Investigation and verification of the clinical significance and perspective of natural killer group 2 member D ligands in colon adenocarcinoma.

This study investigated and verified the diagnostic and prognostic values of natural killer group 2 member D ligand (NKG2DL) genes in colon adenocarcinoma (COAD). We downloaded NKG2DLs expression data and corresponding clinical parameters from The Cancer Genome Atlas (TCGA) and used bioinformatics techniques to investigate the values of NKG2DLs in COAD. Then, we used the GSE40967 cohort to verify the prognostic value of NKG2DLs. Finally, we verified the ULBP2 expression level in tissues, and also investigated the diagnostic and prognostic values of ULBP2 in COAD. The diagnostic receiver operating characteristic curves showed that ULBP1, ULBP2, ULBP3, and RAET1L had high diagnostic values in COAD [Area Under Curve (AUC) > 0.9]. In TCGA cohort, the univariate and multivariate survival analyses suggested that ULBP2 was correlated with the prognosis of COAD recurrence-free survival (RFS) and overall survival (OS). In GSE40967 cohort, ULBP2 was associated with CC RFS and OS. Reverse transcription-quantitative polymerase chain reaction and immunohistochemistry results showed that ULBP2 was highly expressed in COAD tumor tissues (P < 0.05) and both had diagnostic values (AUC > 0.7). Validated survival analysis showed that the high expression of ULBP2 had a worse prognosis in COAD OS and RFS. Thus, ULBP2 might be an independent diagnostic and prognostic biomarker of COAD.

The Perspective of Diagnostic and Prognostic Values of Lipoxygenases mRNA Expression in Colon Adenocarcinoma.

BACKGROUND: This study was mainly to explore and study the potential application of lipoxygenases (ALOX) family genes in the diagnostic and prognostic values of colon adenocarcinoma (COAD). METHODS: Data sets related to the ALOX genes of COAD were obtained from The Cancer Genome Atlas and the University of California, Santa Cruz Xena browser. Then, the relevant biological information was downloaded from the public data platform. Finally, the bioinformatics technologies and clinical verification were employed to comprehensively analyze the potential values of ALOX genes. RESULTS: The Pearson correlation analysis indicated that there were correlations among ALOXE3, ALOX5, ALOX12, and ALOX12B. The diagnostic receiver operating characteristic (ROC) curves suggested that ALOXE3 and ALOX12 had significant diagnosis in COAD: ALOXE3; P<0.001, area under curve (AUC) 95%CI:=0.818 (0.773-0.862) and ALOX12; P<0.001, AUC 95%CI=0.774 (0.682-0.807). Besides, the verification study indicated that ALOX12 had a diagnostic value in COAD. Finally, our multivariate survival analysis and comprehensive prognosis of ALOX genes in COAD suggested that the ALOXE3 and ALOX12 were associated with COAD overall survival: ALOXE3; P=0.025, HR 95%CI=1.765 (1.074-2.901), ALOX12; P=0.046, HR 95%CI=1.680 (1.009-2.796), and the low expression of ALOXE3 and ALOX12 had a favorable prognosis of COAD (all P<0.05); on the contrary, the high regulation of them increased the risk of death. CONCLUSION: In our study, we observed that the mRNA expressions of ALOX genes were associated with the diagnosis and prognosis of COAD. The results of the diagnostic analysis suggested that ALOX12 might have a diagnosis value in COAD. Besides, our comprehensive prognosis analysis indicated that ALOXE3 combined ALOX12 might serve as potential prognosis biomarkers for COAD.

Distinct diagnostic and prognostic values of γ-aminobutyric acid type A receptor family genes in patients with colon adenocarcinoma.

