Prognostic value of systemic inflammation and for patients with colorectal cancer cachexia.

BACKGROUND: The development and progression of cancer cachexia are connected to systemic inflammation and physical performance. However, few relevant studies have reported the survival outcomes prediction of systemic inflammation and physical performance in patients with colorectal cancer (CRC) cachexia. This study investigated the prognostic prediction value of systemic inflammation and performance status in patients with CRC cachexia. METHODS: This multicentre cohort study prospectively collected 905 patients with CRC (58.3% males, 59.3 ± 11.5 years old). Cancer cachexia was diagnosed according to the 2011 Fearon Cachexia Diagnostic Consensus. The prognostic value of systematic inflammatory indicators was determined using the area under the curve, concordance index, and multivariate survival analysis. Performance status was evaluated with Eastern Coopertive Oncology Group performance score (ECOG-PS). Survival data were analysed using univariate and multivariate Cox regression analyses. RESULTS: The area under the curve, concordance index and survival analysis showed that C-reactive protein (CRP), lymphocyte to CRP ratio (LCR) and CRP to albumin ratio (CAR) were more stable and consistent with the survival of patients with CRC, both in non-cachexia and cachexia populations. Among patients with CRC cachexia, high inflammation [low LCR, hazard ratio (HR) 95% confidence interval (95% CI) = 3.33 (2.08-5.32); high CAR, HR (95% CI) = 2.92 (1.88-4.55); high CRP, HR (95% CI) = 3.12 (2.08-4.67)] indicated a worse prognosis, compared with non-cachexia patients [low LCR, HR (95% CI) = 2.28 (1.65-3.16); high CAR, HR (95% CI) = 2.36 (1.71-3.25); high CRP, HR (95% CI) = 2.58 (1.85-3.60)]. Similarly, among patients with CRC cachexia, high PS [ECOG-PS 2, HR (95% CI) = 1.61 (1.04-2.50); ECOG-PS 3/4, HR (95% CI) = 2.91 (1.69-5.00]) indicated a worse prognosis, compared with patients with CRC without cachexia [ECOG-PS 2, HR (95% CI) = 1.28 (0.90-1.81); ECOG-PS 3/4, HR (95% CI) = 2.41 (1.32-4.39]). Patients with CRC cachexia with an ECOG-PS score of 2 or 3-4 and a high inflammation had a shorter median survival time, compared with patients with an ECOG-PS score of 0/1 and a low inflammation. CONCLUSIONS: The systemic inflammatory markers LCR, CAR and CRP have stable prognostic values in patients with CRC. The ECOG-PS may be an independent risk factor for CRC. Combined evaluation of systemic inflammation and ECOG-PS in patients with CRC cachexia could provide a simple survival prediction.

Improving the assessment of malnutrition in cancer: Using systemic inflammation markers as a supplement to the inflammation items of the GLIM criteria.

BACKGROUND & AIMS: Systemic inflammation is a key pathogenic criterion for diagnosing malnutrition using the Global Leadership Initiative on Malnutrition (GLIM) criteria. Although cancer is commonly considered as a chronic inflammation-related disease, the inflammatory burden may vary depending on the type and stage of cancer. Therefore, a more precise definition of inflammation criteria could facilitate the identification of malnutrition in cancer. METHODS: This prospective multicenter study included 1683 cancer patients screened via NRS2002 for malnutrition risk. The inflammatory burden index (IBI), C-reactive protein (CRP) level, neutrophil-to-lymphocyte ratio (NLR), and albumin (ALB) level were used to assess the inflammatory burden. Kaplan-Meier and Cox regression analyses were used to determine the relationship between the GLIM criteria and overall survival. Harrell's concordance index (C-index) was used to compare the discriminative performance of the original, IBI-based, CRP-based, NLR-based, and ALB-based GLIM criteria for survival. Logistic regression models were used to assess the association between GLIM criteria and short-term outcomes, length of hospital stay, and hospitalization costs. RESULTS: Compared to the original GLIM criteria, the IBI/CRP/NLR/ALB-based GLIM criteria better predicted the long-term outcomes of patients with cancer (chi-square: 1.316 vs. 78.321 vs. 74.740 vs. 88.719 vs. 100.921). The C-index revealed that the inflammation marker-based GLIM criteria showed significantly better prognostic accuracy than the original GLIM criteria. The ALB-based GLIM criteria exhibited the best prognostic accuracy. The inflammation marker-based GLIM criteria were independent predictive factors for the long-term prognosis of cancer. Patients with malnutrition had a 45% higher risk of adverse long-term prognoses than those without malnutrition. The inflammation marker-based GLIM criteria had good prognostic ability to predict outcomes at 3, 6, and 12 months. The stepwise effect of the grading of severity via the IBI-based GLIM criteria and CRP-based GLIM criteria was notable. The inflammation marker-based GLIM criteria are useful for predicting short-term outcomes, length of hospitalization, and hospitalization costs. CONCLUSION: The inflammation marker-based GLIM criteria have a stronger predictive value than the original GLIM criteria in evaluating both the short- and long-term prognoses of cancer patients. It is recommended to use the inflammation marker-based GLIM criteria for nutritional evaluation of cancer patients.

