Preoperative albumin-to-globulin ratio and prognostic nutritional index predict the prognosis of colorectal cancer: a retrospective study.

The immunonutritional status has important effects on outcomes for cancer patients. Albumin-to-globulin ratio (AGR) and the prognostic nutrition index (PNI) are often used to assess the immunonutritional status of cancer patients. However, the clinical significance of these factors in colorectal cancer (CRC) remains unclear. We aimed to evaluate the clinical significance of the AGR and PNI in CRC. We reviewed the clinical data of 511 patients with CRC in two hospitals. Data from one institution was used as the training cohort. The optimal cutoff values for AGR and PNI in the training cohort were 1.4 and 48.65, respectively. Patients in both the low AGR and low PNI groups had poor overall survival (OS) and progression-free survival (PFS), while those in the low AGR-low PNI group had the lowest OS and PFS. Multivariate analysis revealed that preoperative AGR, preoperative PNI, gross type, and TNM stage were independent prognostic factors influencing OS in patients with CRC. Preoperative AGR, preoperative PNI, and TNM stage were independently associated with PFS in patients with CRC. According to the results of multivariate analysis in the training cohort, we developed the nomograms for OS and PFS and performed internal and external validation, which showed good prediction ability of the nomograms. In conclusion, preoperative AGR and PNI can be used as effective indicators to predict survival for patients with CRC. AGR and PNI may help develop effective adjuvant-therapy schedules.

Investigating dysbiosis and microbial treatment strategies in inflammatory bowel disease based on two modified Koch's postulates.

Inflammatory bowel disease (IBD) is a chronic non-specific inflammatory disease that occurs in the intestinal tract. It is mainly divided into two subtypes, i.e., the Crohn's disease (CD) and ulcerative colitis (UC). At present, its pathogenesis has not been fully elucidated, but it has been generally believed that the environment, immune disorders, genetic susceptibility, and intestinal microbes are the main factors for the disease pathogenesis. With the development of the sequencing technology, microbial factors have received more and more attention. The gut microbiota is in a state of precise balance with the host, in which the host immune system is tolerant to immunogenic antigens produced by gut commensal microbes. In IBD patients, changes in the balance between pathogenic microorganisms and commensal microbes lead to changes in the composition and diversity of gut microbes, and the balance between microorganisms and the host would be disrupted. This new state is defined as dysbiosis. It has been confirmed, in both clinical and experimental settings, that dysbiosis plays an important role in the occurrence and development of IBD, but the causal relationship between dysbiosis and inflammation has not been elucidated. On the other hand, as a classic research method for pathogen identification, the Koch's postulates sets the standard for verifying the role of pathogens in disease. With the further acknowledgment of the disease pathogenesis, it is realized that the traditional Koch's postulates is not applicable to the etiology research (determination) of infectious diseases. Thus, many researchers have carried out more comprehensive and complex elaboration of Koch's postulates to help people better understand and explain disease pathogenesis through the improved Koch's postulates. Therefore, focusing on the new perspective of the improved Koch's postulates is of great significance for deeply understanding the relationship between dysbiosis and IBD. This article has reviewed the studies on dysbiosis in IBD, the use of microbial agents in the treatment of IBD, and their relationship to the modified Koch's postulates.

Pan-immune-inflammation value is associated with the clinical stage of colorectal cancer.

Objective: We investigated the clinical significance of preoperative pan-immune-inflammation value (PIV) in patients with colorectal cancer (CRC). Methods: In this retrospective study, 366 cases who underwent surgery for CRC were enrolled. Their clinical data were collected. PIV was calculated with the formula PIV = [neutrophil count (109/L)× platelet count (109/L) × monocyte count (109/L) /lymphocyte count (109/L). Patients were divided into high PIV (> median PIV) and low PIV (< median PIV) groups. The relationship between PIV and clinicopathological features of CRC was investigated. Receiver operating characteristic (ROC) curve was plotted to indicate the value of immune-inflammatory biomarkers (IIBs) in predicting the TNM stage of CRC, and the area under the curve (AUC) was calculated to evaluate the actual clinical value of IIBs. AUC > 0.5 and closer to 1 indicated the better predictive efficacy. The influencing factors of PIV in CRC were analyzed. Results: We found that PIV was positively correlated with tumor size (r = 0.300, p < 0.05), carcinoembryonic antigen (CEA) (r = 0.214, p < 0.05) and carbohydrate antigen 125 (CA-125) (r = 0.249, p < 0.05), but negatively correlated with albumin (Alb) (r = -0.242, p < 0.05). PIV was significantly different in patients with different tumor locations (left or right), surgical methods (laparotomy versus laparoscopic surgery) (p < 0.05), and patients with different pathological T stages, N-stage and TNM stages (p < 0.05). ROC curve analysis of IIBs showed the AUC of PIV was greater than other markers when combined with CEA or carbohydrate antigen 19-9 (CA19-9). Multivariate regression analysis identified T stage, CEA, Alb, and tumor size as the independent influential factors of PIV in CRC. Conclusion: PIV is associated with the tumor stage in patients with CRC, which may be useful in preoperative assessment of CRC.

Correlation of Cancer Stem-Cell Markers OCT4, SOX2, and NANOG with Clinicopathological Features and Prognosis in Operative Patients with Rectal Cancer.

