Upregulation of CRABP2 by TET1-mediated DNA hydroxymethylation attenuates mitochondrial apoptosis and promotes oxaliplatin resistance in gastric cancer.

Oxaliplatin is the main chemotherapy drug for gastric cancer (GC), but quite a few patients are resistant to oxaliplatin, which contributes to the poor prognosis of GC patients. There is therefore an urgent need to identify potential targets for reversing chemotherapy resistance in GC patients. In this study, we analyzed the tumor samples of GC patients who received neoadjuvant chemotherapy based on oxaliplatin through quantitative proteomics and identified the potential chemoresistance-related protein cellular retinoic acid binding protein 2 (CRABP2). CRABP2 was significantly upregulated in the tumor tissues of chemoresistant GC patients and was closely related to prognosis. The results of cell function experiments showed that CRABP2 can promote the oxaliplatin resistance of GC cells in vitro. Coimmunoprecipitation and GST pulldown assays showed that CRAPB2 expedited the binding of BAX and PARKIN in GC cells and facilitated the ubiquitination-mediated degradation of BAX. Furthermore, both the in vitro assay and cell-derived xenograft (CDX) in vivo model verified that CRABP2 promoted oxaliplatin resistance by inhibiting BAX-dependent cell apoptosis. Further experiments proved that the abnormally high expression of CRABP2 in oxaliplatin-resistant GC cells was affected by TET1-mediated DNA hydroxymethylation. The patient-derived xenograft (PDX) model suggested that interference with CRABP2 reversed oxaliplatin resistance in GC in vivo. In conclusion, the results of our study show that CRABP2 was a key molecule in oxaliplatin resistance regulation and could be a new target for reversing the chemoresistance of GC.

Comparison of reverse puncture device and overlap in laparoscopic total gastrectomy for gastric cancer.

BACKGROUND: Intracorporeal oesophagojejunostomy is one of the key steps in laparoscopic total gastrectomy (LTG). At present, there is no widely accepted anastomosis technique in oesophagojejunostomy. MATERIALS AND METHODS: We retrospectively studied 63 patients with gastric cancer who underwent LTG. Two types of anastomosis techniques have been applied during LTG: the reverse puncture device (RPD) (28 patients) and overlap (35 patients). RESULTS: A total of 63 patients (51 males and 12 females: mean age = 58 years and mean body mass index [BMI] = 26.3 kg/m2) were enrolled in this study. There were no significant difference in age, BMI, duration of surgery, duration of anastomosis, blood loss, post-operative hospital stay, tumour location, tumour size, degree of tumour differentiation, Borrmann type, total number of lymph nodes, number of positive lymph nodes, hospital stay, hospitalisation costs, intra-operative complications, post-operative complications and prognosis between the RPD group and the overlap group. RPD group showed a significant advantage in terms of the distance between the top border of tumours and the top resection margin (P < 0.001). We further found that the oesophageal lateral negative surgical margin distance of the upper gastric cancer in the RPD group was significantly longer than that in the overlap group (P < 0.001). CONCLUSIONS: Both the RPD and overlap techniques are safe and applicable in LTG. However, RPD has the advantage of obtaining an adequate safe margin compared with that of overlap technique, especially in patients with gastro-oesophageal junction carcinoma.

Randomized Controlled Trial Comparing the Short-term Outcomes of Enhanced Recovery After Surgery and Conventional Care in Laparoscopic Distal Gastrectomy (GISSG1901).