De novo Creation and Assessment of a Prognostic Fat-Age-Inflammation Index "FAIN" in Patients With Cancer: A Multicenter Cohort Study.

Background and Aims: Malnutrition is highly prevalent and is related to multiple impaired clinical outcomes in cancer patients. This study aimed to de novo create an objective, nutrition-related index specially for prognostic purposes in oncology populations. Methods: We performed a multicenter cohort study including 14,134 cancer patients. The prognostic impact for each baseline characteristic was estimated by calculating Harrell's C-index. The optimal parameters reflecting the nutritional and inflammatory impact on patients' overall survival were selected to develop the fat-age-inflammation (FAIN) index. The associations of the FAIN with the nutritional status, physical performance, quality of life, short-term outcomes and mortality of patients were comprehensively evaluated. Independent external validation was performed to further assess the prognostic value of the FAIN. Results: The study enrolled 7,468 men and 6,666 women with a median age of 57 years and a median follow-up of 42 months. The FAIN index was defined as: (triceps skinfold thickness + albumin) / [age + 5 × (neutrophil count/lymphocyte count)]. There were significant associations of the FAIN with the nutritional status, physical performance, quality of life and short-term outcomes. The FAIN also showed better discrimination performance than the Nutritional Risk Index, the Prognostic Nutritional Index and the Controlling Nutritional Status index (all P < 0.05). In multivariable-adjusted models, the FAIN was independently associated with a reduced death hazard both as a continuous variable (HR = 0.57, 95%CI = 0.47-0.68) and per one standard deviation (HR = 0.83, 95%CI = 0.78-0.88). External validation in a multicenter lung cancer cohort (n = 227) further confirmed the prognostic value of the FAIN. Conclusions: This study created and assessed the prognostic FAIN index, which might act as a feasible option to monitor the nutritional status and help develop intervention strategies to optimize the survival outcomes of cancer patients.

Several anthropometric measurements and cancer mortality: predictor screening, threshold determination, and joint analysis in a multicenter cohort of 12138 adults.

BACKGROUND: Anthropometric measurements (AMs) are cost-effective surrogates for evaluating body size. This study aimed to identify the optimal prognostic AMs, their thresholds, and their joint associations with cancer mortality. METHODS: We performed an observational cohort study including 12138 patients with cancer at five institutions in China. Information on demographics, disease, nutritional status, and AMs, including the body mass index, mid-arm muscle circumference, mid-arm circumference, handgrip strength, calf circumference (CC), and triceps-skinfold thickness (TSF), was collected and screened as mortality predictors. The optimal stratification was used to determine the thresholds to categorize those prognostic AMs, and their associations with mortality were estimated independently and jointly by calculating multivariable-adjusted hazard ratios (HRs). RESULTS: The study included 5744 females and 6394 males with a mean age of 56.9 years. The CC and TSF were identified as better mortality predictors than other AMs. The optimal thresholds were women 30 cm and men 32.8 cm for the CC, and women 21.8 mm and men 13.6 mm for the TSF. Patients in the low CC or low TSF group had a 13% (HR = 1.13, 95% CI = 1.03-1.23) and 22% (HR = 1.22, 95% CI = 1.12-1.32) greater mortality risk compared with their normal CC/TSF counterparties, respectively. Concurrent low CC and low TSF showed potential joint effect on mortality risk (HR = 1.39, 95% CI = 1.25-1.55). CONCLUSIONS: These findings support the importance of assessing the CC and TSF simultaneously in hospitalized cancer patients to guide interventions to optimize their long-term outcomes.

Ectopic bronchogenic cyst in the retroperitoneal region: a case report and literature review of adult patients.

