Construction of a DDR-related signature for predicting of prognosis in metastatic colorectal carcinoma.

Background: Colorectal cancer (CRC) is the third most prevalent malignancy and the one of most lethal cancer. Metastatic CRC (mCRC) is the third most common cause of cancer deaths worldwide. DNA damage response (DDR) genes are closely associated with the tumorigenesis and development of CRC. In this study, we aimed to construct a DDR-related gene signature for predicting the prognosis of mCRC patients. Methods: The gene expression and corresponding clinical information data of CRC/mCRC patients were obtained from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. A prognostic model was obtained and termed DDRScore by the multivariate Cox proportional hazards regression in the patients with mCRC. The Kaplan-Meier (K-M) and Receiver Operating Characteristic (ROC) curves were employed to validate the predictive ability of the prognostic model. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were performed for patients between the high-DDRscore and low-DDRscore groups. Results: We constructed a prognostic model consisting of four DDR-related genes (EME2, MSH4, MLH3, and SPO11). Survival analysis showed that patients in the high-DDRscore group had a significantly worse OS than those in the low-DDRscore group. The area under the curve (AUC) value of the ROC curve of the predictive model is 0.763 in the training cohort GSE72970, 0.659 in the stage III/IV colorectal cancer (CRC) patients from The Cancer Genome Atlas (TCGA) data portal, and 0.639 in another validation cohort GSE39582, respectively. GSEA functional analysis revealed that the most significantly enriched pathways focused on nucleotide excision repair, base excision repair, homologous recombination, cytokine receptor interaction, chemokine signal pathway, cell adhesion molecules cams, ECM-receptor interaction, and focal adhesion. Conclusion: The DDRscore was identified as an independent prognostic and therapy response predictor, and the DDR-related genes may be potential diagnosis or prognosis biomarkers for mCRC patients.

Expression of stromal cell-derived factor 1 and CXCR7 ligand receptor system in pancreatic adenocarcinoma.

BACKGROUND: Stromal cell-derived factor 1 (SDF-1) is a chemokine that is expressed in some cancer cells and is involved in tumor cell migration and metastasis. CXCR7, a novel receptor for SDF-1, has been identified recently. Research has demonstrated that SDF-1/CXCR7 interaction could play an important role in cancer progression. In this study, we aimed to investigate the expression of the SDF-1/CXCR7 ligand receptor system and the relationship between this expressions and clinicopathological characteristics in pancreatic adenocarcinoma. METHODS: Expressions of SDF-1 and CXCR7 in 64 cases of pancreatic adenocarcinoma tissue and 24 cases of normal pancreatic tissue were detected immunohistochemically. RESULTS: Expressions of SDF-1 and CXCR7 were negative in normal pancreatic tissues. Respectively, positive expression rates of SDF-1 and CXCR7 in pancreatic adenocarcinoma were 45.3% and 51.6%. The expression of SDF-1 correlated with histological grades; the expression rate in moderate to low differentiation was higher than in high differentiation (P<0.05). The expression of CXCR7 positively correlated with lymph node metastasis (P<0.05). A log-rank test showed that the expression of SDF-1+/CXCR7+ correlated with poor prognosis (P<0.05). CONCLUSIONS: The SDF-1/CXCR7 receptor ligand system may take part in invasive progression and metastasis of pancreatic adenocarcinoma, and might be useful as an index for evaluating invasiveness and prognosis.

Molecular epidemiology of Orientia tsutsugamushi in chiggers and ticks from domestic rodents in Shandong, northern China.

BACKGROUND: Scrub typhus is endemic to a 13,000,000-km² area of the Asia-Pacific region, and causes an annual incidence of 1 million people. The mortality rate of scrub typhus ranges from 6.1% to 25% in Southeast Asia. Natural infection of Orientia tsutsugamushi has been identified in domestic rodents in Shandong Province. However, infestation of chiggers and ticks on the domestic rodents and prevalence and genotypes of O. tsutsugamushi in these Acarina remain unclear. METHODS: During September 2010 to March 2012, 3134 chiggers and 89 ticks were collected from domestic rodents captured in three counties of Shandong Province. We amplified and sequenced the 56-kDa type-specific antigen gene of O. tsutsugamushi from DNA samples of these Acarina and designated to genotype according to sequence analysis. RESULTS: Overall, the infestation rate of chiggers on domestic rodents was 17.0%, and the chigger index was 5.38. The infestation rate of ticks on rodents was 3.1%. Natural infection of O. tsutsugamushi was found in Leptotrombidium taishanicum, L. linhuaikongense, L. intermedium, L. scutellare, L. palpale, and Ixodes spp., the minimum positive rates of which were 5.9%, 3.2%, 1.2%, 0.8%, 0.8%, and 2.2%, respectively. Kawasaki-like genotypes were predominant in chiggers and ticks on domestic rodents, which were detected from L. taishanicum, L. intermedium, L. scutellare, L. palpale, and Ixodes spp. Shimokoshi-like genotype was detected from L. palpale. CONCLUSIONS: In the present study we investigated the infestation of chiggers and ticks on domestic rodents in Shandong Province, and identified the prevalence and genotypes of O. tsutsugamushi in the Acarina. Infestation of vector chiggers in domestic rodents, prevalence of O. tsutsugamushi in infested chiggers, and high nucleotide homologies among the O. tsutsugamushi sequences from the Acarina, their animal hosts and scrub typhus patients, implied that domestic rodents may play an important role in the transmission of scrub typhus in Shandong, China. Further studies are needed to verify the vector significance of chiggers and ticks that tested positive for O. tsutsugamushi, and to assess the risk of human exposure to chiggers and ticks on domestic rodents.

Expression of stromal cell-derived factor 1 and CXCR7 in papillary thyroid carcinoma.

Stromal cell-derived factor 1 (SDF-1) is a chemokine that is expressed in some cancer cells and is involved in tumor cell migration and metastasis. CXCR7, a novel receptor for SDF-1, has been identified recently. Researches demonstrated that interaction between SDF-1 and CXCR7 could play an important role in cancer progression. In this study, we aimed to investigate the expressions of SDF-1 and CXCR7 and the relationship between their expressions and clinicopathological characteristics in papillary thyroid carcinoma (PTC). Expressions of SDF-1 and CXCR7 in 33 cases of thyroid benign lesion tissue and 79 cases of PTC tissue and peritumoral non-malignant tissue were detected by immunohistochemical staining. Expressions of SDF-1 and CXCR7 were negative in peritumoral non-malignant tissues. Respectively, positive expression rates of SDF-1 and CXCR7 were 69.6 and 65.8 % in PTC, 12.1 and 30.3 % in thyroid benign tissue. The expression of SDF-1 and CXCR7 were positively correlated with lymph node metastasis. SDF-1 and CXCR7 expressions were related with the lymph nodes metastasis of PTC.