OBJECTIVE: This study aimed to compare the effects of ERAS and conventional programs on short-term outcomes after LDG. SUMMARY OF BACKGROUND DATA: Currently, the ERAS program is broadly applied in surgical areas. Although several benefits of LDG with the ERAS program have been covered, high-level evidence is still limited, specifically in advanced gastric cancer. METHODS: The present study was designed as a randomized, multicenter, unblinded trial. The enrollment criteria included histologically confirmed cT2-4aN0-3M0 gastric adenocarcinoma. Postoperative complications, mortality, readmission, medical costs, recovery, and laboratory outcomes were compared between the ERAS and conventional groups. RESULTS: Between April 2019 and May 2020, 400 consecutive patients who met the enrollment criteria were enrolled. They were randomly allocated to either the ERAS group (n = 200) or the conventional group (n = 200). After excluding patients who did not undergo surgery or gastrectomy, 370 patients were analyzed. The patient demographic characteristics were not different between the 2 groups. The conventional group had a significantly longer allowed day of discharge and postoperative hospital stay (6.96 vs 5.83 days, P < 0.001; 8.85 vs 7.27 days, P < 0.001); a longer time to first flatus, liquid intake and ambulation (3.37 vs 2.52 days, P < 0.001; 3.09 vs 1.13 days, P < 0.001; 2.85 vs 1.38 days, P < 0.001, respectively); and higher medical costs (6826 vs 6328 $, P = 0.027) than the ERAS group. Additionally, patients in the ERAS group were more likely to initiate adjuvant chemotherapy earlier (29 vs 32 days, P = 0.035). There was no significant difference in postoperative complications or in the mortality or readmission rates. Regarding laboratory outcomes, the procalcitonin and C-reactive protein levels on postoperative day 3 were significantly lower and the hemoglobin levels on postoperative day 5 were significantly higher in the ERAS group than in the conventional group. CONCLUSION: The ERAS program provides a faster recovery, a shorter postoperative hospitalization length, and lower medical costs after LDG without increasing complication and readmission rates. Moreover, enhanced recovery in the ERAS group enables early initiation of adjuvant chemotherapy.

Effect of preoperative CT angiography examination on the clinical outcome of patients with BMI ≥ 25.0 kg/m2 undergoing laparoscopic gastrectomy: study protocol for a multicentre randomized controlled trial.

BACKGROUND: Gastric cancer, which is the fifth most common malignancy and the third most common cause of cancer-related death, is particularly predominant in East Asian countries, such as China, Japan and Korea. It is a serious global health issue that causes a heavy financial burden for the government and family. To our knowledge, there are few reports of multicentre randomized controlled trials on the utilization of CT angiography (CTA) for patients who are histologically diagnosed with gastric cancer before surgery. Therefore, we planned this RCT to verify whether the utilization of CTA can change the short- and long-term clinical outcomes. METHOD: The GISSG 20-01 study is a multicentre, prospective, open-label clinical study that emphasises the application of CTA for patients who will undergo laparoscopic gastrectomy to prove its clinical findings. A total of 382 patients who meet the inclusion criteria will be recruited for the study and randomly divided into two groups in a 1:1 ratio: the CTA group (n = 191) and the non-CTA group (n = 191). Both groups will undergo upper abdomen enhanced CT, and the CTA group will also receive CT angiography. The primary endpoint of this trial is the volume of blood loss. The second primary endpoints are the number of retrieved lymph nodes, postoperative recovery course, hospitalization costs, length of hospitalization days, postoperative complications, 3-year OS and 3-year DFS. DISCUSSION: It is anticipated that the results of this trial will provide high-level evidence and have clinical value for the application of CTA in laparoscopic gastrectomy. TRIAL REGISTRATION: ClinicalTrials.gov , NCT04636099. Registered November 19, 2020.

UBQLN4 is activated by C/EBPß and exerts oncogenic effects on colorectal cancer via the Wnt/ß-catenin signaling pathway.