BACKGROUND: Bronchogenic cyst is congenital aberration of bronchopulmonary malformation, which is rarely encountered in the abdomen and retroperitoneum. We present a case report and literature review of retroperitoneal bronchogenic cyst. CASE PRESENTATION: A 53-year-old female presented to outpatient clinic for a routine checkup of lumbar intervertebral disc herniation. She received a contrast computed tomography scan of the abdomen which revealed a retroperitoneal cystic lesion below the left crura of diaphragm. Afterward, the patient underwent a laparoscopic excision of the cystic lesion and was discharged uneventfully at postoperative day 4. Histopathological findings confirmed the diagnosis of retroperitoneal bronchogenic cyst. Our literature review identified 55 adult cases in recent two decades. The average age at diagnosis was 43.2 (range 17-69) years. 44 (80%) cases had a retroperitoneal cyst on the left side, and 52 (94.5%) cases underwent curative excision through open or laparoscopic surgery. In the available follow up of cases, there was no recurrence after surgery. CONCLUSIONS: Bronchogenic cyst is rare in the retroperitoneal region. It should be considered as one of the differential diagnoses of a retroperitoneal neoplasm.

Identification of Candidate Biomarkers and Prognostic Analysis in Colorectal Cancer Liver Metastases.

BACKGROUND: Colorectal cancer (CRC), one of the most common malignant tumors worldwide, has a high mortality rate, especially for patients with CRC liver metastasis (CLM). However, CLM pathogenesis remains unclear. METHODS: We integrated multiple cohort datasets and databases to clarify and verify potential key candidate biomarkers and signal transduction pathways in CLM. GEO2R, DAVID 6.8, ImageGP, STRING, UALCAN, ONCOMINE, THE HUMAN PROTEIN ATLAS, GEPIA 2.0, cBioPortal, TIMER 2.0, DRUGSURV, CRN, GSEA 4.0.3, FUNRICH 3.1.3 and R 4.0.3 were utilized in this study. RESULTS: Sixty-three pairs of matched colorectal primary cancer and liver metastatic gene expression profiles were screened from three gene expression profiles (GSE6988, GSE14297 and GSE81558). Thirty-one up-regulated genes and four down-regulated genes were identified from these three gene expression profiles and verified by another gene expression profiles (GSE 49355) and TCGA database. Two pathways (IGFBP-IGF signaling pathway and complement-coagulation cascade), eighteen key differentially expressed genes (DEGs), six hub genes (SPARCL1, CDH2, CP, HP, TF and SERPINA5) and two biomarkers (CDH2 and SPARCL1) with significantly prognostic values were screened by multi-omics data analysis and verified by Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) cohort. CONCLUSIONS: In this study, we identified a robust set of potential candidate biomarkers in CLM, which would provide potential value for early diagnosis and prognosis, and would promote molecular targeting therapy for CRC and CLM.

A fusion decision system to identify and grade malnutrition in cancer patients: Machine learning reveals feasible workflow from representative real-world data.

BACKGROUND AND AIMS: Most nutritional assessment tools are based on pre-defined questionnaires or consensus guidelines. However, it has been postulated that population data can be used directly to develop a solution for assessing malnutrition. This study established a machine learning (ML)-based, individualized decision system to identify and grade malnutrition using large-scale data from cancer patients. METHODS: This was an observational, nationwide, multicenter cohort study that included 14134 cancer patients from five institutions in four different geographic regions of China. Multi-stage K-means clustering was performed to isolate and grade malnutrition based on 17 core nutritional features. The effectiveness of the identified clusters for reflecting clinical characteristics, nutritional status and patient outcomes was comprehensively evaluated. The study population was randomly split for model derivation and validation. Multiple ML algorithms were developed, validated and compared to screen for optimal models to implement the cluster prediction. RESULTS: A well-nourished cluster (n = 8193, 58.0%) and a malnourished cluster with three phenotype-specific severity levels (mild = 2195, 15.5%; moderate = 2491, 17.6%; severe = 1255, 8.9%) were identified. The clusters showed moderate agreement with the Patient-Generated Subjective Global Assessment and the Global Leadership Initiative on Malnutrition criteria. The severity of malnutrition was negatively associated with the nutritional status, physical status, quality of life, and short-term outcomes, and was monotonically correlated with reduced overall survival. A multinomial logistic regression was found to be the optimal ML algorithm, and models built based on this algorithm showed almost perfect performance to predict the clusters in the validation data. CONCLUSIONS: This study developed a fusion decision system that can be used to facilitate the identification and severity grading of malnutrition in patients with cancer. Moreover, the study workflow is flexible, and might provide a generalizable solution for the artificial intelligence-based assessment of malnutrition in a wider variety of scenarios.

Adsorption and inhibition behavior of imidazolium tetrafluoroborate derivatives as green corrosion inhibitors for carbon steel.

