The characteristics and clinical relevance of tumor fusion burden in non-EBV (+) gastric cancer with MSS.

BACKGROUND: Next-generation sequencing (NGS) is maturely applied for gene fusion detection. Although tumor fusion burden (TFB) has been identified as an immune marker for cancer, the relationship between these fusions and the immunogenicity and molecular characteristics of gastric cancer (GC) patients remains unclear. GCs have different clinical significance depending on their subtypes, and thus, this study aimed to investigate the characteristics and clinical relevance of TFB in non-Epstein-Barr-virus-positive (EBV+) GC with microsatellite stability (MSS). METHODS: A total of 319 GC patients from The Cancer Genome Atlas stomach adenocarcinoma (TCGA-STAD) and a cohort of 45-case from ENA (PRJEB25780) were included. The cohort characteristics and distribution of TFB among the patients were analyzed. Additionally, the correlations of TFB with mutation characteristics, pathway differences, relative abundance of immune cells, and prognosis were examined in the TCGA-STAD cohort of MSS and non-EBV (+) patients. RESULTS: We observed that in the MSS and non-EBV (+) cohort, the TFB-low group exhibited significantly lower gene mutation frequency, gene copy number, loss of heterozygosity score, and tumor mutation burden than in the TFB-high group. Additionally, the TFB-low group exhibited a higher abundance of immune cells. Furthermore, the immune gene signatures were significantly upregulated in the TFB-low group, 2-year disease-specific survival was markedly increased in the TFB-low group compared with to the TFB-high group. The rates of TFB-low cases were significantly higher TFB-than high cases in durable clinical benefit (DCB) and response groups with pembrolizumab treatment. Low TFB may serve as a predictor of GC prognosis, and the TFB-low group exhibits higher immunogenicity. CONCLUSION: In conclusion, this study reveals that the TFB-based classification of GC patient may be instructive for individualized immunotherapy regimens.

LINC01133 hampers the development of gastric cancer through increasing somatostatin via binding to microRNA-576-5p.

Aim: Our study aimed at investigating how LINC01133 functions in gastric cancer (GC) progression. Materials & methods: Gain-of-function and loss-of-function approaches were applied to analyze the effects of LINC01133, microRNA-576-5p (miR-576-5p) and somatostatin (SST) on the biological behaviors of GC cells and in tumor-bearing nude mice. Results: GC tissues and cells showed low expression of LINC01133, and LINC01133 overexpression decreased malignant phenotypes of GC cells. Moreover, LINC01133 upregulated SST through binding to miR-576-5p. Overexpressing miR-576-5p or suppressing SST reversed the functions of LINC01133 in biological potentials of GC cells and tumor growth. Conclusion: LINC01133 overexpression may inhibit GC development by downregulation of miR-576-5p and upregulation of SST, which suggests new therapeutic targets for GC.

Long noncoding RNA TPT1-AS1 promotes the progression and metastasis of colorectal cancer by upregulating the TPT1-mediated FAK and JAK-STAT3 signalling pathways.

Tumour protein translationally controlled 1 (TPT1) antisense RNA 1 (TPT1-AS1) is known to be involved in the development and metastasis of cervical and ovarian cancers; however, its biological role in colorectal cancer (CRC) remains unknown. This study aimed to determine the function and mechanism of action of TPT1-AS1 in the progression and metastasis of CRC. Elevated TPT1-AS1 levels were observed in CRC tissues. Furthermore, the high expression levels were found to be correlated with unfavourable clinicopathological characteristics in CRC. Cell function experiments demonstrated that TPT1-AS1 depletion impeded cell proliferation, migration and invasion and enhanced cell adhesion; it also attenuated tumorigenesis and metastasis in vivo. Additionally, TPT1-AS1 was predominately located in the nuclei of the cells and could upregulate the expression of TPT1 by recruiting mixed lineage leukaemia protein-1 (MLL1), which increased the trimethylation of H3K4 me3 in the TPT1 promoter region and subsequently activated FAK and JAK-STAT3 signalling cascades. The inhibition of FAK activation by PF573228 significantly attenuated the oncogenic effect of TPT1-AS1. These findings indicated that TPT1-AS1 promoted tumour progression and metastasis in CRC by upregulating TPT1 levels and activating the FAK and JAK-STAT3 signalling pathways. Thus, TPT1-AS1 may be considered as a potential therapeutic target for CRC.

