Identification of angiogenesis-related subtypes, the development of a prognosis model, and features of tumor microenvironment in colon cancer.

Angiogenesis is associated with tumor progression, prognosis, and treatment effect. However, the angiogenesis' underlying mechanisms in the tumor microenvironment (TME) still remain unclear. Understanding the dynamic interactions between angiogenesis and TME in colon adenocarcinoma (COAD) is necessary. We downloaded the transcriptome data and corresponding clinical data of colon cancer patients from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases, respectively. We identified two distinct angiogenesis-related molecular subtypes (subtype A and subtype B) and assessed the clinical features, prognosis, and infiltrating immune cells of patients in the two subtypes. According to the prognostic differential genes, we defined two different gene clusters to further explore the correlation between angiogenesis and tumor heterogeneity. Then, we construct the prognostic risk scoring model angiogenesis-related gene (ARG-score) including seven genes (ARMCX2, latent transforming growth factor ß binding protein 1, ADAM8, FABP4, CCL11, CXCL11, ITLN1) using Lasso-multivariate cox method. We analyzed the correlation between ARG-score and prognosis, clinicopathological features, TME, molecular feature, cancer stem cells (CSCs), and microsatellite instability (MSI) status. To assess the application value of ARG-score in clinical treatment, immunophenotype score was used to predict patients' immunotherapy response in colon cancer. We found the mutations of ARGs in TCGA-COAD dataset from genetic levels and discussed their expression patterns based on TCGA and GEO datasets. We observed important differences in clinicopathological features, prognosis, immune feature, molecular feature between the two molecular subgroups. Then, we established an ARG-score for predicting OS and validated its predictive capability. A high ARG-score characterized by higher transcription level of ARGs, suggested lower MSI-high (MSI-H), lower immune score, and worse clinical stage and survival outcome. Additionally, the ARG-score was remarkably related to the CSCs index and immunotherapy sensitivity. We found two new molecular subtypes and two gene clusters based on ARGs and established an ARG-score. Multilayered analysis revealed that ARGs were remarkably correlated to the heterogeneity of colon cancer patients and explained the process of tumorigenesis and progression better. The ARG-score can help us better assess patients' survival outcomes and provide guidance for individualized treatment.

NOP58 induction potentiates chemoresistance of colorectal cancer cells through aerobic glycolysis as evidenced by proteomics analysis.

Introduction: The majority of individuals diagnosed with advanced colorectal cancer (CRC) will ultimately acquire resistance to 5-FU treatment. An increasing amount of evidence indicates that aerobic glycolysis performs a significant function in the progression and resistance of CRC. Nevertheless, the fundamental mechanisms remain to be fully understood. Methods: Proteomic analysis of 5-FU resistant CRC cells was implemented to identify and determine potential difference expression protein. Results: These proteins may exhibit resistance mechanisms that are potentially linked to the process of aerobic glycolysis. Herein, we found that nucleolar protein 58 (NOP58) has been overexpressed within two 5-FU resistant CRC cells, 116-5FuR and Lovo-5FuR. Meanwhile, the glycolysis rate of drug-resistant cancer cells has increased. NOP58 knockdown decreased glycolysis and enhanced the sensitivity of 116-5FuR and Lovo-5FuR cells to 5FU. Conclusion: The proteomic analysis of chemoresistance identifies a new target involved in the cellular adaption to 5-FU and therefore highlights a possible new therapeutic strategy to overcome this resistance.

Effect of intra-operative chemotherapy with 5-fluorouracil and leucovorin on the survival of patients with colorectal cancer after radical surgery: a retrospective cohort study.