The adsorption and inhibition mechanism of chain length increase and group substitution of imidazole tetrafluoroborate derivatives for the corrosion inhibition of carbon steel in HCl solution was revealed in detail via the density functional theory, molecular dynamics (MD) simulation, and quantitative structure-activity relationship (QSAR) methods. The main reactive site of an ionic liquid is located on its imidazolium ring. With alkyl chain lengthening or the introduction of methyl groups onto the imidazolium ring, its molecular reactivity and electron-donating ability increase the interaction between the ionic liquid and the Fe (110) surface. Therefore, the imidazolium rings of four IL inhibitors are more likely to lie on the Fe (110) surface in parallel through chemical adsorption. The interactions between N atoms in ionic liquids and the Fe (110) surface are stronger than those between the C atoms on the imidazolium rings of the four ionic liquid, and coordination bonds can be formed between N atoms and the Fe (110) surface. Therefore, ionic liquids can hinder the interaction between corrosion particles and the Fe (110) surface, hinder the diffusion of corrosion particles, and effectively reduce the number density of corrosion particles on the Fe (110) surface. A methyl substituent on the C2 atom of the imidazolium ring can enhance the electron-donating ability and adsorption tendency much more than an increase in the alkyl chain on the N3 atom. The four inhibitors are ordered in terms of corrosion inhibition efficiency as [C12DMIM]BF4 > [C10DMIM]BF4 > [C12MIM]BF4 > [C10MIM]BF4, which agrees well with the experimental results. A good correlation between experimental inhibition efficiency, concentration and microscopic structures parameters of ILs such as energy gap ΔE, polarizability P, electronegativity χ, hardness η, softness σ, number of electrons transferred ΔN, and electrophilicity ω was achieved.

Comparison of the AWGS and optimal stratification-defined handgrip strength thresholds for predicting survival in patients with lung cancer.

OBJECTIVES: Handgrip strength (HGS) is related to cancer mortality. The aim of this study was to compare the performance of the Asian Working Group for Sarcopenia 2019 (AWGS)- and optimal stratification (OS)-defined HGS thresholds for predicting the survival of patients with lung cancer (LC). METHODS: We performed an observational cohort study including 3230 patients with LC admitted to five institutions in China from November 2011 to January 2019. Comprehensive baseline and follow-up information was documented. Sex-specific thresholds for identifying patients with a low HGS were defined based on the AWGS (<28 kg in men and <18 kg in women) and the OS. The associations of a low HGS with survival were estimated by calculating multivariable-adjusted hazard ratios (HRs), and the relationships were flexibly modeled using restricted cubic splines. RESULTS: The study included 1041 women and 2189 men with a mean age of 60 y and a median follow-up time of 761 d. The OS-calculated HGS thresholds were <31.2 kg in men and <22.4 kg in women. There were significant associations between a low HGS defined by the AWGS (n = 1392; 43.1%) or the OS (n = 2034; 63%) and various nutritional characteristics. An AWGS-defined low HGS was associated with prolonged hospitalization. The OS-defined low HGS group was associated with a 23% greater death hazard than the normal HGS group (HR, 1.23; 95% confidence interval, 1.08-1.40). An n-shaped non-linear association was observed between the HGS and survival in women (P = 0.003). CONCLUSIONS: The OS-defined HGS thresholds show better performance than the AWGS for predicting the survival of patients with LC. Additionally, the HGS had n-shaped associations with the overall mortality among female patients with LC.

The GLIM criteria as an effective tool for nutrition assessment and survival prediction in older adult cancer patients.

BACKGROUND & AIMS: Elderly cancer patients are at particularly high risk for malnutrition because both the disease and the old age threaten their nutritional status. The Global Leadership Initiative on Malnutrition (GLIM) released new universal criteria for diagnosing and grading malnutrition, but the validation of these criteria in elderly cancer population is not well documented. Our objective was to investigate the application of the GLIM criteria in nutrition assessment and survival prediction in elderly cancer patients. METHODS: This retrospective cohort analysis was conducted on a primary cohort of 1192 cancer patients aged 65 years or older enrolled from a multi-institutional registry, and a validation cohort of 300 elderly cancer patients treated at the First Affiliated Hospital of Sun Yat-sen University. Patients considered at-risk for malnutrition based on the NRS-2002 were assessed using the GLIM criteria. The association between the nutritional status and patients' overall survival (OS) was then analyzed by the Kaplan-Meier method and a Cox model. A nomogram was also established that included additional independent clinical prognostic variables. To determine the predictive accuracy and discriminatory capacity of the nomogram, the C-index, receiver operating characteristic (ROC) curve and calibration curve were evaluated. RESULTS: The percentage of patients considered "at-risk" for malnutrition was 64.8% and 67.3% for the primary and validation cohorts, respectively. GLIM-defined malnutrition was diagnosed in 48.4% of patients in the primary cohort and 46.0% in the validation cohort. In the primary cohort, patients at risk of malnutrition (NRS-2002 ≥ 3) showed a worse OS than those with a NRS-2002 < 3 (HR 1.34, 1.10-1.64; p = 0.003). Additionally, patients with GLIM-defined severe malnutrition (HR1.71, 1.37-2.14; p < 0.001) or moderate malnutrition (HR1.35, 1.09-1.66; p = 0.006) showed a significantly shorter OS compared to those without malnutrition. The nomogram incorporating the domains of the GLIM with other variables was accurate, especially for predicting the 1- and 2-year overall survival rates. CONCLUSIONS: The GLIM criteria can be used in elderly cancer patients not only to assess malnutrition, but also to predict survival outcome. The nomogram developed based on the GLIM domains can provide a more accurate prediction of the prognosis than existing systems.

