Disruption of the c-Myc/miR-200b-3p/PRDX2 regulatory loop enhances tumor metastasis and chemotherapeutic resistance in colorectal cancer.

BACKGROUND: Metastasis is a major threat to colorectal cancer (CRC) patients. We have reported that peroxiredoxin-2 (PRDX2) is associated with CRC invasion and metastasis. However, the mechanisms regulating PRDX2 expression remain unclear. We investigate whether microRNAs (miRNAs) regulate PRDX2 expression in CRC progression. METHODS: Quantitative real-time polymerase chain reaction (qPCR) was used to measure microRNA-200b-3p (miR-200b-3p) expression. Immunohistochemistry (IHC) was performed to detect c-Myc and PRDX2 protein levels in CRC tissue samples (n = 97). Western blot was used to quantify PRDX2, c-Myc, AKT2/GSK3ß pathway-associated proteins and epithelial-mesenchymal transition (EMT)-related proteins in CRC cells. Luciferase reporter assays were used to analyze the interaction between miR-200b-3p and 3'untranslated region (3'UTR) of PRDX2 mRNA and AKT2 mRNA as well as c-Myc and the miR-200b-3p promoter. Chromatin immunoprecipitation (ChIP) assay was used to evaluate binding of c-Myc to the miR-200b-3p promoter. Invasive assay and metastatic model were used to assess invasive and metastatic capacities of CRC cells in vitro and in vivo. Moreover, drug-induced apoptosis was measured by flow cytometry. RESULTS: We found that miR-200b-3p was significantly downregulated, whereas c-Myc and PRDX2 were upregulated in metastatic CRC cells and CRC tissues compared to their counterparts. An inverse correlation existed between c-Myc and miR-200b-3p, and between miR-200b-3p and PRDX2. We also found that PRDX2 was a target of miR-200b-3p. Importantly, overexpression of nontargetable PRDX2 eliminated the suppressive effects of miR-200b-3p on proliferation, invasion, EMT, chemotherapeutic resistance and metastasis of CRC cells. Moreover, c-Myc bound to the promoter of miR-200b-3p and repressed its transcription. In turn, miR-200b-3p disrupted the stability of c-Myc protein by inducing c-Myc protein threonine 58 (T58) phosphorylation and serine 62 (S62) dephosphorylation via AKT2/GSK3ß pathway. CONCLUSIONS: Our findings reveal that the c-Myc/miR-200b/PRDX2 loop regulates CRC progression and its disruption enhances tumor metastasis and chemotherapeutic resistance in CRC.

Risk Analysis of Positive PD-L1 Expression and Clinicopathological Features and Survival Prognosis in Patients with Colorectal Cancer: Systematic Review and Meta-Analysis.

In order to explore the significance of PD-L1 expression in the prognosis and clinicopathological characteristics of colorectal cancer (CRC), the PubMed, Embase, Web of Science, Cochrane Library, CNKI, and multisquare databases are systematically searched for the relevant relationship between PD-L1 expression and CRC prognosis. The search time is completed until June 2021. Literature is filtered and data extracted by inclusion exclusion criteria, and Meta-analysis is performed with Stata SE12.0 software. 16 documents are included, and a total of 1997 CRC patients are included. The results show that recurrence-free survival (RFS) [OR = 2.69, 95%CI (2.07,3.48), P < 0.00001, I2 = 0%, Z = 7.50), and disease-free survival (DFS) (OR = 3.71, 95% CI (2.32,5.93), P < 0.00001, I2 = 37%, Z = 5.48) and PD-L1 expression and tumor differentiation (OR = 4.00, 95%CI (2.97,5.38), P < 0.00001, I2 = 0%, Z = 9.11) and lymphatic action metastasis (OR = 2.69,95% CI (2.07,3.48), P < 0.00001, I2 = 0%, Z = 7.50) is significantly associated.PD-L1 expression in tumor tissue suggests a poor prognosis in colorectal cancer, and the predictive significance of PD-L1 expression and PD-L1 expression in tumor cells in tumor-infiltrating immune cells may be inconsistent.

Laparoscopic radical resection for situs inversus totalis with colonic splenic flexure carcinoma: A case report.