Analysis of Clinical Efficiency and Safety of Laparoscopic Anus-Conserving Operation for Ultralow Rectal Cancer.

To explore the efficiency and safety of laparoscopic anus-conserving operation for ultralow rectal cancer, we retrospectively reviewed 236 patients with ultralow rectal cancer who underwent laparoscopic anus-conserving operation (experimental group, n = 124) or conventional open surgery (control group, n = 112). Operation-related indexes, pathological results of mesentery, incidence rates of postoperative complications, anus preservation rates, anal sphincter controllability after surgery, and survival rates of the first, second, and third years after operation were compared between the two groups. The amount of intraoperative bleeding, first postoperative exhaust time, abdominal drainage, pain score, and hospital stay in the experimental group were significantly less than those in the control group (P < 0.05). There were no significant differences in the postoperative circumferential resection margin, distal resection margin, number of dissected lymph nodes, successful resection rate, and quality of mesorectum between the two groups (P > 0.05). The total incidence rate of postoperative complications, anal sphincter controllability, and survival rates after surgery were similar between the two groups (P > 0.05). The anus preservation rate of the experimental group (84.7%) was significantly higher than that of the control group (69.6%) (P < 0.05). Laparoscopic anus-conserving operation is effective and safe in treatment of patients with ultralow rectal cancer, which has advantages such as small trauma, less intraoperative bleeding, short hospital stay, rapid recovery, a low incidence rate of postoperative complications, and a high anus-preserving rate, so it is worthy of clinical application.

Portable detection of colorectal cancer SW620 cells by using a personal glucose meter.

It is of great value to develop general, low-cost and even household methods for colorectal cancer detection. Here, a portable detection strategy based on a personal glucose meter (PGM) was designed for meeting this purpose. In this strategy, the anti-EpCAM coated magnet beads (MBs) were used as capture probes for enriching cancer cells and the aptamer modified and invertase loaded graphene oxides (GO) were used as report probes for producing glucose signal. This method is sensitive with detection limit as low as 560 cells, and demonstrates excellent detection specificity. Meanwhile, we succeeded in the specific detection of target cells in 20% human serum samples, indicating this method has great prospect in clinical diagnosis. Moreover, this method presents favourable universality for detecting different colorectal cancer cells by just using different recognition aptamers. Importantly, this method can be implemented for the target cell detection at room temperature without any expensive and large-scale instruments but a portable PGM. Therefore, this portable detection method possesses great potential in point-of-care detection of colorectal cancer cells.

Long noncoding AFAP1-antisense RNA 1 is upregulated and promotes tumorigenesis in gastric cancer.

Long noncoding RNA serves important roles in gastric cancer (GC). However, the prognostic significance and tumorigenesis effect of AFAP1-antisense RNA 1 (AS1) in GC remain to be clarified. The present study was conducted in order to determine the expression level of AFAP1-AS1 by reverse transcription-quantitative polymerase chain reaction. It was demonstrated that AFAP1-AS1 expression level was higher in GC tissues in comparison with adjacent tissues. By analyzing 66 GC tissue specimens, AFAP1-AS1 expression level was found to be markedly associated with tumor size, clinical stage and differentiation. By performing multivariate Cox regression test, AFAP1-AS1 expression level was confirmed to be an independent factor for poor prognosis in patients with GC. Furthermore, SGC-7901 and BGC-823 cells were used for further investigation following transfection of an AFAP1-AS1 short hairpin RNA lentiviral vector. Knockdown of AFAP1-AS1 significantly inhibited GC cell proliferation, migration and invasion abilities in vitro. Finally, nude mice experiments confirmed that downregulation of AFAP1-AS1 in GC cells suppressed tumor growth in vivo. In conclusion, the results of the present study suggested that AFAP1-AS1 may serve as a valuable prognostic indicator and therapeutic target for GC.

