Search

Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. Long non-coding RNAs (lncRNAs) have been increasingly reported to serve vital parts in malignancies including CRC. Although cancer susceptibility 21 (CASC21) has been uncovered to play a part in CRC, its mechanism still needs further explanation. Thus, our study aimed to further explore the influence and mechanism of CASC21 in CRC progression. Quantitative real-time RT-PCR and western blot were performed to detect gene expression; a series of functional assays were performed to investigate the effect of CASC21 on CRC cells; in vivo tumour growth was evaluated via the nude mice xenograft model. The results revealed that CASC21 facilitated CRC cell proliferation, migration, epithelial-mesenchymal transition (EMT) and stemness. In addition, CASC21 was co-expressed with and bound to transcription factor POU5F1B (POU class 5 homeobox 1B). CASC21 recruited POU5F1B to HGH1 promoter to activate the transcription of HGH1 homolog. Also, CASC21 served as a competitive endogenous RNA (ceRNA) to up-regulate HGH1 via endogenously sponging miR-485-5p. Moreover, HGH1 overexpression counteracted the suppression of CASC21 deficiency on CRC tumour growth. In summary, our study indicated that CASC21 enhanced the expression of HGH1 to promote the malignancy of CRC by recruiting POU5F1B and sponging miR-485-5p, suggesting a key role of CASC21 in CRC progression. [ABSTRACT FROM AUTHOR]

Colorectal cancer is the third most prevalent cancer type worldwide and contributes to a significant percentage of cancer-related mortality. Recent studies have shown that the CXCR5 + CD8 + T cells present more potent proinflammatory function than CXCR5 − CD8 + T cells in chronic virus infections and in follicular lymphoma, but the role of CXCR5 + CD8 + T cells in colorectal cancer is yet unclear. In this study, we demonstrated that CXCR5 + CD8 + T cells were very rare in peripheral blood mononuclear cells from healthy and colorectal cancer individuals, but were significantly enriched in resected tumors and tumor-associated lymph nodes. Compared to CXCR5 − CD8 + T cells, the CXCR5 + CD8 + T cells demonstrated significantly higher Bcl-6 expression and lower Blimp1 expression, suggesting that CXCR5 + CD8 + T cells might represent a memory CD8 + T cell subset. CXCR5 + CD8 + T cells also enhanced the IgG expression by autologous B cells. Under ex vivo condition, the CXCR5 + CD8 + T cells demonstrated lower degranulation, TNFα expression and IFNγ expression than CXCR5 − CD8 + T cells. However, after PMA + ionomycin stimulation, the degranulation and TNFα expression by CXCR5 + CD8 + T cells were significantly elevated to a level comparable with CXCR5 − CD8 + T cells, whereas the IFNγ expression by PMA + ionomycin-stimulated CXCR5 + CD8 + T cells were significantly higher than that by CXCR5 − CD8 + T cells. Following long-term TCR-stimulation, CXCR5 + CD8 + T cells demonstrated significantly more potent proliferation capacity and higher IFNγ expression than CXCR5 − CD8 + T cells. TCR-stimulated CXCR5 + CD8 + T cells also showed a gradual downregulation in CXCR5 expression. We further found that TCR-stimulated CXCR5 + CD8 + T cells demonstrated higher granzyme B production and induced more specific lysis of autologous tumor cells than CXCR5 − CD8 + T cells. Together, these data demonstrate that CXCR5 + CD8 + T cells represent a significant CD8 + T cell subset in colorectal tumors and have the potential to contribute to antitumor immunity, but their specific roles require further studies in vivo. [ABSTRACT FROM AUTHOR]

Ubiquitin-specific peptidase 37 (USP37) is a novel deubiquitinating enzyme, which has been found to be involved in the progression of multiple tumors. However, its function in colorectal cancer (CRC) remains unclear. Here, we firstly proved that USP37 was up-regulated in CRC cases, and high USP37 expression predicted poor survival of CRC cases. USP37 up-regulation promoted the proliferation, cell cycle progression, apoptosis inhibition, migration, invasion, epithelial mesenchymal transition (EMT) and stemness of CRC cells; moreover, USP37 facilitated the angiogenesis of human umbilical vein endothelial cells (HUVECs). However, USP37 silencing showed the opposite function. In vivo experiment suggested that USP37 silencing suppressed the growth and lung metastasis of CRC in nude mice. Interestingly, we found that CTNNB1 (gene coding for β-catenin) level was positively correlated with USP37 level in CRC and USP37 silencing suppressed the expression of β-catenin in CRC cells and xenograft tumor tissues. Further mechanistic studies showed that USP37 could enhance the stability of β-catenin by inhibiting its ubiquitination. Taken together, USP37 acts as an oncogene in CRC, which promotes angiogenesis, metastasis and stemness by enhancing β-catenin stability via inhibiting its ubiquitination. USP37 may be a usefully target in CRC clinical treatment., Competing Interests: None., (AJCR Copyright © 2023.)

