Development and validation of a nomogram to predict cancer-specific survival of elderly patients with unresected gastric cancer who received chemotherapy.

This investigation aimed to explore the prognostic factors in elderly patients with unresected gastric cancer (GC) who have received chemotherapy and to develop a nomogram for predicting their cancer-specific survival (CSS). Elderly gastric cancer patients who have received chemotherapy but no surgery in the Surveillance, Epidemiology, and End Results Database between 2004 and 2015 were included in this study. Cox analyses were conducted to identify prognostic factors, leading to the formulation of a nomogram. The nomogram was validated using receiver operating characteristic (ROC) and calibration curves. The findings elucidated six prognostic factors encompassing grade, histology, M stage, radiotherapy, tumor size, and T stage, culminating in the development of a nomogram. The ROC curve indicated that the area under curve of the nomogram used to predict CSS for 3, 4, and 5 years in the training queue as 0.689, 0.708, and 0.731, and in the validation queue, as 0.666, 0.693, and 0.708. The calibration curve indicated a high degree of consistency between actual and predicted CSS for 3, 4, and 5 years. This nomogram created to predict the CSS of elderly patients with unresected GC who have received chemotherapy could significantly enhance treatment accuracy.

Spatial mapping of corneal biomechanical properties using wave-based optical coherence elastography.

Quantifying the mechanical properties of the cornea can provide valuable insights into the occurrence and progression of keratoconus, as well as the effectiveness of corneal crosslinking surgery. This study presents a non-contact and non-invasive wave-based optical coherence elastography system that utilizes air-pulse stimulation to create a two-dimensional map of corneal elasticity. Homogeneous and dual concentration phantoms were measured with the sampling of 25 × 25 points over a 6.6 × 6.6 mm2 area, to verify the measurement capability for elastic mapping and the spatial resolution (0.91 mm). The velocity of elastic waves distribution of porcine corneas before and after corneal crosslinking surgery were further mapped, showing a significant change in biomechanics in crosslinked region. This system features non-invasiveness and high resolution, holding great potential for application in ophthalmic clinics.

Single-cell multi-omics sequencing reveals chromosome copy number inconsistency between trophectoderm and inner cell mass in human reconstituted embryos after spindle transfer.

