analysis, stratification analysis, and ROC analysis. The functional enrichment analysis was conducted basing on bulk and scRNA-seq data. The immune landscape difference was analyzed using CIBERSORT, XCell, and MCPcounter portals. NET risk score was built for CRC patients, basing on G0S2, HIST1H2BC, CRISPLD2, and IL17A. In TCGA-CRC and validation datasets, regardless of age or gender, high-risk CRC patients had significantly worse prognosis, besides higher NET risk score was mainly found in samples with MSI-H and advanced T, N, and M stages. Employing multiple databases, we noticed that M0 and M2 Macrophages infiltrated the most in high-risk CRC patients, besides M2 Macrophages and neutrophils showed positive correlation with NET risk score. A novel reliable prognostic NET risk score was developed for CRC patients, and high-risk patients had unfavorable prognosis with advanced disease status.

Retrospective analysis of safety and efficacy of enhanced recovery pathways in stage II-III colorectal cancer patients submitted to surgery and adjuvant therapy.

BACKGROUND: The American Society of Colon and Rectal Surgeons is suggesting laparoscopic surgeries for colorectal cancer. Conventional perioperative procedures like long preoperative fasting and bowel procedures are not useful and harmful to patients undergoing surgeries for colorectal cancer. The objectives of the study were to compare surgery outcomes, hospital stays, and survival of patients who received fast-track (laparoscopy/open) surgical procedure followed by chemotherapy against those who received conventional (laparoscopy/open) surgical procedure followed by chemotherapy for colorectal cancer. METHODS: The study analyzes the outcomes of a total of 542 colorectal cancer (preoperative biopsies stage II or III) patients submitted to surgery and adjuvant chemotherapy. The study cohort is retrospectively subdivided in 4 groups submitted to open or laparoscopic resection with or without fast-track protocol appliance and two different chemotherapy regimens. Patients who ended up being TNM stage I have not received the adjuvant chemotherapy. RESULTS: The fast-track surgical procedure had shorter total hospital stays and postoperative hospital stays than the conventional surgical procedures. Flatus resumption time, the time until first defecation, and intraoperative blood loss were shorter for the fast-track surgical procedures than the conventional surgical procedures. Those surgery outcomes were also shorter for the fast-track laparoscopy than the open fast-track. Resumption of a fluid diet and ambulation onset time were shorter for the fast-track surgical procedures than the conventional surgical procedures. The surgical checkpoints that were compliance by patient of fast-track surgeries were significantly fewer than those of the conventional surgeries. Clinically significant difference for QLQ-C30/CR38 score after chemotherapy was reported between patients who received open conventional surgeries and those patients who received fast-track laparoscopy (59.63 ± 2.26 score/patient vs. 71.67 ± 5.19 score/patient). There were no significant differences for the number of patients with any grade adverse effects (p = 0.431) or with grade 3-4 adverse effects (p = 0.858), and the disease-free and overall survival among cohorts. CONCLUSIONS: The fast-track surgical procedure is effective and safe even in a multidisciplinary scenario as colorectal cancer treatment in which surgery is only a part of management. LEVEL OF EVIDENCE: III: Technical efficacy stage: 4.

STIM1 overexpression in hypoxia microenvironment contributes to pancreatic carcinoma progression.

OBJECTIVE: Stromal interaction molecule 1 (STIM1) overexpression has been reported to play an important role in progression of several cancers. However, the mechanism of STIM1 overexpression and its relationship with hypoxia in pancreatic ductal adenocarcinoma (PDAC) remains unclear. METHODS: STIM1 and HIF-1α expression was tested using immunohistochemistry in tissue microarray (TMA) including pancreatic cancer and matched normal pancreatic tissues, and their relationships with clinicopathological parameters were statistically analyzed. q-PCR, Western blot, ChIP, and luciferase assay were employed to 030 analyze transcriptional regulation between HIF-1α and STIM1 in pancreatic cancer PANC-1 cells. RESULTS: Both STIM1 and HIF-1α showed higher positive rates and up-regulated expression in cancer tissues compared to that of normal tissues (P < 0.05). The Kaplan-Meier method revealed that higher HIF-1α and STIM1 expression levels were significantly correlated with decreased disease-free survival ( P = 0.025 and P = 0.029, respectively). The expression of HIF-1α showed a significant positive correlation with that of STIM1 in cancer tissues (rs = 0.3343, P = 0.0011) and pancreatic cancer cell lines. Furthermore, ChIP and luciferase assays confirmed that HIF-1α bound to the STIM1 promoter and regulated its expression in PANC-1 cells. CONCLUSIONS: In hypoxia microenvironment, up-regulated expression of STIM1 mediated by HIF-1α promotes PDAC progression. HIF-1α and STIM1 are potential prognostic markers and/or therapeutic targets for PDAC treatment.