Complement C3 overexpression activates JAK2/STAT3 pathway and correlates with gastric cancer progression.

BACKGROUND: Localized C3 deposition is a well-known factor of inflammation. However, its role in oncoprogression of gastric cancer (GC) remains obscured. This study aims to explore the prognostic value of C3 deposition and to elucidate the mechanism of C3-related oncoprogression for GC. METHODS: From August to December 2013, 106 GC patients were prospectively included. The regional expression of C3 and other effectors in gastric tissues were detected by WB, IHC, qRT-PCR and other tests. The correlation of localized C3 deposition and oncologic outcomes was determined by 5-year survival significance. Human GC and normal epithelial cell lines were employed to detect a relationship between C3 and STAT3 signaling pathway in vitro experiments. RESULTS: C3 and C3a expression were markedly enhanced in GC tissues at both mRNA and protein levels compared with those in paired nontumorous tissues. According to IHC C3 score, 65 (61.3%) and 41 (38.7%) patients had high and low C3 deposition, respectively. C3 deposition was negatively correlated with plasma levels of C3 and C3a (both P < 0.001) and positively correlated with pathological T and TNM stages (both P < 0.001). High C3 deposition was identified as an independent prognostic factor of poor 5-year overall survival (P = 0.045). In vitro C3 administration remarkably enhanced p-JAK2/p-STAT3 expression in GC cell lines but caused a reduction of such activation when pre-incubated with a C3 blocker. Importantly, C3 failed to activate such signaling in cells pre-treated with a JAK2 inhibitor. CONCLUSIONS: Localized C3 deposition in the tumor microenvironment is a relevant immune signature for predicting prognosis of GC. It may aberrantly activate JAK2/STAT3 pathway allowing oncoprogression. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02425930, Registered 1st August 2013.

The mTORC1 signaling modulated by intracellular C3 activation in Paneth cells promotes intestinal epithelial regeneration during acute injury.

Complement activation is associated with regional inflammation during acute gastrointestinal injury (AGI). This study is designed to explore how intracellular C3 activation in Paneth cells (PCs) affects regeneration of intestinal epithelium during AGI. AGI was induced in wildtype C57BL/6 mice, with sham operation employed as control. Exogenous C3 (1 mg, I.P.) was applied at 6 h post-surgery. Intestinal crypts harvested from ileum were cultured with presence or absence of C3 (20 µg/ml), with small interfering RNA against BST1 and complement activation inhibitor selectively applied in vitro. The intestinal integrity, percentage of PCs and intestinal stem cells (ISCs) were evaluated. Importantly, cADPR, C3 fragments, and S6-related proteins were detected in PCs to inspect the mammalian target of rapamycin complex 1 (mTORC1) signaling. AGI caused breakdown of intestinal mucosa integrity and regional inflammation. Exogenous C3 by itself failed to promote the growth of intestinal epithelium, but distinctly enhanced the activity of PCs via intracellular activation, which subsequently supported the expansion of ISCs inside of intestinal crypts. Inhibition of C3 activation was associated with decreased expressions of S6, S6K1 and cADPR, with blocking BST1 found to depress cADPR only. Collectively, these data confirmed intracellular activation of C3 in PCs enhanced expansion of ISCs in response to acute injury. The mTORC1 signaling pathway in PCs contributed to this crosstalk during exogenous C3 treatment.

Deregulation of MicroRNA-375 Inhibits Proliferation and Migration in Gastric Cancer in Association With Autophagy-Mediated AKT/mTOR Signaling Pathways.