An increasing number of studies have revealed the role of long non-coding RNAs in cancer. However, the mechanisms of action and functional utility in colorectal cancer (CRC) have not been fully elucidated. Here we describe the functional role and potential mechanism of TINCR (terminal differentiation-induced non-coding RNA) in CRC. Firstly, TINCR was selected using sequencing analyses and the starBase database. Cell Counting Kit-8, scratch wound healing, and transwell assays revealed that TINCR inhibited proliferation and migration in SW620 and HTC116 cells. Intriguingly, TINCR expression was up-regulated in a radioresistant CRC cell line (SW620R). Although TINCR had no significant effects on SW620R cell proliferation or migration, knockdown of TINCR reduced the radioresistance, and its overexpression had opposite effects. We then focused on transcription factor 4 (TCF4) as it is downregulated in CRC and associated with increased stemness in tumors. We found that TINCR and TCF4 levels were positively related in SW620R cells. TINCR knockdown reduced sphere formation ability in SW620R cells. TINCR also suppressed the OCT4 and SOX2 stemness genes, despite having no effect on NANOG. The expression levels of these genes were substantially higher in SW620R than in SW620 cells. To further explore the mechanism of TINCR and radioresistance, miR-137 was analyzed as it targets TCF4. We firstly confirmed that TCF4 is a target of miR-137. We then identified that TINCR knockdown enhanced miR-137 expression in SW620R cells. Collectively, these findings suggest that TINCR knockdown inhibits TCF4 by regulating miR-137 expression., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Objective: To investigate the surgical efficacy and prognostic factors of T3NxM0 middle-low rectal cancer without neoadjuvant therapy., Methods: Clinical data of patients with middle-low rectal cancer undergoing TME surgery with T3NxM0 confirmed by postoperative pathology at Colorectal Surgery Department of Changhai Hospital from January 2008 to December 2010 were analyzed retrospectively., Inclusion Criteria: (1)no preoperative neoadjuvant chemoradiotherapy (nCRT); (2) complete preoperative evaluation, including medical history, preoperative colonoscopy or digital examination, blood tumor marker examination, and imaging examination; (3) distance between tumor lower margin and anal verge was ≤ 10 cm; (4) negative circumferential resection margin (CRM-). Finally, a total of 331 patients were included in this study. According to the number of metastatic lymph node confirmed by postoperative pathology, the patients were divided into N0 group without regional lymph node metastasis (190 cases) and N+ group with regional lymph node metastasis (141 cases). The perioperative conditions, local recurrence, distant metastasis and prognostic factors were analyzed., Results: Compared to N0 group in the perioperative data, N+ group had higher ratio of tumor deposit [29.8%(42/141) vs. 0, χ²=64.821, P<0.001] and vascular invasion [7.1%(10/141) vs. 0.5%(1/190),χ²=10.860, P<0.001]. There were no significant differences in tumor diameter, number of lymph nodes detected, positive nerve invasion, degree of tumor differentiation, morbidity of postoperative complication and postoperative adjuvant chemotherapy rate between the two groups (all P>0.05). The median follow-up period was 73.4 months. The merged 5-year local recurrence rate was 2.7%(9/331), 5-year distant metastasis rate was 23.3% (77/331), 5-year disease-free survival (DFS) rate was 73.4%, and 5-year overall survival (OS) rate was 77.2%. Multivariate analysis showed that lymph node metastasis (HR=3.120, 95%CI: 1.918 to 5.075, P<0.001), nerve invasion (HR=0.345, 95%CI: 0.156 to 0.760, P=0.008) and vascular invasion (HR=0.428, 95%CI: 0.189 to 0.972, P=0.043) were independent risk factors for DFS in patients with T3NxM0 rectal cancer after operation. Preoperative carcinoembryonic antigen level (HR=1.858, 95%CI:1.121 to 3.079, P=0.016), lymph node metastasis (HR=3.320, 95%CI: 1.985 to 5.553, P<0.001) and nerve invasion (HR=0.339, 95%CI: 0.156 to 0.738, P=0.006) were independent risk factors for OS in patients with T3NxM0 rectal cancer after operation., Conclusions: Optimal local control rate of middle-low rectal cancer patients with T3NxM0 and CRM- can be achieved by standard TME surgery alone. For patients with preoperative elevated blood carcinoembryonic antigen level, regional lymph node metastasis, or neurovascular invasion confirmed by pathology after surgery, adjuvant chemoradiotherapy should be actively applied after surgery to improve prognosis.