STUDY QUESTION: Is the chromosome copy number of the trophectoderm (TE) of a human reconstituted embryos after spindle transfer (ST) representative of the inner cell mass (ICM)? SUMMARY ANSWER: Single-cell multi-omics sequencing revealed that ST blastocysts have a higher proportion of cell lineages exhibiting intermediate mosaicism than conventional ICSI blastocysts, and that the TE of ST blastocysts does not represent the chromosome copy number of ICM. WHAT IS KNOWN ALREADY: Preimplantation genetic testing for aneuploidy (PGT-A) assumes that TE biopsies are representative of the ICM, but the TE and ICM originate from different cell lineages, and concordance between TE and ICM is not well-studied, especially in ST embryos. STUDY DESIGN, SIZE, DURATION: We recruited 30 infertile women who received treatment at our clinic and obtained 45 usable blastocysts (22 from conventional ICSI and 23 reconstituted embryos after ST). We performed single-cell multi-omics sequencing on all blastocysts to predict and verify copy number variations (CNVs) in each cell. We determined the chromosome copy number of each embryo by analysing the proportion of abnormal cells in each blastocyst. We used the Bland-Altman concordance and the Kappa test to evaluate the concordance between TE and ICM in the both groups. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study was conducted at a public tertiary hospital in China, where all the embryo operations, including oocytes retrieval, ST, and ICSI, were performed in the embryo laboratory. We utilized single-cell multi-omics sequencing technology at the Biomedical Pioneering Innovation Center, School of Life Sciences, Peking University, to analyse the blastocysts. Transcriptome sequencing was used to predict the CNV of each cell through bioinformatics analysis, and the results were validated using the DNA methylation library of each cell to confirm chromosomal normalcy. We conducted statistical analysis and graphical plotting using R 4.2.1, SPSS 27, and GraphPad Prism 9.3. MAIN RESULTS AND THE ROLE OF CHANCE: Mean age of the volunteers, the blastocyst morphology, and the developmental ratewere similar in ST and ICSI groups. The blastocysts in the ST group had some additional chromosomal types that were prone to variations beyond those enriched in the blastocysts of the ICSI group. Finally, both Bland-Altman concordance test and kappa concordancetest showed good chromosomal concordance between TE and ICM in the ICSI blastocysts (kappa = 0.659, P < 0.05), but not in ST blastocysts (P = 1.000), suggesting that the TE in reconstituted embryos is not representative of ICM. Gene functional annotation (GO and KEGG analyses) suggests that there may be new or additional pathways for CNV generation in ST embryos compared to ICSI embryos. LIMITATIONS, REASONS FOR CAUTION: This study was mainly limited by the small sample size and the limitations of single-cell multi-omics sequencing technology. To select eligible single cells, some cells of the embryos were eliminated or not labelled, resulting in a loss of information about them. The findings of this study are innovative and exploratory. A larger sample size of human embryos (especially ST embryos) and more accurate molecular genetics techniques for detecting CNV in single cells are needed to validate our results. WIDER IMPLICATIONS OF THE FINDINGS: Our study justifies the routine clinical use of PGT-A in ICSI blastocysts, as we found that the TE is a good substitute for ICM in predicting chromosomal abnormalities. While PGT-A is not entirely accurate, our data demonstrate good clinical feasibility. This trial was able to provide correct genetic counselling to patients regarding the reliability of PGT-A. Regarding ST blastocysts, the increased mosaicism rate and the inability of the TE to represent the chromosomal copy number of the ICM are both biological characteristics that differentiate them from ICSI blastocysts. Currently, ST is not used clinically on a large scale to produce blastocysts. However, if ST becomes more widely used in the future, our study will be the first to demonstrate that the use of PGT-A in ST blastocysts may not be as accurate as PGT-A for ICSI blastocysts. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by grants from the National Key R&D Program of China (2018YFA0107601) and the National Key R&D Program of China (2018YFC1003003). The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Nomogram for predicting occurrence and prognosis of liver metastasis in elderly colorectal cancer patients: a population-based study.

Introduction: This study aimed to explore independent risk and prognostic factors in elderly patients with colorectal cancer liver metastasis (ECRLM) and generate nomograms for predicting the occurrence and overall survival (OS) rates of such patients. Method: Elderly colorectal cancer patients (ECRC) from 2010 to 2015 in the Surveillance, Epidemiology, and End Results (SEER) database were included in this study. External validation relied on Chinese patients from the China-Japan Union Hospital of Jilin University. Univariate and multivariate logistic regression analyses were employed to identify liver metastasis (LM) risk variables, which were used to create a nomogram to estimate LM probabilities in patients with ECRC. Univariate and multivariable Cox analyses were performed to identify prognostic variables and further derive nomograms that could predict the OS of patients with ERCLM. Differences in lifespan were assessed using the Kaplan-Meier analysis. Finally, the quality of the nomograms was verified using decision curve analysis (DCA), calibration curves, and receiver operating characteristic curves (ROC). Result: In the SEER cohort, 32,330 patients were selected, of those, 3,012 (9.32%) were diagnosed with LM. A total of 188 ECRLM cases from a Chinese medical center were assigned for external validation. LM occurrence can be affected by 13 factors, including age at diagnosis, marital status, race, bone metastases, lung metastases, CEA level, tumor size, Grade, histology, primary site, T stage, N stage and sex. Furthermore, in ECRLM patients, 10 variables, including age at diagnosis, CEA level, tumor size, lung metastasis, bone metastasis, chemotherapy, surgery, N stage, grade, and race, have been shown to be independent prognostic predictors. The results from both internal and external validation revealed a high level of accuracy in predicting outcomes, as well as significant clinical utility, for the two nomograms. Conclusion: We created two nomograms to predict the occurrence and prognosis of LM in patients with ECRC, which would contribute significantly to the improvement in disease detection accuracy and the formulation of personalized cures for that particular demographic.