Ubiquilin 4 (UBQLN4) is an important member of the ubiquitin-like protein family. An increasing number of studies have shown that UBQLN4 is an important regulator of tumorigenesis. Nevertheless, the biological function and detailed mechanisms of UBQLN4 in colorectal cancer (CRC) development and progression remain unclear. Here, we identified UBQLN4 upregulation in CRC tissues and it is positively associated with CRC size, TNM stage, and lymphatic metastasis. Patients with high UBQLN4 expression had a poor prognosis. Functionally, overexpression of UBQLN4 significantly promoted CRC cell proliferation, migration, and invasion, while UBQLN4 silencing elicited the opposite effect. This result was consistent with the conclusion that UBQLN4 expression correlated positively with the CRC size and lymphatic metastasis. In vivo, UBQLN4 silencing also inhibited tumor growth. Mechanistically, using gene set enrichment analysis (GSEA) and western blot experiments, we identified that UBQLN4 activated the Wnt/ß-catenin signaling pathway to upregulate ß-catenin and c-Myc expression, thereby promoting CRC proliferation, migration and invasion. A rescue experiment further verified this conclusion. Dual luciferase reporter, real-time quantitative PCR (RT-qPCR), western blot and chromatin immunoprecipitation (ChIP) assays indicated that the transcription factor CCAAT/enhancer-binding protein beta (C/EBPß) directly bound to the UBQLN4 core promoter region and activated its transcription, upregulating ß-catenin and c-Myc expression to promote CRC progression. Thus, our findings suggest that UBQLN4 is a key oncogene in CRC and may be a promising target for the diagnosis and treatment of patients with CRC.

PRMT3 promotes tumorigenesis by methylating and stabilizing HIF1α in colorectal cancer.

Abnormal angiogenesis occurs during the growth of solid tumors resulting in increased vascular permeability to fluids and metastatic cancer cells. Anti-angiogenesis therapy for solid tumors is effective in the treatment of cancer patients. However, the efficacy of anti-angiogenesis therapy is limited by drug resistance. The findings of the current study showed that HIF1α R282 is methylated by PRMT3, which is necessary for its stabilization and oncogene function. Analysis showed that PRMT3-mediated tumorigenesis is HIF1α methylation-dependent. A novel therapeutic molecule (MPG-peptide) was used to inhibit HIF1α expression. These findings provided information on PRMT3 signaling pathway and HIF1/VEGFA signaling pathway and offer a novel therapeutic strategy for colorectal cancer, mainly for treatment of anti-angiogenesis resistance patients.

Association of Abdominal Incision Length With Gastrointestinal Function Recovery Post-operatively: A Multicenter Registry System-Based Retrospective Cohort Study.

Objective: To evaluate the influence of the abdominal incision length on the gastrointestinal function recovery post-operatively. Background: Gut motility recovers more quickly after the minimally invasive laparoscopic surgery compared than after the traditional open surgery; however, whether the minimal abdominal incision contributes to the faster gut motility recovery is controversial and lacks solid clinical evidence. Methods: A registry-based secondary cohort analysis was conducted to evaluate the association between the abdominal incision length and gut motility recovery post-operatively based on a multicenter, prospective, and observational study of the prolonged post-operative ileus (PPOI) incidence and the risk factors in the patients with the major abdominal surgery. The incision length, in the centimeters, was the exposure. The primary outcome measures were the PPOI incidence and its association with the incision length. The secondary outcome included the days to the first passage of flatus and the days to the first passage of stool. Results: Overall, 1,840 patients, including 287 (15.7%) patients with the PPOI, were recruited. The PPOI incidence was 17.6% and 13.3% in the long-incision (>18 cm) and short-incision patients ( ≤ 18 cm), respectively. The incidence of the PPOI increased by 1.1% (1.0-1.1) by each centimeter increment of the incision length after adjusting for the confounding factors. In comparison to the short-incision patients, the long-incision patients had prolonged passage of stool (4.46 vs. 4.95 days, p < 0.001). Each centimeter increment of the incision length contributed to a 2% increased risk of delay in the first bowel movement [hazard ratio (HR) 0.980 (0.967, 0.994)]. Conclusion: A long abdominal incision length independently contributed to the prolonged gut function recovery post-operatively mainly by delaying the time to the first bowel movement, but not influencing the time to first passage of flatus.

Exosome-transmitted circCOG2 promotes colorectal cancer progression via miR-1305/TGF-ß2/SMAD3 pathway.

