The American Joint Committee on Cancer 8th classification states that colorectal cancer (CRC) is classified as N1c stage when regional lymph nodes (LNs) are negative and tumor deposits (TDs) are positive. However, how to classify TDs when regional LNs are positive remains unclear. The current study aimed to investigate the possibility of combining positive LNs and positive TDs to develop a modified pathological N (mpN) stage for CRC.

ETS transcription factor ELK3 (ELK3), a novel oncogene, affects pathological processes and progression of many cancers in human tissues. However, it remains unclear whether ELK3, as a key gene, affects the pathological process of gliomas and the prognosis of patients with gliomas. This study aimed to comprehensively and systematically reveal the correlation between ELK3 and the malignant progression of gliomas by analyzing clinical sample information stored in multiple databases. We revealed the putative mechanism of ELK3 involvement in malignant gliomas progression and identified a new and efficient biomarker for glioma diagnosis and targeted therapy. Based on the sample data from multiple databases and real-time quantitative polymerase chain reaction (RT-qPCR), the abnormally high expression of ELK3 in gliomas was confirmed. Kaplan-Meier and Cox regression analyses demonstrated that a high ELK3 expression was markedly associated with low patient survival and served as an independent biomarker of gliomas. Wilcox and Kruskal-Wallis tests revealed that expression of ELK3 was positively correlated with several clinical characteristics of patients with gliomas, such as age, WHO classification, and recurrence. Moreover, Cell Counting Kit-8 (CCK-8), immunofluorescence, and wound healing assays confirmed that ELK3 overexpression markedly promoted the proliferation and migration of glioma cells. Finally, gene set enrichment analysis (GSEA) and western blotting confirmed that overexpression of ELK3 regulated the JAK-STAT signaling pathway and upregulate the expression of signal transducer and activator of transcription 3 (STAT3) and phosphorylated STAT3 (P-STAT3) to promote the malignant transition of gliomas. Therefore, ELK3 may serve as an efficient biomarker for the diagnosis and prognosis of gliomas and it can also be used as a therapeutic target to improve the poor prognosis of patients with gliomas.

The long non-coding RNA LINC00467 plays a vital role in many malignancies. Nevertheless, the role of LINC00467 in prostate carcinoma (PC) is unknown. Herein, we aimed to explore the mechanism by which LINC00467 regulates PC progression.

This work explores the clinical significance of Delphian lymph nodes (DLN) in thyroid papillary carcinoma (PTC). At the same time, a nomogram is constructed based on clinical, pathological, and ultrasonic (US) features to evaluate the possibility of DLN metastasis (DLNM) in PTC patients. This is the first study to predict DLNM using US characteristics.

Colorectal cancer is the third most incidental cancer worldwide, and the response rate of current treatment for colorectal cancer is very low. Genome-scale metabolic models (GEMs) are systems biology platforms, and they had been used to assist researchers in understanding the metabolic alterations in different types of cancer. Here, we reconstructed a generic colorectal cancer GEM by merging 374 personalized GEMs from the Human Pathology Atlas and used it as a platform for systematic investigation of the difference between tumor and normal samples. The reconstructed model revealed the metabolic reprogramming in glutathione as well as the arginine and proline metabolism in response to tumor occurrence. In addition, six genes including ODC1, SMS, SRM, RRM2, SMOX, and SAT1 associated with arginine and proline metabolism were found to be key players in this metabolic alteration. We also investigated these genes in independent colorectal cancer patients and cell lines and found that many of these genes showed elevated level in colorectal cancer and exhibited adverse effect in patients. Therefore, these genes could be promising therapeutic targets for treatment of a specific colon cancer patient group.

Dysregulation of cytokines and growth factors is a general feature of tumor microenvironment, and unraveling the expression spectrum of cytokine and growth factor in niche is of utmost importance. Here, we evaluated cytokine profiling of bone marrow serum samples in AML patients and healthy controls. Protein expression profiling of serum from nine AML patients and five healthy controls was obtained using a biotinylated antibody chip. A total of 507 cytokines and growth factors were analyzed. Compared with healthy people, AML patients expressed 31 signature proteins, among which, 27 were significantly higher expressed and 4 proteins were lower. When patients were divided into favorable and poor prognosis, 12 signature proteins were significantly differentially expressed between these two groups. Furthermore, in order to identify the accuracy of cytokine expression profiles, we verified and analyzed the expression of THBS1 (Thrombospondin 1) in 116 patients and 9 healthy people. We found that THBS1 was lowly expressed in AML patients, which might be induced by promoter methylation, and patients with low THBS1 possessed shorter survivor time. Our data indicated that we successfully unveil differentially expressed proteins in AML patients using a biotinylated antibody chip; among them, THBS1 may be a potential therapeutic target for AML patients' treatment.