A predictive model for early death in elderly colorectal cancer patients: a population-based study.

Purpose: The purpose of this study is to determine what variables contribute to the early death of elderly colorectal cancer patients (ECRC) and to generate predictive nomograms for this population. Methods: This retrospective cohort analysis included elderly individuals (≥75 years old) diagnosed with colorectal cancer (CRC) from 2010-2015 in the Surveillance, Epidemiology, and End Result databases (SEER) databases. The external validation was conducted using a sample of the Chinese population obtained from the China-Japan Union Hospital of Jilin University. Logistic regression analyses were used to ascertain variables associated with early death and to develop nomograms. The nomograms were internally and externally validated with the help of the receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA). Results: The SEER cohort consisted of 28,111 individuals, while the Chinese cohort contained 315 cases. Logistic regression analyses shown that race, marital status, tumor size, Grade, T stage, N stage, M stage, brain metastasis, liver metastasis, bone metastasis, surgery, chemotherapy, and radiotherapy were independent prognostic factors for all-cause and cancer-specific early death in ECRC patients; The variable of sex was only related to an increased risk of all-cause early death, whereas the factor of insurance status was solely associated with an increased risk of cancer-specific early death. Subsequently, two nomograms were devised to estimate the likelihood of all-cause and cancer-specific early death among individuals with ECRC. The nomograms exhibited robust predictive accuracy for predicting early death of ECRC patients, as evidenced by both internal and external validation. Conclusion: We developed two easy-to-use nomograms to predicting the likelihood of early death in ECRC patients, which would contribute significantly to the improvement of clinical decision-making and the formulation of personalized treatment approaches for this particular population.

[Chemical composition analysis and value evaluation of stems and leaves of Astragalus membranaceus var. mongholicus].

This study aimed to provide data support for resource utilization of the stems and leaves of Astragalus membranaceus var. mongholicus(SLAM) by analyzing and evaluating the chemical constituents. The crude protein, crude fiber, and soluble saccharide of SLAM were analyzed by Kjeldahl method, filtration method, and UV-Vis spectrophotometry, respectively. The nucleosides, amino acids, flavonoids, and saponins of SLAM were analyzed by ultraperformance liquid chromatography-triple quadrupole mass spectrometry(UPLC-TQ-MS). Combined with principal component analysis(PCA), the quality difference of resource components of SLAM was comprehensively evaluated. The results showed that the average content of crude protein, crude fiber, total polysaccharide, and redu-cing sugar in SLAM was 5.11%, 30.33%, 11.03 mg·g~(-1), and 31.90 mg·g~(-1), respectively. Six nucleosides, 15 amino acids, 22 flavonoids, and one saponin were detected, with an average content of 1.49 mg·g~(-1), 6.00 mg·g~(-1), 1.86 mg·g~(-1), and 35.67 µg·g~(-1), respectively. The content of various types of chemical components in SLAM differed greatly in different harvesting periods and growing years. The results of PCA showed that the quality of SLAM produced in Ningxia was superior. The results can provide references for the utilization of SLAM.

Long-term music adjuvant therapy enhances the efficacy of sub-dose antiepileptic drugs in temporal lobe epilepsy.

AIMS: Noninvasive music adjuvant therapy shows great potential in improving seizure control when combined with routine antiepileptic drugs. However, the diversity of previous music protocols has resulted in disparate outcomes. The optimized protocol and features for music adjuvant therapy are still not fully understood which limits its feasibility. METHODS: By applying different regimens of music therapy in various temporal lobe epilepsy models, we evaluated the effect of music in combination with sub-dose drugs on epileptic seizures to determine the optimized protocol. RESULTS: A subgroup of kindled mice that were responsive to music adjuvant therapy was screened. In those mice, sub-dose drugs which were noneffective on kindled seizures, alleviated seizure severity after 12 h/day Mozart K.448 for 14 days. Shorter durations of music therapy (2 and 6 h/day) were ineffective. Furthermore, only full-length Mozart K.448, not its episodes or other music varieties, was capable of enhancing the efficacy of sub-dose drugs. This music therapeutic effect was not due to increasing cerebral drug concentration, but instead was related with the modulation of seizure electroencephalogram (EEG) spectral powers in the hippocampus. CONCLUSION: These results indicate that long-term full-length Mozart K.448 could enhance the anti-seizure efficacy of sub-dose drugs and may be a promising noninvasive adjuvant therapy for temporal lobe epilepsy.