In the present study, the significance of GABAA genes in colon adenocarcinoma (COAD) were investigated from the view of diagnosis and prognosis. All data were achieved from The Cancer Genome Atlas. Overall survival was analyzed by the Kaplan-Meier analyses and Cox regression model and the hazard ratios and 95% confidence interval were calculated for computation. The Database for Annotation, Visualization and Integrated Discovery, and the Biological Networks Gene Ontology (BiNGO) softwares were applied to assess the biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) was used for pathway analysis to predict the biological function of GABAA genes. The associated Gene Ontology and KEGG pathways were conducted by Gene Set Enrichment Analysis (GSEA). From receiver operating characteristics curves analysis, it was found that the expression of GABR, γ-aminobutyric acid type A receptor GABRA2, GABRA3, GABRB2, GABRB3, GABRG2, GABRG3, GABRD, GABRE were correlated with COAD occurrence [P<0.0001, area under the curve (AUC)>0.7]. The low expression of the GABRB1, GABRD, GABRP and GABRQ in genes after tumor staging adjustment were positively correlated with the overall survival rate [P=0.049, hazard ratio (HR)=1.517, 95% confidence interval (CI)=1.001-2.297; P=0.006, HR=1.807, 95% CI=1.180-2.765; P=0.005, HR=1.833, 95% CI=1.196-2.810; P=0.034, HR=1.578, 95% CI=1.036-2.405). GSEA showed enrichment of cell matrix adhesion, integrin binding, angiogenesis, endothelial growth factor and endothelial migration regulation in patients with COAD with GABRD overexpression. GABRB1, GABRD, GABRP and GABRQ were associated with the prognostic factors of COAD. The expression levels of GABRA2, GABRA3, GABRB2, GABRB3, GABRG2, GABRD and GABRE may allow differentiation between tumor tissues and adjacent normal tissues.

The prognostic value of the postoperative serum CEA levels/preoperative serum CEA levels ratio in colorectal cancer patients with high preoperative serum CEA levels.

PURPOSE: This study aimed to assess the prognostic value of the postoperative serum carcinoembryonic antigen (CEA) levels/preoperative serum CEA levels ratio (CEA ratio) in colorectal cancer (CRC) patients with high preoperative serum CEA levels and to identify the optimal prognostic cutoff value. PATIENTS AND METHODS: The medical records of 187 CRC patients in a single center who underwent surgery between September 2012 and September 2014 were retrospectively reviewed. CEA ratio was defined as the ratio between the postoperative serum CEA and preoperative serum CEA. The optimal cutoff values for the CEA ratio were determined by time-dependent receiver operating characteristic (ROC) curve analyses. The Chi-square test or Fisher's exact probability test were used to test the correlation between CEA ratio and clinicopathological characteristics. Univariate, multivariate, and subgroup Cox proportional hazards analysis were used to identify independent prognostic factors. Kaplan-Meier method was used for establishing survival curves. RESULTS: The median follow-up time was 62 months (range 3-88 months). The optimal CEA ratio cutoff value closely related to disease-free survival was 0.295. In the Chi-square test, the CEA ratio was associated with pN stage (p=0.003) and postoperative CEA (p<0.001). In the multivariate analysis, the CEA ratio was an independent prognostic factor for disease-free survival (p=0.003, HR 2.300 [95% CI: 1.326-3.988]) and cancer-special survival (p=0.003, HR 2.525 [95% CI: 1.381-4.614]). The CEA ratio reflected the prognosis of CRC patients more accurately than postoperative CEA levels alone, and the CEA ratio of 0.295 was more likely to reflect the prognosis than other cutoff values. CONCLUSION: The CEA ratio is a simple and useful tool for further forecasting the prognosis of CRC patients with high preoperative CEA levels and may help develop strategies for the postoperative treatment of CRC patients.

NOD2 Suppresses Colorectal Tumorigenesis via Downregulation of the TLR Pathways.

Although NOD2 is the major inflammatory bowel disease susceptibility gene, its role in colorectal tumorigenesis is poorly defined. Here, we show that Nod2-deficient mice are highly susceptible to experimental colorectal tumorigenesis independent of gut microbial dysbiosis. Interestingly, the expression of inflammatory genes and the activation of inflammatory pathways, including NF-κB, ERK, and STAT3 are significantly higher in Nod2-/- mouse colons during colitis and colorectal tumorigenesis, but not at homeostasis. Consistent with higher inflammation, there is greater proliferation of epithelial cells in hyperplastic regions of Nod2-/- colons. In vitro studies demonstrate that, while NOD2 activates the NF-κB and MAPK pathways in response to MDP, it inhibits TLR-mediated activation of NF-κB and MAPK. Notably, NOD2-mediated downregulation of NF-κB and MAPK is associated with the induction of IRF4. Taken together, NOD2 plays a critical role in the suppression of inflammation and tumorigenesis in the colon via downregulation of the TLR signaling pathways.