Circular RNAs (circRNA) are abundantly present in the exosome. Yet, the role of exosome-transmitted circRNA in colorectal cancer (CRC) remains unclear. In this study, we examined the function and mechanism of circCOG2 in CRC. We analyzed the expression of circCOG2 in CRC tissues, plasmas, and exosomes by qRT-PCR. The function of circCOG2 was evaluated by CCK-8, clone formation, transwell and wound healing assay, and using an in vivo study; while its mechanism was analyzed using a dual luciferase reporter assay, RNA pull-down assay, Western blot, and rescue experiments. We found that circCOG2 was increased in CRC tissues, plasmas, and exosomes. Upregulated circCOG2 promoted CRC proliferation, migration, and invasion through the miR-1305/TGF-ß2/SMAD3 pathway, and this effect could be transmitted from CRC cells with the high metastatic potential to CRC cells with low metastatic potential by exosomes. Our results revealed that circCOG2 is correlated with poor prognosis and may be used as a therapeutic target for CRC.

Prognostic Significance of Signet-Ring Cell Components in Patients With Gastric Carcinoma of Different Stages.

Background: Gastric carcinoma (GC), which contains signet ring cell (SRC) components are frequently observed in postoperative pathological assessment. This study aims to study the prognostic significance of SRC components in GC patients. Methods: From 2003 to 2017, surgically resected primary GC patients were retrospectively reviewed. All enrolled patients were divided into three groups according to the proportion of SRC. The overall survival (OS) and disease-free survival (DFS) of GC patients with different tumor stages were analyzed. Results: Patients with SRC or mixed-SRC were more associated with female, younger age, middle or lower third of the stomach, larger tumor, higher pN stage, and more lymphovascular invasion. For GC patients in stage I, multivariate survival analysis showed that age >60, SRC components >50%, and pT stage were independent prognostic factors for OS (all p < 0.05). The 5-year OS of patients with SRC were higher than that of patients with pure adenocarcinoma (p = 0.021). For GC patients in stage II/III, multivariate survival analysis showed that age >60, SRC proportion, surgical types, Borrmann's type, pT stage, pN stage, and lymphovascular invasion were independent prognostic factors for OS (all p < 0.05). The 5-year OS/DFS of patients with SRC were lower than that of patients with pure adenocarcinoma (p < 0.001). Conclusions: SRC seemed to be a favorable prognostic factor in GC patients in stage I. However, for GC patients in stage II/III, the SRC components were associated with poor prognosis, independent of other clinicopathological factors.

Preservation of the left colic artery and superior rectal artery in laparoscopic surgery can reduce anastomotic leakage in sigmoid colon cancer.

BACKGROUND: The aim was to study the clinical significance in the preservation of the left colic artery (LCA) and superior rectal artery (SRA) for the laparoscopic resection of sigmoid colon cancer (SCC). PATIENTS AND METHODS: A total of 316 patients with SCC were divided into two groups. Group A received D3 resection with preservation of LCA and SRA, whereas Group B ligatured artery at the root of the inferior mesenteric artery. The operation time, number of resected lymph nodes, blood loss and anastomotic leakage rate were compared. RESULTS: In Group A, the average operation time was 283.02 ± 51.48 min, the average blood loss was 111.81 ± 77.08 ml and the average lymph node dissection was 14.8 ± 7.7. There was no statistical significance in blood loss and number of resected lymph nodes between Group A and B (P > 0.05). Longer operating time were observed in Group A as compared to Group B (P < 0.05). The anastomotic leakage rate had statistical significance between these two groups (P < 0.05). CONCLUSIONS: Preservation of LCA and SRA was safe and feasible for the laparoscopic surgery of SCC, which could reduce anastomotic leakage rate.

Histological Differentiated/Undifferentiated Mixed Type Should Not Be Considered as a Non-Curative Factor of Endoscopic Resection for Patients With Early Gastric Cancer.