Knockdown of OLR1 weakens glycolytic metabolism to repress colon cancer cell proliferation and chemoresistance by downregulating SULT2B1 via c-MYC.

Chemoresistance is one of the major problems of colon cancer treatment. In tumors, glycolytic metabolism has been identified to promote cell proliferation and chemoresistance. However, the molecular mechanisms underlying glycolytic metabolism and chemoresistance in colon cancer remains enigmatic. Hence, this research was designed to explore the mechanism underlying the OLR1/c-MYC/SULT2B1 axis in the regulation of glycolytic metabolism, to affect colon cancer cell proliferation and chemoresistance. Colon cancer tissues and LoVo cells were attained, where OLR1, c-MYC, and SULT2B1 expression was detected by immunohistochemistry, RT-qPCR, and western blot analysis. Next, ectopic expression and knockdown assays were implemented in LoVo cells. Cell proliferation was detected by MTS assay and clone formation. Extracellular acidification, glucose uptake, lactate production, ATP/ADP ratio, and GLUT1 and LDHA expression were measured to evaluate glycolytic metabolism. Then, the transfected cells were treated with chemotherapeutic agents to assess drug resistance by MTS experiments and P-gp and SMAD4 expression by RT-qPCR. A nude mouse model of colon cancer transplantation was constructed for in vivo verification. The levels of OLR1, c-MYC, and SULT2B1 were upregulated in colon cancer tissues and cells. Mechanistically, OLR1 increased c-MYC expression to upregulate SULT2B1 in colon cancer cells. Moreover, knockdown of OLR1, c-MYC, or SULT2B1 weakened glycolytic metabolism, proliferation, and chemoresistance of colon cancer cells. In vivo experiments authenticated that OLR1 knockdown repressed the tumorigenesis and chemoresistance in nude mice by downregulating c-MYC and SULT2B1. Conclusively, knockdown of OLR1 might diminish SULT2B1 expression by downregulating c-MYC, thereby restraining glycolytic metabolism to inhibit colon cancer cell proliferation and chemoresistance.

The mining and construction of a knowledge base for gene-disease association in mitochondrial diseases.

Mitochondrial diseases are a group of heterogeneous genetic metabolic diseases caused by mitochondrial DNA (mtDNA) or nuclear DNA (nDNA) gene mutations. Mining the gene-disease association of mitochondrial diseases is helpful for understanding the pathogenesis of mitochondrial diseases, for carrying out early clinical diagnosis for related diseases, and for formulating better treatment strategies for mitochondrial diseases. This project researched the relationship between genes and mitochondrial diseases, combined the Malacards, Genecards, and MITOMAP disease databases to mine the knowledge on mitochondrial diseases and genes, used database integration and the sequencing method of the phenolyzer tool to integrate disease-related genes from different databases, and sorted the disease-related candidate genes. Finally, we screened 531 mitochondrial related diseases, extracted 26,723 genes directly or indirectly related to mitochondria, collected 24,602 variant sites on 1474 genes, and established a mitochondrial disease knowledge base (MitDisease) with a core of genes, diseases, and variants. This knowledge base is helpful for clinicians who want to combine the results of gene testing for diagnosis, to understand the occurrence and development of mitochondrial diseases, and to develop corresponding treatment methods.

Metabolic Profiling of Urinary Chiral Amino-Containing Biomarkers for Gastric Cancer Using a Sensitive Chiral Chlorine-Labeled Probe by HPLC-MS/MS.