BACKGROUND: Situs inversus totalis (SIT) is a rare group of congenital developmental malformations in the clinical setting, with all organs in the chest and abdomen existing in a mirror image reversal of their normal positions. Few reports have described laparoscopic surgery for colorectal cancer in patients with SIT, and it is considered difficult even for an experienced surgeon because of the mirror positioning. We present a case report of laparoscopic radical resection of a colonic splenic flexure carcinoma in a patient with SIT. CASE SUMMARY: A 72-year-old male was referred to our hospital with colonic splenic flexure carcinoma, and computed tomography showed that all the organs in the chest and abdomen were inverted. Laparoscopic hemicolectomy with complete mesocolic excision was safely performed. The operating surgeon stood on the patient's left side, which is opposite of the normal location. CONCLUSION: Abdominal computed tomography is an effective method for diagnosing SIT preoperatively in patients with colonic splenic flexure carcinomas. Laparoscopic radical resection is difficult, but it is well established and safe. The surgeon should stand in the opposite position and perform backhand operations.

Transcecum catheterization ileostomy is safe and effective to prevent anastomotic leakage in post-laparoscopic rectal cancer surgery: a single-center retrospective study.

Background: Preventive ileostomy (PI) is conventionally performed to prevent anastomotic leakage (AL) after laparoscopic total mesorectal excision (LTME) for low rectal cancer; however, secondary surgery is required to remove the ostomy tube. We designed a new type of ostomy, transcecum catheterization ileostomy (TCI) to prevent AL. Its principle is similar to PI, but no secondary operation is needed. We evaluated the safety and efficacy of TCI in AL prevention. Methods: We analyzed the data of patients who underwent LTME with low anastomosis in Chongqing University Cancer Hospital from October 2015 to August 2021. Patients were divided into three groups according to their choice: those who underwent TCI (TCI group), those who underwent PI (PI group), and those who undergo none (C group). Intra-operation situation, postoperative efficacy and safety indicators were compared between three groups. Results: Out of the total 534 patients included, 171 underwent TCI, 156 underwent PI, and 207 underwent none. No statistically difference was noted in baseline characteristics between three groups (all P>0.05). Operation time was longer in TCI group and PI group than in C group (P<0.001). No difference was noted in intraoperative blood loss or the number of lymph nodes dissected (P=0.685 and P=0.153). Moreover, no difference was noted in the serum levels of immune cells on postoperative day 1, 3, and 7 (all P>0.05) or in the levels of serum C-reactive protein (CRP), procalcitonin (PCT), and interleukin 6 (IL-6; all P>0.05). No difference was noted in postoperative incision, pulmonary infection rates and intestinal obstruction incidence (P=0.530, P=0.971, and P=0.938). AL incidence and AL-related reoperation rates were lower in TCI or PI group (P=0.002 and P<0.001). The rate of anastomotic stricture was lower in TCI group than in the other two groups (P<0.001). Conclusions: TCI is effective to prevent AL when performed during LTME. But TCI cannot completely avoid AL. When AL occurs, TCI can reduce the degree of abdominal infection and the secondary surgical rate related AL. TCI presents an alternative option to PI, that does not require secondary operation. Therefore, TCI is safe and worthy of application.

Peroxiredoxin 2 is associated with colorectal cancer progression and poor survival of patients.

The present study was to investigate the clinical significance of peroxiredoxin 2 (PRDX2), an oncoenzyme, in the development and progression of colorectal cancer(CRC).We found levels of PRDX2 mRNA and protein were higher in CRC cell lines than in normal human colonic epithelial cells. PRDX2 expression was significantly up-regulated in CRC lesions compared with that in the adjacent noncancerous tissues. CRC tissues from 148 of 226 (65.5%) patients revealed high level of PRDX2 protein expression in contrast to only 13 of 226 (5.8%) PRDX2 strong staining cases in the adjacent noncancerous tissues. Increased expression of PRDX2 protein was significantly associated with poor tumor differentiation (p = 0.001), advanced local invasion (p = 0.046), increased lymph node metastasis (p = 0.008), and advanced TNM stage (p = 0.020). Patients with higher PRDX2 expression had a significantly shorter disease-free survival and worse disease-specific survival than those with low expression. Importantly, PRDX2 up-regulation was an independent prognostic indicator for stage I-III, early stage (stage I-II) and advanced stage (stage III) patients. In conclusion, our findings suggest PRDX2 up-regulation correlates with tumor progression and could serve as a useful marker for the prognosis of CRC.