Gastric cancer is a deadly disease. Some microRNAs are involved in tumor invasion and metastasis. Underexpression of miR-375 has been correlated with tumorigenesis, treatment resistance, and poor prognosis. In this study, we first analyzed the profiles and prognostic values of miR-375 expression in gastric cancer tissues from a public database, and the expression level of miR-375 in gastric cancer samples and gastric cancer cell lines was then analyzed by quantitative real- time polymerase chain reaction. Significant underexpression of miR-375 was seen in all the gastric cancer samples compared to paired paracarcinoma tissues, and the expression level of miR-375 in the gastric cancer cell lines was negatively associated with the cell migration ability. A Cell proliferation (CCK-8) assay was performed to examine cell viability. Overexpression of miR-375 suppressed the proliferation of gastric cancer cells. A Western blot analysis was carried out to test protein expression. Overexpression of miR-375 inhibited autophagy through the AKT/ mammalian target of rapamycin signaling pathway. MiR-375 regulated invasion and migration via AKT/ mammalian target of rapamycin pathway-mediated epithelial-to-mesenchymal transition. Wound healing and migration assays were used to determine the motility of gastric cancer cells. A gastric cancer xenograft nude mouse model was used for an in vivo efficacy evaluation. Overexpression of miR-375 significantly suppressed cell proliferation in the established gastric cancer xenograft nude mouse model. Our results demonstrate that increasing the expression level of miR-375 suppresses proliferation in vitro and in vivo, and they provide a mechanistic and applicable rationale for the future clinical evaluation of miR-375 in gastric cancer treatment. Our findings provide not only new information about the molecular mechanism of microRNAs in regulating invasion and migration in gastric cancer but also a theoretical principle for a potential targeted therapy for gastric cancer.

Identification of key candidate genes, pathways and related prognostic values in ER-negative/HER2-negative breast cancer by bioinformatics analysis.

PURPOSE: Breast cancer possesses different molecular expressions and biological behaviors. The purpose of this study was to identify the key genes, pathways, and related prognostic values in estrogen receptor (ER)-negative/human epidermal growth factor 2 (HER2)-negative breast cancer by bioinformatics analysis. METHODS: The mRNA expression profiles of GSE20194 and GSE23988 were obtained from the Gene Expression Omnibus (GEO) database. Differently expressed genes (DEGs) were analyzed by GEO2R. A functional and pathway enrichment analysis of DEGs was conducted using DAVID. A protein-protein interaction (PPI) network was constructed using STRING and a module analysis of the PPI network was conducted using Cytoscape software. Survival analysis of hub genes was analyzed using the Kaplan-Meier plotter online tool. RESULTS: 108 ER-negative/HER2-negative and 172 ER-positive/HER2-negative breast cancer samples were collected from the datasets GSE20194 and GSE23988. A total of 355 DEGs were identified in the ER-negative/HER2-negative samples, including 140 up-regulated and 215 down-regulated genes. The PPI network of DEGs consisted of 265 nodes and 648 edges. A significant module (12 nodes and 56 edges) was acquired from the PPI network of DEGs. Geneontology (GO) and pathway enrichment analysis demonstrated that this module was mainly related with transcription, cell proliferation, binding, and pathways in the PI3K-Akt signaling pathway. The high expression of CCNE1, KRT16, and MYBL2 was associated with worse relapse-free survival (RFS) and overall survival (OS) in ER-negative/HER2-negative breast cancer. CONCLUSIONS: An integrated bioinformatics analysis was utilized to discover key candidate genes and pathways in ER-negative/HER2-negative breast cancer. This can improve the understanding of molecular mechanisms and provide potential candidate genes for diagnosis, prognosis, and individualized therapy.

Overexpression of RECQL4 is associated with poor prognosis in patients with gastric cancer.

The present study aimed to investigate the expression, clinical association, and prognosis of RecQ protein-like 4 (RECQL4) protein in human gastric cancers (GCs). The expression levels and prognostic value of RECQL4 were initially predicted by using bioinformatics. GC specimens and matched normal gastric tissues were evaluated by immunohistochemistry (IHC), and patient clinicopathological parameters and survival times were analyzed. Multivariate Cox analysis was used to determine the prognostic role of RECQL4 expression. The Oncomine database predicted that RECQL4 mRNA expression levels were significantly increased in GCs as compared with those in normal gastric tissues (P<0.05) and that patients with increased RECQL4 mRNA expression levels had significantly lower overall survival (OS) (P<0.001). The results of IHC showed that the positive rate of RECQL4 in the GC samples was significantly higher than that in the normal gastric mucosa specimens (P<0.05). RECQL4 expression was positively associated with depth of invasion and TNM (P<0.05). High RECQL4 expression in GC samples was significantly associated with poor OS (P=0.024). Positive RECQL4 expression, depth of invasion, lymphatic invasion, and TNM staging were independent factors for predicting worse OS rates by using multivariate analysis. Compared with expression levels in normal gastric tissues, RECQL4 was significantly overexpressed in GC samples, and increased RECQL4 expression was an independent predictor of poor prognosis in GC patients.