Screening of characteristic biomarkers from chiral amino-containing metabolites in biological samples is difficult and important for the noninvasive diagnosis of gastric cancer (GC). Here, an enantiomeric pair of chlorine-labeled probes d-BPCl and l-BPCl was synthesized to selectively label d- and l-amino-containing metabolites in biological samples, respectively. Incorrect structural annotations were excluded according to the characteristic 3:1 abundance ratio of natural chlorine isotopes (35Cl and 37Cl) derived from the probes. A sensitive C18 HPLC-QQQ-MS/MS method in combination with the probes was then developed and applied in metabolomic analysis of amino-containing metabolites in urine samples. A total of 161 amino-containing metabolites were rapidly separated and determined, and 28 chiral amino acids and achiral glycine were quantified with good precision and accuracy. A total of 18 differential variables were discriminated by analyzing chiral amino-containing metabolites in urine samples of the GC patient and healthy person using the probe-based HPLC-MS/MS-MRM method combined with the orthogonal partial least squares discriminant analysis and Mann-Whitney U test with false discovery rate correction for multiple hypotheses. A diagnostic regression model including d-isoleucine, d-serine, and ß-(pyrazol-1-yl)-l-alanine and age was then constructed with an average prediction correctness of 88.9% in the validation set. This work established a close connection between gastric cancer and chiral amino-containing metabolites. The mass spectrometry data analyzed in the study are publicly available via Mendeley Data (DOI: 10.17632/4bd93j9yrr.1).

Retracted: Transcription activation of microRNA-25 by PEA3 augments progression of gastric cancer through suppressing SIK1.

Retraction: Yu, W., Li, Q., Chen, T., Zhang, H., Cui, X. and Shen, K. (2021), Transcription activation of microRNA-25 by PEA3 augments progression of gastric cancer through suppressing SIK1. Exp Physiol. Accepted Author Manuscript. https://doi.org/10.1113/EP089254 The above article, published online in Experimental Physiology on April 20, 2021 in Wiley Online Library (https://physoc.onlinelibrary.wiley.com/doi/10.1113/EP089254) has been retracted by agreement between the journal's Editor-in Chief Mike Tipton, the Authors and John Wiley & Sons Ltd. The authors requested withdrawal after an additional review of the data in the article showed inaccuracies in the data and its analysis.

HER2 Overexpression and Mismatch Repair Deficiency are Correlated with Malignancy in Colorectal Cancer.

PURPOSE: This study was designed to investigate the correlation between the expression of human epidermal growth factor receptor 2 (HER2), mismatch repair (MMR), and clinicopathological parameters and serum tumor markers in a total of 522 resection samples materials from colorectal cancer (CRC) patients. These data were also used to determine the links between HER2 and MMR expression and prognosis. METHODS: We conducted a retrospective analysis of the clinical data from 522 CRC patients. Immunohistochemistry (IHC) was used to detect HER2 overexpression and MMR deficiency (dMMR) in tumor specimens which were then correlated with various clinicopathological parameters. Prognostic value for HER2 and MMR expression was then evaluated using the data from 105 CRC patients. RESULTS: HER2 overexpression was identified in 35.63% of the samples evaluated in this study, while the total dMMR rate was 12.64%. Expression of HER2 and several, MMR proteins (MLH1, MSH-2, MSH-6, and PMS-2) were then correlated with tumor location. HER2 overexpression is significantly associated with increased depth of tumor invasion, lymph node metastasis, distant metastases, pTNM staging, vascular invasion, nerve infiltration, and serum carcinoembryonic antigen (CEA) levels. HER2 overexpression and dMMR increased with advancing clinical stage. In addition, deficiencies in MLH1 and PMS2 correlated with HER2 overexpression. Finally, the prognostic evaluations revealed that HER2 overexpression was closely associated with poorer clinical outcomes. CONCLUSION: HER2 overexpression is significantly correlated with multiple clinicopathological parameters resulting in a poorer prognosis. Moreover, the prognosis of patients with HER2 overexpression was worse, confirming its significance during disease assessment. In clinical practice, clinicians should pay close attention to the HER2 profile of patients as they may require more extensive clinical intervention. In addition, deficiencies in MLH1, MSH-2, MSH-6, or PMS-2 correlate with tumor location, and MLH1 and PMS2 expression is associated with lymph node metastasis and pTNM stage, suggesting that these may be additional markers in CRC risk assessments.