Effectiveness and safety of total laparoscopic distal gastrectomy versus laparoscopy-assisted distal gastrectomy for gastric cancer: A retrospective cohort study.

AIM: To compare the results of total laparoscopic distal gastrectomy (TLDG) and laparoscopy-assisted distal gastrectomy (LADG) and explore the safety and feasibility of TLDG. METHODS: Data were collected and analyzed from patients underwent TLDG and LADG from January 2009 to December 2011 at our institution. RESULTS: 127 LADG cases and 104 TLDG cases were included and balanced for age, sex, BMI, ASA scores, and CEA level in this study. A decrease in postoperative pain (P < 0.001), wound infection rate (P = 0.013), and hospitalization time after surgery (P < 0.001) was found in the TLDG group. Compared with the LADG group, there was no increase in operative time (P = 0.084), intraoperative blood loss (P = 0.061), or anastomotic fistula rate (P = 0.473). Statistical differences did not exist in recurrence and (or) metastasis (P = 0.204), 5-years disease-free survival (DFS) rate and overall survival (OS) (P = 0.570 and 0.560, respectively). CONCLUSION: As long as it follows the surgical principles of malignant tumor, TLDG can achieve the same therapeutic effect as LADG does. TLDG is safe and feasible for gastric cancer patients though further studies are needed.

Identification of HnRNP M as a novel biomarker for colorectal carcinoma by quantitative proteomics.

Colorectal carcinoma (CRC) is one of the most common cancers in the world, and identification of new CRC biomarkers will be helpful for the diagnosis and treatment of CRC. For isobaric tags for relative and absolute quantitation (iTRAQ) analysis, fresh CRC and adjacent, colonic adenoma, ulcerative colitis, Crohn's disease, and noncancerous colonic epithelial tissue were obtained from patients at the 2nd Xiangya Hospital of Central South University, China. The function of heterogeneous nuclear ribonucleoprotein M (HnRNP M) during the proliferation, invasion, and metastasis of CRC cells in vitro was evaluated. One hundred and twenty-six differentially expressed proteins were identified by iTRAQ analysis. The expression of HnRNP M exhibited progressive changes during the carcinogenic process and was validated by Western blot. The upregulation of HnRNP M correlated with cancer recurrence and regional lymph node metastasis. Furthermore, biological role exploration suggests that HnRNP M positively regulates cell cycle progression, promotes cell growth and invasion in vitro, and increases the colony-forming ability of LS174T cells. The present data demonstrate that the upregulation of HnRNP M is involved in human colorectal epithelial carcinogenesis and may serve as a carcinoma biomarker for CRC.

[Laparoscopic partial gastrectomy: Analysis of 18 procedures].

OBJECTIVE: To explore the laparoscopic partial gastrectomy and the indications. METHODS: Eighteen patients who underwent laparoscopic partial gastrectomy from August 2005 to May 2006 were analyzed retrospectively. RESULTS: Sixteen patients (including 6 with gastric cancer, 9 with duodenal ulcer, and 1 with gastric multiple polyps) underwent laparoscopic partial gastrectomy. The other two patients underwent an open surgical procedure (1 patient with the tumor size large than 6 cm, and the other patient with bleeding after loosening one clip). The rate of intraoperative subcutaneous emphysema was 5.88% (1/17), and no death occurred. The operation time was (285+/-30)min on average, the estimated blood loss was (130+/-50)mL, and the hospitalization was (11+/-4)d. One case of obstruction of distal loop happened after the surgery, and the rate was 6.25% (1/16). The patients were followed up for 1 approximately 9 months postoperatively. Trocar puncture-site metastases occurred in one patient. CONCLUSION: Laparoscopic partial gastrectomy is safe and feasible with skillful laparoscopic technique and with restricted indications, and the surgical outcome may be similar to that of the open surgery.