Objective: To summarize the diagnosis and treatment of iatrogenic colonoscopic perforation (ICP)., Methods: Clinical data, treatment course and outcome of 17 patients who developed ICP following colonoscopic examination or operation at Department of Colorectal Surgery, Changhai Hospital from January 2000 to December 2013 were retrospectively analyzed., Results: During above 13 years, a total of 127 106 patients underwent colonoscopic examination or operation, of whom 17 cases (0.013%) had ICP. There were 8 males and 9 females with an average age of 65.2 (32-85) years. The interval between the onset of ICP and clinically diagnosed ICP was 0 to 6 days after performance. ICP occurred in 8 patients following colonoscopy operations, including simple colonic polyp excision, endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD), while in 9 patients following simple colonoscopy examination. Except for one patient who was immediately diagnosed with ICP through the finding of "yellow adipose tissue visible in the vision field" during operation,7 early cases (41.2%) were diagnosed by abdominal X-ray examination, and 9 later cases were confirmed by abdominal CT examination. The perforation sites included sigmoid colon in 5 cases, caecum in 3 cases, descending colon in 3 cases, descending and sigmoid junction in 2 cases, ileum in 1 case, splenic flexure in 1 case, sigmoid and rectum junction in 1 case, retum in 1 case. One case with ICP following ESD after resection of polyp in caecum was cured successfully with conservative treatment, including fasting, gastrointestinal decompression, fluid infusion, anti-infection and nutritional support. One case with ICP, which was found during colonoscopic operation and the perforation was immediately closed with titanium clip, received conservative treatment, including anti-infection and then was cured. Fifteen patients underwent surgery, including 8 patients with primary intention intestinal perforation repair, 4 patients with primary intention resection of associated intestine and anastomosis, 2 patients with primary intention resection of associated intestine and ostomy, 1 patient with primary intention intestinal perforation repair and ostomy. Postoperative abdominal incision infection occurred in 4 cases, pulmonary infection in 1 case, incision infection with cardiovascular event or urinary tract infection in 1 case each. All the patients were cured and discharged. Average hospital stay was 18.6(3-45) days., Conclusions: ICP should be diagnosed by physical examination and imaging examination as soon as possible. For perforation during colonoscopic performance, colonoscopic titanium clip can be used for closure. Perforation repair is still the main procedure for ICP. If necessary, partial intestinal resection and anastomosis or ostomy can be selected.