Short-term outcomes of medium-low rectal cancer treated by taTME and experience of 22 cases.

BACKGROUND AND METHODS: Transanal total mesorectal excision (taTME) is a novel radical resection technique that may address the unsatisfactory functional and oncological outcomes of medium-low rectal cancers. Although its oncological safety remains unclear, taTME has demonstrable value in surgery, complications, and oncological outcomes. Here, we explore the short-term outcomes of rectal cancer after taTME and discuss the surgical experience. Twenty-two patients with medium-low rectal cancer who underwent taTME were retrospectively evaluated. Comprehensive demographic, oncological, and clinical data were analyzed and the perioperative state and postoperative follow-up were evaluated. RESULTS: Over a median follow-up period of 24.4 (4-36) months, local recurrence occurred in one patient at 6 months postsurgery. Fecal incontinence was the most common postoperative complication, and 3-6 months of pelvic-floor-rehabilitation training greatly improved  anal function CONCLUSIONS: taTME achieved satisfactory short-term outcomes in oncological complications and postoperative functions. Accurate intraoperative anatomical location, identification of the rectovesical fascia, and neuroprotection are critical. However, this procedure has a steep learning curve, and large samples and multicenter studies are required to substantiate its effectiveness. DISCUSSION: We retrospectively analyzed the oncological and functional prognosis of 22 patients with colorectal cancer undergoing taTME surgery and preliminarily concluded taTME can be regarded as a safe and feasible treatment.

Long Noncoding RNA SNHG22 Induces Cell Migration, Invasion, and Angiogenesis of Gastric Cancer Cells via microRNA-361-3p/HMGA1/Wnt/ß-Catenin Axis.

BACKGROUND: The correlation between long non-coding RNAs (lncRNAs) and gastric cancer (GC) has been indicated. As a newly found lncRNA, small nucleolar RNA host gene 22 (SNHG22) functions as an oncogene in ovarian carcinoma and breast cancer. However, its action has not been explored in GC. Herein, the purpose of the current research was to examine the influence of SNHG22 on GC development. METHODS: RT-qPCR was used to identify SNHG22 and microRNA-361-3p (miR-361-3p) in GC tissues and cells. Functional assays were implemented to measure changes on biological activities of GC cells under different transfections. Besides, after human umbilical vein endothelial cells (HUVECs) were co-cultured with supernatant of transfected GC cells, angiogenesis was assessed by tube formation assay in vitro. HMGA1 and ß-catenin expression were determined. Finally, mechanistic assays, including RNA pull-down assay and dual-luciferase reporter assay, were employed to assess relationships among SNHG22, miR-361-3p, and HMGA1. RESULTS: SNHG22 and HMGA1 were highly expressed but miR-361-3p was poorly expressed in GC tissues. Mechanistically, SNHG22 bound to miR-361-3p, and miR-361-3p targeted HMGA1 to disrupt the Wnt/ß-catenin pathway. Following SNHG22 or HMGA1 silencing or miR-361-3p upregulation, we observed a decline of proliferation, migration, and invasion of GC cells and HUVEC angiogenesis but acceleration of GC cell apoptosis and cell cycle arrest. CONCLUSION: Collectively, SNHG22 silencing possessed tumor-suppressing potentials in GC development via Wnt/ß-catenin pathway by binding to miR-361-3p and downregulating HMGA1, highlighting a new promising road for GC treatment development.

Identification of Transcription Factor/Gene Axis in Colon Cancer Using a Methylome Approach.