BACKGROUND: Histological differentiated/undifferentiated mixed-type adenocarcinomas are frequently found in patients with early gastric cancer (EGC). Yet it is unclear whether these mixed-type adenocarcinomas can be treated by endoscopic resection (ER) in EGC patients. AIMS: To evaluate the lymph node metastasis (LNM) rate and long-term outcomes in mixed-type EGC patients and assess the feasibility of ER in these patients. METHODS: Clinicopathological features, risk factors of LNM, and overall survival (OS) and progression-free survival (PFS) rates of EGC patients were analyzed according to different histological types. RESULTS: Patients with mixed-type EGC had higher LNM rates than patients with non-mixed-type EGC (11.4 vs. 6.2%, P = 0.044). In the multivariate analysis, larger tumor diameter, presence of an ulcer, submucosal invasion, histological undifferentiated type, histological mixed type, and lymphovascular invasion resulted as independent risk factors for LNM in EGC patients (all P < 0.05). The LNM rate in mixed-type patients who met the Japanese ER criteria was 3.3%, including fulfilling the absolute criteria 0%. The 5-year OS and PFS rates in mixed-type patients were 94.59 and 91.47%, respectively. There was no statistical significance in the OS (P = 0.870) and PFS (P = 0.705) between mixed-type and non-mixed-type EGC patients fulfilling the Japanese ER criteria. CONCLUSION: Histological differentiated/undifferentiated mixed type in EGC patients meeting the Japanese absolute criteria for ER are associated with low risk of LNM and favorable prognosis, and thus, it should not be considered as a non-curative factor for ER.

Hsa_circ_0026416 promotes proliferation and migration in colorectal cancer via miR-346/NFIB axis.

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers worldwide. Circular RNAs (circRNAs), a novel class of non-coding RNAs, have been confirmed to be key regulators of many diseases. With many scholars devoted to studying the biological function and mechanism of circRNAs, their mysterious veil is gradually being revealed. In our research, we explored a new circRNA, hsa_circ_0026416, which was identified as upregulated in CRC with the largest fold change (logFC = 3.70) of the evaluated circRNAs via analysing expression profiling data by high throughput sequencing of members of the GEO dataset (GSE77661) to explore the molecular mechanisms of CRC. METHODS: qRT-PCR and western blot analysis were utilized to assess the expression of hsa_circ_0026416, miR-346 and Nuclear Factor I/B (NFIB). CCK-8 and transwell assays were utilized to examine cell proliferation, migration and invasion in vitro, respectively. A luciferase reporter assay was used to verify the combination of hsa_circ_0026416, miR-346 and NFIB. A nude mouse xenograft model was also utilized to determine the role of hsa_circ_0026416 in CRC cell growth in vivo. RESULTS: Hsa_circ_0026416 was markedly upregulated in CRC patient tissues and plasma and was a poor prognosis in CRC patients. In addition, the area under the curve (AUC) of hsa_circ_0026416 (0.767) was greater than the AUC of CEA (0.670), CA19-9 (0.592) and CA72-4 (0.575). Functionally, hsa_circ_0026416 promotes cell proliferation, migration and invasion both in vitro and in vivo. Mechanistically, hsa_circ_0026416 may function as a ceRNA via competitively absorbing miR-346 to upregulate the expression of NFIB. CONCLUSIONS: In summary, our findings demonstrate that hsa_circ_0026416 is an oncogene in CRC. Hsa_circ_0026416 promotes the progression of CRC via the miR-346/NFIB axis and may represent a potential biomarker for diagnosis and therapy in CRC.

Primary gastric squamous cell carcinoma presenting as a large submucosal mass: A case report and literature review.

RATIONALE: Primary gastric squamous cell carcinoma (SCC) is rarely encountered clinically. SCC, which presents as a submucosal tumor, is even rarer. Without the support of pathological evidence, it is difficult to make a correct preoperative diagnosis. Due to limited clinical data, the pathogenesis and treatment of gastric SCC remain unclear. PATIENT CONCERNS: A 69-year-old man was admitted to our hospital with unexplained weight loss. Endoscopy revealed a submucosal mass without any ulcer on its surface located on the body of the stomach. The results of 2 gastroscopic mucosal biopsies were chronic inflammation. DIAGNOSES: The clinical diagnosis by computed tomography (CT) and gastroscopy was gastrointestinal stromal tumor (GIST) preoperatively. The postoperative pathological examination demonstrated this tumor as moderately differentiated SCC. INTERVENTIONS: Total gastrectomy, distal pancreatectomy, and splenectomy were performed. OUTCOMES: The patient was discharged 7 days after the surgery without any complications. The follow-up CT scan showed no evidence of metastatic disease 6 months after surgery. LESSONS: Large primary gastric SCC could present as a submucosal mass. Gastroscopic mucosal biopsy may not be able to get tumor tissue due to inflammatory reaction.