BACKGROUND: The effect of intra-operative chemotherapy (IOC) on the long-term survival of patients with colorectal cancer (CRC) remains unclear. In this study, we evaluated the independent effect of intra-operative infusion of 5-fluorouracil in combination with calcium folinate on the survival of CRC patients following radical resection. METHODS: 1820 patients were recruited, and 1263 received IOC and 557 did not. Clinical and demographic data were collected, including overall survival (OS), clinicopathological features, and treatment strategies. Risk factors for IOC-related deaths were identified using multivariate Cox proportional hazards models. A regression model was developed to analyze the independent effects of IOC. RESULTS: Proportional hazard regression analysis showed that IOC (hazard ratio [HR]=0.53, 95% confidence intervals [CI] [0.43, 0.65], P  < 0.001) was a protective factor for the survival of patients. The mean overall survival time in IOC group was 82.50 (95% CI [80.52, 84.49]) months, and 71.21 (95% CI [67.92, 74.50]) months in non-IOC group. The OS in IOC-treated patients were significantly higher than non-IOC-treated patients ( P  < 0.001, log-rank test). Further analysis revealed that IOC decreased the risk of death in patients with CRC in a non-adjusted model (HR=0.53, 95% CI [0.43, 0.65], P  < 0.001), model 2 (adjusted for age and gender, HR=0.52, 95% CI [0.43, 0.64], P  < 0.001), and model 3 (adjusted for all factors, 95% CI 0.71 [0.55, 0.90], P  = 0.006). The subgroup analysis showed that the HR for the effect of IOC on survival was lower in patients with stage II (HR = 0.46, 95% CI [0.31, 0.67]) or III disease (HR=0.59, 95% CI [0.45, 0.76]), regardless of pre-operative radiotherapy (HR=0.55, 95% CI [0.45, 0.68]) or pre-operative chemotherapy (HR=0.54, 95% CI [0.44, 0.66]). CONCLUSIONS: IOC is an independent factor that influences the survival of CRC patients. It improved the OS of patients with stages II and III CRC after radical surgery. TRIAL REGISTRATION: chictr.org.cn, ChiCTR 2100043775.

Potential impact of platelet-to-lymphocyte ratio on prognosis in patients with colorectal cancer: A systematic review and meta-analysis.

Background: Numerous studies have confirmed that inflammation promotes the occurrence, development and prognosis of colorectal cancer (CRC). Objective: This study focuses on the potentially prognostic value of the platelet-to-lymphocyte ratio (PLR) in CRC patients. Data Sources: This study was registered at PROSPERO (ID: CRD42020219215). Relative studies were searched on PubMed, Cochrane Library, Embase, Web of Science, and clinical trial databases by two back-to-back reviewers. Study Selection and Intervention: Studies were screened according to the predetermined inclusion and exclusion criteria, comparing prognosis differences between low PLR levels and high PLR levels for CRC patients. Main Outcome Measures: Studies were integrated and compared to analyze the value of PLR in predicting overall survival (OS), progression-free survival (PFS), cancer-specific survival (CSS), disease-free survival (DFS) and recurrence-free survival (RFS) of CRC. Results: Outcomes were compared using Review Manager (version 5.4) software from Cochrane Collaboration. A total of 27 literary works, including 13,330 patients, were incorporated into our study. The final results showed that higher PLR levels had worse OS (hazard ratio [HR] = 1.40, 95% confidence interval [CI] = 1.21-1.62, P < 0.00001), DFS (HR = 1.44, 95% CI = 1.09-1.90, P = 0.01) and RFS (HR = 1.48, 95% CI = 1.13-1.94, P = 0.005) than lower PLR levels, respectively. However, there was no evidence of significance for PFS (HR = 1.14, 95% CI = 0.84-1.54, P = 0.40) and CSS (HR = 1.16, 95% CI = 0.88-1.53, P = 0.28) in the final meta-analysis. Limitations: Our study has the following limitations. First of all, we only included literature published in English, which means that some publication bias may be inevitable. In addition, our study used aggregate data, not individual data; furthermore, we did not define the exact cut-off value representing the PLR level. Conclusion: An elevated PLR seems to be an adverse prognostic factor affecting survival outcomes in patients with CRC. Meanwhile, more prospective studies are required to confirm our conclusion.PROSPERO ID: CRD42020219215.

Nomogram for benign anastomotic stricture after surgery for rectal cancer.

BACKGROUND: Benign anastomotic stricture remains among the most prevalent complications following surgery for rectal cancer. OBJECTIVE: This study is aimed at identifying risk factors of anastomotic stricture as well as generating an effective nomogram for the stricture. METHODS: Design: This is a retrospective study. SETTING: This study was conducted from January 2015 to December 2019 in a single tertiary center for rectal cancer. PATIENTS: A total of 117 rectal cancer patients after surgery without recurrence were enrolled in this study, of which 39 with anastomotic stricture and 78 without stricture. MAIN OUTCOME MEASURES: Their clinical and pathological data were collected. Multiple logistic regression analysis was conducted to identify risk factors for anastomotic stricture and to generate the nomogram prediction model. RESULTS: Multivariate analysis of the primary cohort led to the identification of LCA (left colic artery) preservation (OR, 0.074; P = 0.0015), protective stoma (OR, 5.353; P = 0.012), anastomotic leakage (OR, 12.027; P = 0.005), and anastomotic distance (OR, 7.578; P = 0.012) as independent risk factors for anastomotic stricture. The following predictive model was derived: Logit (anastomotic stricture) = 0.074∗ LCA + 5.353∗ Protective stoma +12.027∗ Anastomotic leakage + 7.578∗ Anastomotic distance. Assessment of the predictive model revealed that the area under the curve (AUC) was 0.871, while the cutoff value was 15.444 with a sensitivity of 64.1% and a specificity of 94.8%. LIMITATIONS: The main limitation is the research design of a retrospective and case-controlled study with a small sample size from a single center. CONCLUSIONS: LCA preservation, protective stoma, anastomotic leakage, and anastomotic distance may affect the occurrence of anastomotic stricture following surgery for rectal cancer. The nomogram model generated in the present study can be valuable in the prediction of anastomotic stricture. This study has been registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/, ChiCTR 2100043775).