[Clinical, endoscopic and pathological features of primary colorectal non-Hodgkin lymphoma: 24 cases report].

OBJECTIVE: To investigate the clinical, endoscopic and pathological features in primary colorectal non-Hodgkin lymphoma. METHODS: Twenty-four cases of primary colorectal non-Hodgkin lymphoma were studied retrospectively. RESULTS: The main clinical symptoms were abdominal pain, abdominal mass, loss of weight, fever, bloody stools and altered bowel habits. There were 6 cases (25.0%) involving two or more lesion sites, including three cases showing continuous skip-distribution from sigmoid colon to ascending colon, one case showing the homologous manifestation from rectum to cecum, one case involving ascending colon and rectum, and the last one involving sigmoid colon and rectum. There were 18 cases involving single lesion site and the caecum was the most frequently affected site (44.4%, 8 cases). The major endoscopic phenotypes were ulcer (39.1%), bossing (43.5%) and infiltrating (17.4%). The major pathology types were diffuse large B-cell lymphoma (11/24, 45.8%), intestinal T-cell lymphoma (8/24, 33.3%), and mucosa-associated lymphoid tissue lymphoma (MALT) (3/24, 12.5%). 2 of 24 cases (8.3%) were not decided. Twenty-one patients were treated surgically, containing fifteen radical excisions, one local excision, four palliative excisions and one exploratory laparotomy. Sixteen postoperative patients accepted CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or COP (cyclophosphamide, vincristine, prednisone) chemotherapy, and three patients abandoned treatment. Twenty-one patients were followed up and the 5-year survival rate was 37.7%. CONCLUSION: The clinical features of primary colorectal non-Hodgkin's lymphoma have no specificity. Ulcer and bossing are the two major morphologic manifestations of endoscopic. Diffuse large B-cell lymphoma and intestinal T-cell lymphoma are the main pathological types. Comprehensive treatment of surgery and chemotherapy are effective methods for primary colorectal non-Hodgkin lymphoma.

[Influence and significance of preoperative intraarterial infusion chemotherapy combined with radiotherapy on survivin, p53 and Bax expression in low rectal carcinoma].

BACKGROUND & OBJECTIVE: Recently, neoadjuvant therapy has attracted more attention, but the influence of preoperative intraarterial infusion chemotherapy (PRAC) combined with radiotherapy on Survivin expression in rectal carcinoma is unclear. This study was to investigate the effect of PRAC or radiotherapy on Survivin, P53, and Bax expression in low rectal cancer. METHODS: A total of 60 patients with low rectal carcinoma were randomized into 3 groups: 19 received PRAC combined with preoperative radiotherapy (radiochemotherapy group), 15 received preoperative radiotherapy alone (radiotherapy group), and 26 received operation alone (control group). PRAC was performed using Seldinger technique. Preoperative radiotherapy was performed with a total dose of 20 Gy in 5 days, and superadded 30 Gy after operation. Control group received postoperative radiotherapy with a total dose of 50 Gy. The expression of Survivin, P53, and Bax was examined by immunohistochemistry. RESULTS: After neoadjuvant therapy, there was no significant difference in the positive rates of Survivin, P53, and Bax among the 3 groups. In radiochemotherapy group, the positive rate of Survivin was reduced from 63.16% before neoadjuvant therapy to 26.32% after operation (P<0.05), and the overexpression rate of P53 was reduced from 57.89% to 26.32% (P<0.05). In radiotherapy group, the overexpression rate of Survivin was reduced from 53.33% to 13.33% (P<0.05), but there was no significant change in the positive rate of P53. The positive rate of Bax was slightly increased after operation in above 2 groups. In these 2 groups, the median survival time was significantly longer in the patients with reduced Survivin expression than in those with increased Survivin expression (50.05 months vs. 42.61 months, P<0.01). Survivin expression was not obviously related to Bax and P53 expression (P>0.05). CONCLUSION: Neoadjuvant therapy could decrease the levels of P53 and Survivin expression, might enhance the level of Bax expression, and consequently accelerate cancer cell apoptosis and achieve a better short-term curative effect on low rectal cancer.