Objective: To compare the surgical safety and short-term efficacy of minilaparotomy and laparoscopic approach for curative resection of rectal cancer., Methods: The retrospective cohort study was adopted. A review of patients scheduled to undergo a curative resection of rectal cancer via minilaparotomy or laparoscopic approach at Department of Colorectal Surgery of Changhai Hospital from June 2016 to May 2017 was carried out. All the patients were confirmed as rectal cancer by postoperative pathology. The following patients were excluded from the study: patients who had acute complete obstruction or perforation; patients underwent Miles or Hartmann procedure; patients who required an elongation of the skin incision in minilaparotomy or a conversion from laparoscopic to open surgery. Finally, 216 patients were enrolled in this study, of whom 143 were performed with minilaparotomy approach (minilaparotomy group) and 73 with laparoscopic approach (laparoscopic group) for curative resection of rectal cancer. For the minilaparotomy technique, a 7 cm longitudinal midline incision was made between the pubic symphysis and umbilicus; a wound retractor was applied to the edge of the wound; lymph node dissection around the inferior mesenteric and artery high ligation of inferior mesenteric artery were performed; by moving the minilaparotomy wound laterally and caudad or cephalad with the S-shaped hook, cautious mobilization of the relevant segment of the bowel loop was performed; bowel anastomosis was achieved by using the double-stapled technique; the gap of the pelvic floor peritoneum and mesentery were routinely closed by the absorbable surgical suture in cases with middle and low position rectal cancer. The surgical safety, the condition of resuming and the morbidity of postoperative complication were compared between the two groups., Results: There were 145 men and 71 women. Age ranged from 26 to 87 years, with of mean age of 61 years. According to the TNM stage grouping, there were 61 patients with stage I(, 62 with stage II(, 85 with stage III(, and 8 with stage IIII( disease, respectively. These two groups did not differ significantly in terms of age, sex, body mass index, site of tumor, TNM stage(all P>0.05). All the patients completed the operation successfully. The median operation time of minilaparotomy group was significantly shorter than that of laparoscopic group [164(80-296) minutes vs. 230(90-665) minutes, Z=4.410, P=0.000]. The intraoperative medical consumable expense [11000(7000-22000) yuan vs. 23000(12000-47000) yuan, Z=11.759, P=0.000] and the total hospitalization expense [44000(22000-146000) yuan vs. 57000(45000-126000) yuan, Z=9.637, P=0.000] were significantly lower in the minilaparotomy group. There were no significant differences between the two groups in terms of operative blood loss, number of harvested lymph nodes, distance of distal resection margin, positive rate of circumferential resection margin (all P>0.05). The rate of postoperative complication in minilaparotomy group was 7.0%(10/143) and in laparoscopic group was 9.6%(7/73) without significant difference (χ 2 =0.449, P=0.503). There were 2 patients in each group who required readmission to the hospital within postoperative 30 days. The cause of readmission was ileus or acute hyponatremia in minilaparotomy group, and ileus or pevic infection in laparoscopic group. One patient died of brain death caused by acute pulmonary embolism during the perioperative period in minilaparotomy group., Conclusions: The minilaparotomy approach for curative resection of rectal cancer is safe and feasible. As compared with laparoscopic approach, it is advantageous to achieve minimal invasiveness and early recovery, but much cheaper and less time consuming.

Objective: To investigate the relationship between tumor regression grade (TRG) and lymph node regression grade (LRG) after neoadjuvant chemoradiotherapy (CRT) for rectal cancer and its clinical implication., Methods: Clinicopathological data of 176 rectal cancer patients undergoing radical excision after neoadjuvant CRT from January 2005 to December 2013 in our department were retrospectively analyzed., Inclusion Criteria: (1) Radiology indicated locally advanced low rectal cancer and patients had strong desire to preserve the sphincter before neoadjuvant CRT; (2) there was no definite metastatic lesion before neoadjuvant CRT; (3) patients received whole course of neoadjuvant CRT (regular radiotherapy plus synchronous fluorouracil-like drugs chemotherapy); (4) patients underwent radical operation after neoadjuvant CRT. Patients with short-course CRT and emergency surgery were excluded. TRG and LRG of postoperative specimens (including tumor and lymph nodes) were carried out based on the percentage of the fibrosis and the cancer residue. No cancer residue was defined as TRG1 and LRG1; rare cancer cell residue as TRG2 and LRG2; fibrosis growth over residual cancer as TRG3 and LRG3; residual cancer growth over fibrosis as TRG4 and LRG4; absence of regressive changes as TRG5 and LRG5; and normal lymph nodes as LRG0. Spearman correlation test was used to assess the correlation between TRG and LRG., Results: Of 176 patients, 111 were men and 65 were women. The mean age was (53.9±13.0) years. The number of patients with stage I(, II(, and III( before operation was 10, 49 and 62 while other 55 patients were unknown. Transabdominal low anterior resection (LAR) was performed in 118 cases and abdominal-perineal resection(APR) in 47 cases following the principle of total mesorectal excision (TME). Postoperative pathology of specimens revealed that the number of patients from TRG1 to TRG5 was 19 (10.8%), 25 (14.2%), 66 (37.5%), 47 (26.7%), 19 (10.8%), and from LRG0 to LRG5 was 35 (19.9%), 68 (38.6%), 10 (5.7%), 14 (8.0%), 15(8.5%), 34 (19.3%), respectively. TRG was correlated to LRG (P=0.005) while the Spearman correlation coefficient was only 0.24. The analysis of subgroup without LRG1 also showed that TRG was correlated to LRG(P=0.0005) and the Spearman correlation coefficient was 0.40., Conclusions: TRG can not represent LRG. Therefore, both TRG and LRG should be assessed when evaluating the response of rectal cancer to neoadjuvant CRT.