Circular noncoding RNA circMBOAT2 is a novel tumor marker and regulates proliferation/migration by sponging miR-519d-3p in colorectal cancer.

Colorectal cancer (CRC) is a common malignant tumor with a poor prognosis. However, its pathogenesis has not been fully elucidated, accounting for poor overall survival. Circular RNA (circRNA) is a class of noncoding RNAs discovered many years ago. Only recently have they been re-evaluated for their important roles in the regulation of gene expression. Studies have confirmed that circRNAs have important biological functions in a variety of malignant tumors. This study aimed to characterize one circRNA derived from the MBOAT2 gene and termed it circMBOAT2, which has been reported to promote prostate cancer progression. CircMBOAT2 is highly expressed in both CRC tissues and serum samples, and has a correlation with tumor stage. The receiver-operating characteristic curves suggested that circMBOAT2 acted as a novel diagnostic tumor marker in CRC. Univariate and multivariate analyses showed that the levels of circMBOAT2 in tissues were independent prognostic markers of CRC. Further functional studies revealed that circMBOAT2 served as a microRNA (miRNA) sponge of miR-519d-3p and promoted the proliferation, migration, and invasion of CRC cells. Also, circMBOAT2 regulated cell proliferation and migration by competitively binding to miR-519d-3p and targeting troponin-associated protein (TROAP) in CRC cells. These results suggested that circMBOAT2 might be a novel potential biomarker of CRC.

The histone deacetylase HDAC1 activates HIF1α/VEGFA signal pathway in colorectal cancer.

Tumor angiogenesis is a common feature of rapidly growing solid tumors, accelerated by tumor hypoxia. It is associated with subsequent metastasis, progression, poor prognosis, and aggressive phenotype in many types of cancer. The hypoxia-inducible factors/vascular endothelial growth factor 1(HIF1/VEGF) signal pathway plays an important role in tumor angiogenesis. Proteasome-mediated ubiquitin degradation pathway is one of the most important processes involved in regulating the level of cellular HIF-1α. Our study revealed that Histone Deacetylase 1 (HDAC1) directly inhibits the ubiquitination of HIF1α. Additionally, HDAC1 activates HIF1α/VEGFA signaling pathway, promoting s tumor angiogenesis. These findings have enhanced our understanding of the molecular mechanisms of colorectal (CRC) tumor angiogenesis. HDAC1/HIF1α/VEGFA signaling pathway may provide a novel therapeutic window for CRC.

Effects of perioperative enhanced recovery after surgery pathway management versus traditional management on the clinical outcomes of laparoscopic-assisted radical resection of distal gastric cancer: study protocol for a randomized controlled trial.

BACKGROUND: The incidence of gastric cancer in East Asia is much higher than the international average. Therefore, improving the prognosis of patients and establishing effective clinical pathways are important topics for the prevention and treatment of gastric cancer. At present, the enhanced recovery after surgery (ERAS) pathway is widely used in the field of gastric surgery. Many randomized controlled trial (RCT) studies have proven that the ERAS regimen can improve the short-term clinical outcomes of patients with gastric cancer. However, a prospective study on the effect of the ERAS pathway on the prognosis of patients with gastric cancer has not yet been reported. This trial aims to confirm whether the ERAS pathway can improve the disease-free survival and overall survival of patients undergoing laparoscopic-assisted radical resection for distal gastric cancer. METHODS/DESIGN: This study is a prospective, multicentre RCT. This experiment will consist of two groups - an experimental group and a control group - randomly divided in a 1:1 ratio. The perioperative period of the experimental group will be managed according to the ERAS pathway and that of the control group will be managed according to the traditional management mode. An estimated 400 patients will be enrolled. The main endpoint for comparison is the 3-year overall survival and disease-free survival between the two groups. DISCUSSION: The results of this RCT should clarify whether the ERAS pathway is superior to traditional treatment on inflammatory indexes, short-term clinical outcome and survival for laparoscopic-assisted radical resection of distal gastric cancer. It is hoped that our data will provide evidence that the ERAS pathway improves survival in patients with gastric cancer. TRIAL REGISTRATION: Chinese Clinical Trial Registry, CHiCTR1900022438. Registered on 11 April 2019.