Colon cancer is one of the most commonly diagnosed cancers worldwide. Both environmental and molecular characters can influence its development. DNA methylation has been heralded as a promising marker for use in cancer prevention, diagnosis, and treatment. It has been shown to facilitate cancer progression through multiple mechanisms. Changes in DNA methylation can inhibit or promote the binding of transcription factors (TFs) and further disturb gene regulation. Detection of DNA methylation-mediated regulatory events in colon cancer are critical for mining novel biomarkers. Here, we explore the influence of CpG sites located at promoter regions of differentially expressed genes and identify methylation-gene relationships using expression-methylation quantitative trait loci. We find that promoter methylation sites mainly negatively regulate the corresponding genes. We also identify candidate TFs that can bind to these sites in a sequence-dependent manner. By integrating transcriptome and methylome profiles, we construct a TF-CpG-gene regulatory network for colon cancer, which is used to determine the roles of TFs and methylation in the transcription process. Finally, based on TF-CpG-gene relationships, we design a framework to evaluate patient prognosis, which shows that one TF-CpG-gene triplet is significantly associated with patient survival rate and represents a potential novel biomarker for use in colon cancer prognosis and treatment.

The prospect of serum and glucocorticoid-inducible kinase 1 (SGK1) in cancer therapy: a rising star.

Serum and glucocorticoid-inducible kinase 1 (SGK1) is an AGC kinase that has been reported to be involved in a variety of physiological and pathological processes. Recent evidence has accumulated that SGK1 acts as an essential Akt-independent mediator of phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathway in cancer. SGK1 is overexpressed in several tumors, including prostate cancer, colorectal carcinoma, glioblastoma, breast cancer, and endometrial cancer. The functions of SGK1 include regulating tumor growth, survival, metastasis, autophagy, immunoregulation, calcium (Ca2+) signaling, cancer stem cells, cell cycle, and therapeutic resistance. In this review, we introduce the pleiotropic role of SGK1 in the development and progression of tumors, summarize its downstream targets, and integrate the knowledge provided by preclinical studies that the prospect of SGK1 inhibition as a potential therapeutic approach.

Serum netrin-1 as a biomarker for colorectal cancer detection.

BACKGROUND: Recent evidence support that netrin-1 involves in colorectal carcinogenesis. OBJECTIVE: This study was to evaluate the performance of serum netrin-1 for detection of colorectal cancer (CRC) in both clinical/screening sets. METHODS: A total of 115 consecutive patients with CRC and matched healthy controls were included in Clinical Set. Fifty subjects with CRC, 50 subjects with advanced adenoma (AA), and 150 matched control participants free of neoplasia were included in Screening Set. RESULTS: In Clinical set, subjects with CRC presented higher levels of serum netrin-1 (513.9 ± 22.6 pg/mL) than controls (347.8 ± 20.3 pg/mL, p< 0.0001). Similar in Screening set, serum netrin-1 was higher in CRC (644.5 ± 37.0 pg/mL, both p< 0.0001), compared with controls (407.7 ± 14.8 pg/mL) and AA (416.5 ± 18.5 pg/mL). However, there was no difference between controls and AA (p= 0.752). Compared with the low netrin-1 group, the high group presented increased risk of CRC (Clinical set: OR = 4.300, p< 0.001; Screening set: OR = 7.731, p< 0.001). ROC curve of netrin-1 was developed to detect CRC (Clinical set: AUC 0.703; Screening set: AUC 0.759). CONCLUSIONS: It suggests netrin-1 as a potential biomarker for CRC detection.

Clinical significance and diagnostic value of serum NSE, CEA, CA19-9, CA125 and CA242 levels in colorectal cancer.