Determinants and nutritional assessment value of hand grip strength in patients hospitalized with cancer.

BACKGROUND AND OBJECTIVES: Hand grip strength (HGS) has emerged as a predictor of the nutritional status. However, many factors may modify the malnutrition-HGS association. This study explored the nutritional assessment value and determinants of HGS in patients hospitalized with cancer. METHODS AND STUDY DESIGN: In this multicenter, retrospective, observational study (11,314 patients), the Receiver operator characteristic curve was used to observe HGS and nutritional status sensitivity/specificity. Sex; age; height; weight; mid-upper arm circumference (MAMC); Patient-Generated Subjective Global Assessment (PG-SGA) score; Karnofsky score; physical function (PF) domain; cognitive function (CF) domain; global health and quality of life (QL) domain of EORTC QLQ-C30 (a quality of life instrument designed by the European Organization for Research and Treatment of Cancer); and albumin, prealbumin, and hemoglobin levels were included in a Stepwise analysis model to identify the factors influencing HGS. RESULTS: HGS showed a very low diagnostic value and accuracy for identifying severe malnourishment (area under the curve, 0.615-0.640; p<0.01). HGS positively correlated with sex; height; weight; MAMC; Karnofsky score; QL, PF, and CF domains; and hemoglobin and prealbumin levels (Beta= 0.02-0.42, p<=0.05), and negatively with age (Beta=-0.19, p<0.01). However, the PG-SGA score was excluded because of its very limited contribution to HGS variability. CONCLUSIONS: HGS is a mutifactorial index. The use of HGS cutoff values to identify malnutrition is markedly challenging. Thus, HGS may be of limited use as a predictor of nutritional status.

[Observation of the efficacy of biological patch in hybrid technique for incisional herniorrhaphy: 5-year follow-up results from a single center].

OBJECTIVE: To observe the safety and efficacy of biological patch (Biodesign Surgisis mesh, SIS) in hybrid technique for incisional herniorrhaphy. METHODS: Clinical and follow-up data of 14 incisional hernia patients who underwent incisional herniorrhaphy with hybrid technique, using porcine small intestinal submucosa acellular matrix patch, at the First Affiliated Hospital of Sun Yat-sen University from January 1, 2012 to June 31, 2016 were analyzed retrospectively. This Biodesign Surgisis patch for incisional hernia is produced by the Cook company in the United States. The size of patch ranged from 9 cm × 15 cm to 20 cm × 25 cm. During operation, according to abdominal wall defect, the patch was cut to ensure the distance from its edge to the border of abdominal wall defect more than 5 cm. RESULTS: There were four male and tenfemale patients with average age of (67.7±11.6) years and average body mass index(BMI) of (25.5±1.7) kg/m². As for operative history of these 14 cases, 7 cases had gastrointestinal tumor surgery, 2 had appendectomy, 1 had upper abdominal white line hernia repair, 1 had hysterectomy, 1 had cholecystectomy, 1 had splenectomy plus portal vein dissection, and 1 had right kidney and right ureter total resection plus partial excision of bladder wall. Ten casesdeveloped incisional infection after previous surgery. The duration of incisional hernia ranged 1 to 180 months (median, 8 months). Two cases were refractory hernia, 1 was incarcerated hernia, and 11 were reversible hernia. The locations of incisional hernia included 4 cases of right ventral wall, 1 case of left ventral wall, 2 cases of supra-umbilical incision, 4 cases of infra-umbilical midline incision, and 3 cases of peri-umbilical midline incision. There were 3 cases of middle incisional hernia, 5 cases of large incisional hernia and 6 cases of huge incisional hernia. All the patients completed operations eventlessly. The average operative time was (202.5±72.9) minutes. The average length and width of hernia ring were (10.9±4.3) cm and (9.3±3.9) cm, respectively. Clean operation was performed in 11 cases, potential contaminative operation in 2 cases and contaminative operation in 1 case. The amount of operative bleeding was (15.0±4.8) ml. The NRS pain scores within 24 hours after the operation, at POD3 and at POD7 were 5.1±0.9, 4.2±0.7 and 3.7±0.9, respectively. The time to flatus after operation was (2.5±0.9) days and the time to liquid diet was (3.8±1.2) days. No patient died during the perioperative period. The average hospitalization time was (21.5±12.0) days. Postoperative complications occurred in 8 cases, including 4 cases of fever, 8 cases of incision complications, 4 cases of abdominal infection, 4 cases of intestinal obstruction, 5 cases of effusion under patch, 2 cases of pneumonia, and 1 case of acute myocardial infarction. According to the Clavien-Dindo classification, 3 cases were grade zero, 3 cases were grade I(, 6 cases were grade II(, 1 case was grade III(, and 1 case was grade IIII(. Thirteen patients received follow-up and the average follow-up time was (33.2±12.3) (18.2-61.0) months. One patient died of cerebral infarction 38 months after operation. The chronic abdominal pain or discomfort was found in 4 cases. The recurrent incisional hernia developed in 5 cases and the average time of recurrence was (11.0±8.3) months. CONCLUSIONS: Biological patch can be used safely and effectively in hybrid technique for incisional herniorrhaphy. However, the morbidity of postoperative complication and the risk of recurrence are high. Terefore, the long-term outcome is still subject to observation.