PURPOSE: To investigate the association of cancer stem-cell markers [octamer-binding transcription factor 4 (OCT4), sex determining region Y-box 2 (SOX2), and Nanog homebox (NANOG)] expression with clinicopathological properties and overall survival (OS) in operative rectal cancer (RC) patients receiving adjuvant therapy. MATERIALS AND METHODS: 153 patients with primary RC receiving surgery were enrolled. Tumor tissue and paired adjacent normal tissue sample were collected, and OCT4, SOX2, and NANOG expressions were assessed by immunofluorescent staining. The median follow-up duration was 5.2 years, and the last follow-up date was August 2016. RESULTS: Tumor tissue OCT4 (p<0.001), SOX2 (p=0.003), and NANOG (p<0.001) expressions were higher than those in adjacent tissue. OCT4 expression was positively correlated with pathological grade (R=0.185, p=0.022), tumor size (R=0.224, p=0.005), and N stage (R=0.170, p=0.036). NANOG expression was positively associated with tumor size (R=0.169, p=0.036). Kaplan-Meier suggested that OCT4⁺ was associated with worse OS compared with OCT4? (p<0.001), while no association of SOX2 (p=0.121) and NANOG expressions (p=0.195) with OS was uncovered. Compared with one or no positive marker, at least two positive markers were associated with shorter OS (p<0.001), while all three positive markers were correlated with worse OS compared with two or less positive markers (p<0.001). Multivariate Cox's analysis revealed that OCT4⁺ (p<0.001) and N stage (p=0.046) were independent factors for shorter OS. CONCLUSION: Tumor tissue OCT4 expression was correlated with poor differentiation, tumor size, and N stage, and it can serve as an independent prognostic biomarker in operative patients with RC receiving adjuvant therapy.

Smoking and risk of cholangiocarcinoma: a systematic review and meta-analysis.

Previous studies evaluating the association between smoking and risk of cholangiocarcinoma (CCA) have yielded controversial results. We conducted a meta-analysis to evaluate the association based on available evidence. We searched the databases of Embase, PubMed and Cochrane Central Register of Controlled Trials from inception to April 11, 2017. Studies that investigated the association between smoking and risk of CCA were included. Pooled odds ratio (OR) estimates and 95% confidence intervals (CIs) were calculated using either a random-effects or a fixed-effects model. A total of 22 studies involving 324,333 participants were identified. The summary OR of CCA was 1.31 (95% CI, 1.15 to 1.51) for smokers versus nonsmokers. The increased risk was independent of diabetes mellitus, bilious tract stone disease, and liver cirrhosis. Smokers also had increased risk of intrahepatic CCA (12 studies; OR, 1.31; 95% CI, 1.06 to 1.63) and extrahepatic CCA (12 studies; OR, 1.32; 95% CI, 1.10 to 1.59) compared with nonsmokers. The results of our meta-analysis support the hypothesis that there is a moderate association between cigarette smoking and risk of CCA.

Lysosome-associated protein transmembrane4ß is involved in multidrug resistance processes of colorectal cancer.

Colorectal cancer (CRC) is one of the most common reasons for cancer-associated mortality worldwide. The present study aimed to investigate the drug resistance mechanism of the oxaliplatin (OXA)-resistant HT-29 cell line (HT-29/L-OHP) and examine the expression of lysosome-associated protein transmembrane 4ß (LAPTM4ß), a drug resistance-associated gene. In the present study, a drug concentration gradient method was used to establish the drug-resistant HT-29/L-OHP cell line. Cell apoptosis was analyzed by flow cytometry. LAPTM4ß mRNA expression was examined by reverse transcription-quantitative polymerase chain reaction analysis and LAPTM4ß-35 expression was examined by western blot analysis. Cell morphology of the HT-29/L-OHP drug-resistant cell line was examined. The results indicated that the intercellular space among HT-29 cells was small, with aggregative growth while the intercellular space among HT-29/L-OHP cells was large, with scattered growth. The apoptotic rate in HT-29/L-OHP cells (11.7%) was significantly lower compared with that in HT-29 cells (17.7%) (P<0.05). LAPTM4ß mRNA expression in HT-29/L-OHP cells was significantly increased compared with that in HT-29 cells (P<0.05). The relative expression of LAPTM4ß-35 protein in HT-29/L-OHP cells was significantly higher compared with that inHT-29 cells (P<0.05). In conclusion, LAPTM4ß may be involved in the multidrug resistance processes of CRC. Therefore, LAPTM4ß may serve as a novel biomarker for drug resistance of CRC.

Association between adiponectin polymorphisms and the risk of colorectal cancer.

PURPOSE: To discuss the association between adiponectin (ADIPOQ) gene rs2241766 and rs1501299 polymorphisms and the risk of colorectal cancer, and to analyze the role of the interaction between these two loci and environmental factors in colorectal cancer pathogenesis. METHODS: The case-control study was performed with a 1:1 match. A self-designed questionnaire was used to perform a face-to-face survey with 600 new primary colorectal cancer cases confirmed by histopathology as well as 600 cases of people receiving a physical examination at the same time. The general information, lifestyle, and diet habits, etc. were collected from two groups of study subjects. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to identify ADIPOQ rs2241766 and rs1501299 genotypes. RESULTS: After adjusting for factors such as colorectal cancer family history, body-mass index (BMI), daily sedentary time, weekly red meat intake frequency, as well regular tea drinking, conditional logistic regression analysis indicated that rs2241766 TG+GG carriers had a higher risk of colorectal cancer than TT carriers (OR=1.433, 95% CI: 1.014-1.985); rs1501299 GT+TT carriers had a lower risk of colorectal cancer than GG carriers (OR=0.723, 95% CI: 0.531-0.902). Generalized multifactor dimensionality reduction analysis showed that ADIPOQ rs2241766 and rs1501299 could have interaction with red meat intake (p=0.001). CONCLUSION: ADIPOQ rs2241766 and rs1501299 single nucleotide polymorphisms (SNPs) could be associated with colorectal pathogenesis and could have interactions with red meat intake. Both factors impact colorectal cancer occurrence.