The present study investigated the value of combinations of five specific tumor biomarkers for the diagnosis of colorectal cancer (CRC): Neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), cancer antigen (CA)19-9, CA125 and CA242. Associations between these markers and clinicopathological characteristics (including the Tumor-Node-Metastasis stage) were also assessed. Serum levels of the 5 markers were compared between 358 patients with CRC and 298 healthy individuals (CRC and control group, respectively). The NSE concentration of the CRC group was significantly higher compared with the control. Furthermore, patients at clinical stage III+IV exhibited significantly higher NSE levels compared with those at stage I+II. The serum NSE level of N+ patients was significantly higher compared with the N- group, and the NSE level of M1 patients was significantly compared with the M0 group. NSE level was also significantly associated with tumor stage, lymph node metastasis, distant metastasis and hematochezia. The area under the receiver operating characteristic curve (AUC) for NSE in CRC was 0.766, which was significantly higher than that of the other four markers, which ranged from 0.560-0.682. The AUC of NSE, CEA, CA19-9, CA125, CA242 combined was significantly higher compared with any of the markers individually (range, 0.796-0.858). Therefore, serum NSE may be a good clinical tool for the auxiliary diagnosis of colorectal cancer. Besides, the combination of NSE, CEA, CA19-9, CA125 and CA242 was significantly more sensitive compared with NSE alone. Thus, the combined detection of the 5 tumor markers may be more useful for the diagnosis of CRC.

Correlation study between serum neuro-specific enolase and gastric and colorectal cancers.

This study investigated the diagnostic value of preoperative serum neuro-specific enolase (NSE) in gastric cancer (GC) and colorectal cancer (CRC), and the diagnostic viability of combined serum NSE, carcinoembryonic antigen (CEA), cancer antigen (CA)19-9, and CA242.Patients with GC and CRC, and a healthy control group (n = 666 and 266, respectively) were compared with regard to NSE, CEA, CA19-9, and CA242 serum levels. NSE was analyzed for associations with clinicopathological parameters. To estimate the diagnostic potential of NSE, a receiver operating characteristic curve was constructed and the area under the curve (AUCs) was calculated for different patient subgroups.The median serum NSE level of the tumor group (20.925 ng/mL) was significantly higher than that of the control (15.190 ng/mL). Serum NSE was associated with pathological tumor-node-metastasis staging, lymph node metastasis, distant metastasis, vascular invasion, and nerve infiltration. The area under the receiver operating characteristic curve (AUC) for NSE in GC and CRC (0.769) was higher than for the other 3 markers (0.571-0.680). The AUC of the combined markers was higher than for any of the markers individually (0.778-0.810).The AUC for NSE alone suggests it may be an independent tumor marker, and useful for diagnosis of GC and CRC. However, the AUC for combined NSE, CEA, CA19-9, and CA242 was higher and thus potentially more diagnostic value.

Clinical significance of serum neuron-specific enolase in gastric adenocarcinoma.

As a biomarker, neuron-specific enolase (NSE) has been widely recognized in the diagnosis of benign diseases and malignant tumors. This study aimed to investigate the potential diagnostic value of NSE in patients with gastric adenocarcinoma.Serum levels of the NSE were compared between 219 patients with gastric adenocarcinoma and 298 healthy individuals, NSE and clinicopathological parameters were analyzed. Meanwhile, to evaluate the diagnostic capability of NSE, the receiver operating characteristic (ROC), and area under curve (AUC) was calculated.In the present study, the median serum NSE level of the patient group was 20.770 ng/mL, which was higher than that of the control group 15.625 ng/mL (P < .05). Serum NSE level in patients group compared with healthy control was statistically significant (P < .05). Serum NSE level was associated with pathological tumor-node-metastasis (pTNM) staging, lymph node metastasis, and distant metastasis in patients with gastric adenocarcinoma. Besides, the AUC of NSE in gastric adenocarcinoma was 0.742, which was higher than those of the other 3 markers (0.573-0.644). Besides, the AUC of the combined 4 markers was higher than any individual marker (0.778).Serum NSE detecting may have good value for diagnosis of gastric adenocarcinoma. Besides, the combination of NSE, CEA, CA19-9, and CA242 performed even better than any single marker. Thus, the combined detection of the 4 tumor markers may be more useful for the diagnosis of gastric adenocarcinoma.