Life stages and morphological variations of Limnocythere inopinata (Crustacea, Ostracoda) from Lake Jiang-Co (northern Tibet): a bioculture experiment.

Limnocythere inopinata (Baird, 1843) is a Holarctic species, abundant in a number of Recent and fossil ostracod assemblages, and has many important taxonomic and (paleo)ecological applications. However, the life cycle and morphological characteristics of the living L. inopinata are still unclear. A bioculture experiment was designed to study life stages and morphological variations from stage A-8 to adult in this species. The living animals were collected from Lake Jiang-Co, in the northern Tibetan Plateau. Results reveal that this species possesses a special growth pattern with the maximum size increase occurring at the transition from the instars A-5 to A-4. The growth pattern deviates from Brooks' rule and one population from Lake Dali, eastern Mongolian Plateau. This suggests that the life history of L. inopinata may be influenced by environmental factors. Some morphological differences between Lake Jiang-Co and European populations of L. inopinata are also uncovered. Therefore, a detailed morphological description of this population is provided, but refrain from erecting a new species at the present stage because those differences appear to be inconsistent.

Distribution, Contents, and Types of Mycosporine-Like Amino Acids (MAAs) in Marine Macroalgae and a Database for MAAs Based on These Characteristics.

Mycosporine-like amino acids (MAAs), maximally absorbed in the wavelength region of 310-360 nm, are widely distributed in algae, phytoplankton and microorganisms, as a class of possible multi-functional compounds. In this work, based on the Web of Science, Springer, Google Scholar, and China national knowledge infrastructure (CNKI), we have summarized and analyzed the studies related to MAAs in marine macroalgae over the past 30 years (1990-2019), mainly focused on MAAs distribution, contents, and types. It was confirmed that 572 species marine macroalgae contained MAAs, namely in 45 species of Chlorophytes, 41 species of Phaeophytes, and 486 species of Rhodophytes, and they respectively belonged to 28 orders. On this basis, we established an open online database to quickly retrieve MAAs in 501 species of marine macroalgae. Furthermore, research concerning MAAs in marine macroalgae were analyzed using CiteSpace. It could easily be seen that the preparation and purification of MAAs in marine macroalgae have not been intensively studied during the past 10 years, and therefore it is necessary to strengthen the research in the preparation and purification of MAA purified standards from marine macroalgae in the future. We agreed that this process is not only interesting, but important due to the potential use of MAAs as food and cosmetics, as well as within the medicine industry.

Antialgal compounds with antialgal activity against the common red tide microalgae from a green algae Ulva pertusa.

Nine antialgal active compounds, (i.e. trehalose (1), twenty-two methyl carbonate (2), (-)-dihydromenisdaurilide (3), 3,7,11,15-tetramethyl-2-hexadecen-1-ol (4), isophytol (5), 8-hexadecenol (6), 17-hydroxyheptadecanoic acid (7), trans-asarone (8) and 2-amino-3-mercaptopropanoic acid (9)) were isolated from Ulva pertusa for the first time by sephadex LH-20 column chromatography, silica gel column chromatography and repeated preparative TLC. Except for compound 4, all compounds represented novel isolated molecules from marine macroalgae. Further, antialgal activities of these compounds against Amphidinium carterae, Heterosigma akashiwo, Karenia mikimitoi, Phaeocystis globosa, Prorocentrum donghaiense and Skeletonema costatum were investigated for the first time. Results showed these nine compounds have selectivity antialgal effects on all test red tide microalgae, and antialgal activities against red tide microalgae obviously enhanced with the increase of concentration of antialgal compounds. Based on this, EC50-96 h values of these nine compounds for six red tide microalgae were obtained for the first time. By analyzing and comparing EC50-96 h values, it has been determined that seven compounds (1, 3, 4, 6, 7, 8 and 9) showed the superior application potential than potassium dichromate or gossonorol and other six compounds as a characteristic antialgal agent against Heterosigma akashiwo, Karenia mikimitoi and Prorocentrum donghaiense. Overall this study has suggested that green algae Ulva pertusa is a new source of bioactive compounds with antialgal activity.