Elevated Expression of Kin17 in Cervical Cancer and Its Association With Cancer Cell Proliferation and Invasion.

BACKGROUND: Cervical cancer is one of the most common cancers in women worldwide. Emerging evidence suggests that kin17 is a tumor-promoting protein in some types of solid tumors. However, whether kin17 contributes to cervical cancer carcinogenesis remains unknown. METHODS: Kin17 expression in clinical samples from Guangdong Women and Children's Hospital and Health Institute was detected by immunohistochemical staining. A series of functional experiments including 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay, 5-bromo-2'-deoxyuridine assay, colony formation, transwell assay, flow cytometry of apoptosis, and cell cycle were performed to explore the roles of kin17 in cervical cancer cells HeLa. RESULTS: In this study, we showed for the first time that the expression of kin17 was significantly increased in clinical cervical cancer samples, and associated with tumor differentiation, lymph node metastasis, and ki-67 expression in a clinicopathologic characteristics review. Furthermore, silence of kin17 in HeLa cells inhibited cell proliferation, clone formation, cell cycle progression, migration, and invasion, and also promoted cell apoptosis. CONCLUSION: Our findings demonstrate that kin17 is closely related to the cell proliferation and invasion of cervical cancer and could be a novel diagnostic and therapeutic target for cervical cancer management. The underlying mechanisms should be elucidated in future research.

Up-regulation of CNDP2 facilitates the proliferation of colon cancer.

BACKGROUND: Cytosolic nonspecific dipetidase (CN2) belongs to the family of M20 metallopeptidases. It was stated in previous articles that higher expression levels of CN2 were observed in renal cell carcinoma and breast cancer. Our study explored the correlation between CN2 and colon carcinogenesis. METHODS: We analysed the relationship between 183 patients clinicopathological characteristics and its CN2 expression. To detect the levels of CN2 in colon cancer cell lines and colon cancer tissues by western blot. To verify cell proliferation in colon cancer cells with knockdown of CNDP2 and explore the causes of these phenomena. RESULTS: The expression levels of CN2 in clinical colon tumors and colon cancer cell lines were significantly higher than that in normal colon mucosa and colon cell lines. The difference in CN2 levels was associated with tumor location (right- and left-sided colon cancer), but there was no significant association with age, gender, tumor size, tumor grade, tumor stage or serum carcinoembryonic antigen (CEA). Knockdown of CNDP2 inhibited cell proliferation, blocked cell cycle progression and retarded carcinogenesis in an animal model. The signaling pathway through which knockdown of CNDP2 inhibited cell proliferation and tumorigenesis involved in EGFR, cyclin B1 and cyclin E. CONCLUSIONS: Knockdown of CNDP2 can inhibit the proliferation of colon cancer in vitro and retarded carcinogenesis in vivo.

KIN enhances stem cell-like properties to promote chemoresistance in colorectal carcinoma.

Chemotherapy is widely used in colorectal cancer (CRC) treatment, especially in advanced stage patients. However, it is inevitable to develop chemoresistance. Recently, cancer cells acquired stem cell-like properties or cancer stem cells (CSC) were proved to attribute to chemoresistance. Here, we found that KIN protein was elevated in CRC cell lines and tissue specimens as compared to normal controls. Upregulation of KIN positively correlates with the metastatic status of CRC patients. Patients with high KIN expression showed poor prognosis and were with a short survival time. Overexpression of KIN enhanced, while silencing KIN impaired, chemoresistance to oxaliplatin (Ox) or 5-fluorouracil (5-FU) in CRC cell lines. Further investigation demonstrated that overexpression of KIN rendered CRC cells enriching CSC markers and CSC phenotype, and silencing KIN reduced CSC markers and CSC phenotype. Our findings suggest that the KIN level may be a suitable marker for predicting chemotherapy response in CRC, and silencing KIN plus chemotherapy may be a novel therapy for CRC treatment.