Translation regulatory long non-coding RNA 1 represents a potential prognostic biomarker for colorectal cancer.

Long non-coding RNAs (lncRNAs) have attracted a lot of attention for their role in the development, progression and prognosis of colorectal cancer (CRC). However, little is known on the clinical significance of the translation regulatory lncRNA 1 (TRERNA1) in CRC. The present study aimed to explore the clinical value of TRERNA1 in patients with CRC. A total of 89 cancer-associated lncRNA genes were analyzed using the RT2 lncRNA PCR array Human Cancer PathwayFinder. Following the PCR array, reverse transcription-quantitative (RT-q)PCR was conducted to identify the differential expression of TRERNA1 between 130 CRC and corresponding non-tumorous adjacent tissues. Additionally, the association between TRERNA1 expression and clinical characteristics was analyzed. Furthermore, TRERNA1 expression was knocked down via small interfering RNAs. The results of the PCR array and RT-qPCR revealed that TRERNA1 expression was significantly upregulated in CRC tissues compared with in adjacent normal tissues. TRERNA1 upregulation was positively associated with distant metastasis, perineural invasion, TNM stage, node metastasis stage and tumor diameter. Multivariate analysis revealed that patients with higher TRERNA1 expression had a shorter overall survival (OS) time and a less favorable prognosis compared with those in the low TRERNA1 expression group. Knockdown of TRERNA1 inhibited invasion and metastasis of CRC cells via regulating Snail expression. In conclusion, TRERNA1 expression was upregulated in CRC tissues. High expression levels of TRERNA1 may be associated with poor OS times, a less favorable prognosis and lymph node metastasis in patients with CRC. TRERNA1 may therefore serve as a useful and novel biomarker for CRC lymph node metastasis and prognosis.

Total Tumor Volume Should be Considered as an Important Prognostic Factor for Synchronous Multiple Gastric Cancer Patients with Curative Gastrectomy.

Synchronous multiple gastric cancer (SMGC) was a special type of gastric cancer with relatively low incidence. This article was designed to demonstrate that the total tumor volume (TTV) should be treated as an important prognostic factor in SMGC patients with curative gastrectomy. This study retrospective analyzed 140 SMGC patients who received curative gastrectomy between December 2004 and December 2014 in our hospital. Clinicopathological features, preoperative evaluation, surgical treatment, and outcome parameters were reviewed and analyzed. This study applied univariate and multivariate analyses to identify the most significant prognostic factors. In the univariate analysis, the TTV, pTTVNM, pN stage, pT of main tumor were all significant prognostic factors in SMGC patients (all P < 0.05). In the multivariate analysis, pN stage, TTV and pTTVNM were confirmed to be independent prognostic factors (all P < 0.05). In the comparison of survival analysis, the pTTVNM stage system (P < 0.05) was superior to the pTNM stage system (P > 0.05) in SMGC patients. In conclusion, the TTV should be considered as an independent prognostic factor in overall survival in SMGC patients who received curative gastrectomy. The pTTVNM stage should be recommended as a suitable staging system for SMGC patients.

International consensus on natural orifice specimen extraction surgery (NOSES) for gastric cancer (2019).

At present, natural orifice specimen extraction surgery (NOSES) has attracted more and more attention worldwide, because of its great advantages including minimal cutaneous trauma and post-operative pain, fast post-operative recovery, short hospital stay, and positive psychological impact. However, NOSES for the treatment of gastric cancer (GC) is still in its infancy, and there is great potential to improve its theoretical system and clinical practice. Especially, several key points including oncological outcomes, bacteriological concerns, indication selection, and standardized surgical procedures are raised with this innovative technique. Therefore, it is necessary to achieve an international consensus to regulate the implementation of GC-NOSES, which is of great significance for healthy and orderly development of NOSES worldwide.