Isolation and purification of antialgal compounds from the red alga Gracilaria lemaneiformis for activity against common harmful red tide microalgae.

Seven antialgal compounds (1-7) were successfully isolated from the red alga Gracilaria lemaneiformis through a combination of silica gel column chromatography and repeated preparative thin-layer chromatography. On the basis of the spectral data, the compounds were identified as gossonorol (1), 7,10-epoxy-ar-bisabol-11-ol (2), glycerol monopalmitate (3), stigmasterol (4), 15-hydroxymethyl-2, 6, 10, 18, 22, 26, 30-heptamethyl-14-methylene-17-hentriacontene (5), 4-hydroxyphenethyl alcohol (6), and margaric acid (7). These seven compounds were isolated from G. lemaneiformis for the first time, while the compounds 4, 6, and 7 were isolated from marine macroalgae for the first time. Furthermore, a quantitative relationship between the inhibition of algal growth and the concentration of each antialgal compound was determined and important parameters for future practical HAB control, e.g., EC50-96h, were also obtained. The results indicated that isolated compounds 1-7 possess selective antialgal activity against the growth of several red tide microalgae (including Amphidinium carterae, Heterosigma akashiwo, Karenia mikimitoi, Phaeocystis globsa, Prorocentrum donghaiense, and Skeletonema costatum). Their antialgal activity against test red tide microalgae has not been previously reported. Furthermore, the EC50-96h of one or more of the compounds towards the tested red microalgae was not only significantly less than 10 µg/mL but also was smaller than that of the characteristic antialgal agent potassium dichromate. The study demonstrates that compounds 1-7 possess significant application potential as antialgal agents against several harmful red tide microalgae.

Isolation, purification, and identification of antialgal substances in green alga Ulva prolifera for antialgal activity against the common harmful red tide microalgae.

Ten compounds (1~10) were successfully isolated from green algae Ulva prolifera through the combination of silica gel column chromatography, Sephadex LH-20 column chromatography and repeated preparative thin-layer chromatography. These ten compounds showed antialgal activity against red tide microalgae. Among them, compounds 3, 6, and 7 showed stronger antialgal activity against red tide microalgae. Furthermore, their structure was identified on the basis of spectroscopic data. There are three glycoglycerolipids: 1-O-octadecanoic acid-3-O-ß-D-galactopyranosyl glycerol (2), 1-O-palmitoyl-3-O-ß-D-galactopyranosyl glycerol (4), and 1-O-palmitoyl-2-O-oleoyl-3-O-ß-D-galactopyranosyl glycerol (5); two monoglycerides: glycerol monopalmitate (1), 9-hexadecenoic acid, 2,3-dihydroxypropyl ester (3); two terpenoids: loliolide (6) and lsololiolide (7); one lipid-soluble pigments: zeaxanthin (8); one sterol: cholest-5-en-3-ol (9); and one alkaloid: pyrrolopiperazine-2,5-dione (10). These compounds were isolated from U. prolifera for the first time, and compounds 2, 3, 5, and 8 were isolated from marine macroalgae for the first time.

The isolation and antioxidant activity of polysaccharides from the marine microalgae Isochrysis galbana.

Three polysaccharides, IPSI-A, IPSI-B and IPSII, were successfully isolated from the marine microalgae Isochrysis galbana through a combination of anion-exchange column chromatography and repeated gel chromatography. These three polysaccharides were demonstrated to have moderate scavenging activities against superoxide and hydroxyl radicals and moderate reductive power in a concentration-dependent manner. The IPSII demonstrated more effective antioxidant activities than IPSI-A and IPSI-B. IPSII had a molecular weight of 15.934 kDa belonging to a ß-type heteropolysaccharide with a pyran group and primarily contained mannose with variable amounts of glucose, galactose and rhamnose based on an analysis of infrared spectroscopy (IR), electrospray ionization-mass spectrometry (ESI-MS) and (1)H nuclear magnetic resonance ((1)H NMR).