Background: Gastric cancer (GC) is one of the most common malignancies worldwide, exhibiting a high morbidity, and mortality. As the various treatment methods for gastric cancer are limited by disadvantages, many efforts to improve the efficacy of these treatments are being taken. Metabolic recombination is an important characteristic of cancer and has gradually caused a recent upsurge in research. However, systematic analysis of the interaction between glycolysis and GC patient prognosis and its potential associations with immune infiltration is lacking but urgently needed. Methods: We obtained the gene expression data and clinical materials of GC derived from The Cancer Genome Atlas (TCGA) dataset. Univariate and multivariate Cox proportional regression analyses were performed to select the optimal prognosis-related genes for subsequent modeling. We then validated our data in the GEO database and further verified the gene expression using the Oncomine database and PCR experiments. Besides, Gene set variation analysis (GSVA) analysis was employed to further explore the differences in activation status of biological pathways between the high and low risk groups. Furthermore, a nomogram was adopted to predict the individualized survival rate of GC patients. Finally, a violin plot and a TIMMER analysis were performed to analyse the characteristics of immune infiltration in the microenvironment. Results: A seven-gene signature, including STC1, CLDN9, EFNA3, ZBTB7A, NT5E, NUP50, and CXCR4, was established. Based on this seven-gene signature, the patients in the training set and testing sets could be divided into high-risk and low-risk groups. In addition, a nomogram based on risk and age showed good calibration and moderate discrimination. The results proved that the seven-gene signature had a strong capacity to predict the GC patient prognosis. Collectively, the violin plot and TIMMER analysis demonstrated that an immunosuppressive tumor microenvironment caused by hyperglycolysis led to poor prognosis. Conclusion: Taken together, these results established a genetic signature for gastric cancer based on glycolysis, which has reference significance for the in-depth study of the metabolic mechanism of gastric cancer and the exploration of new clinical treatment strategies.

Objective: To evaluate the safety and oncological outcomes of laparoscopic colorectal surgery using natural orifice specimen extraction (NOSE) compared with conventional laparoscopic (CL) colorectal surgery in patients with colorectal diseases. Methods: We conducted a systematic search of PubMed, EMBASE, and Cochrane databases for randomized controlled trials (RCTs), prospective non-randomized trials and retrospective trials up to September 1, 2018, and used 5-year disease-free survival (DFS), lymph node harvest, surgical site infection (SSI), anastomotic leakage, and intra-abdominal abscess as the main endpoints. Subgroup analyses were conducted according to the different study types [RCT and NRCT (non-randomized controlled trial)]. A sensitivity analysis was carried out to evaluate the reliability of the outcomes. RevMan5.3 software was used for statistical analysis. Results: Fourteen studies were included (two RCTs, seven retrospective trials and five prospective non-randomized trials) involving a total of 1,435 patients. Compared with CL surgery, the NOSE technique resulted in a shorter hospital stay, shorter time to first flatus, less post-operative pain, and fewer SSIs and total perioperative complications. Anastomotic leakage, blood loss, and intra-abdominal abscess did not differ between the two groups, while operation time was longer in the NOSE group. Oncological outcomes such as proximal margin [weighted mean difference [WMD] = 0.47; 95% confidence interval [CI] -0.49 to 1.42; P = 0.34], distal margin (WMD= -0.11; 95% CI -0.66 to 0.45; P = 0.70), lymph node harvest (WMD = -0.97; 95% CI -1.97 to 0.03; P = 0.06) and 5-year DFS (hazard ratio = 0.84; 95% CI 0.54-1.31; P = 0.45) were not different between the NOSE and CL surgery groups. Conclusions: Compared with CL surgery, NOSE may be a safe procedure, and can achieve similar oncological outcomes. Large multicenter RCTs are needed to provide high-level, evidence-based results in NOSE-treated patients and to determine the risk of local recurrence.

The natural product pectolinarigenin exerts anti-inflammatory activity and anti-tumor effects, and exhibits different biological functions, particularly in autophagy and cell cycle regulation. However, the antineoplastic effect of pectolinarigenin on glioblastoma (GBM) remains unclear. In the present study, we found that pectolinarigenin inhibits glioblastoma proliferation, increases autophagic flux, and induces cell cycle arrest by inhibiting ribonucleotide reductase subunit M2 (RRM2), which can be reversed by RRM2 overexpression plasmid. Additionally, pectolinarigenin promoted RRM2 protein degradation via autolysosome-dependent pathway by increasing autophagic flow. RRM2 knockdown promoted the degradation of CDK1 protein through autolysosome-dependent pathway by increasing autophagic flow, thereby inhibiting the proliferation of glioblastoma by inducing G2/M phase cell cycle arrest. Clinical data analysis revealed that RRM2 expression in glioma patients was inversely correlated with the overall survival. Collectively, pectolinarigenin promoted the degradation of CDK1 protein dependent on autolysosomal pathway through increasing autophagic flux by inhibiting RRM2, thereby inhibiting the proliferation of glioblastoma cells by inducing G2/M phase cell cycle arrest, and RRM2 may be a potential therapeutic target and a prognosis and predictive biomarker in GBM patients.

Liquid biopsy is attracting attention as a method of real-time monitoring of patients with tumors. It can be used to understand the temporal and spatial heterogeneity of tumors and has good clinical application prospects. We explored a new type of circulating tumor cell (CTC) enrichment technology combined with next-generation sequencing (NGS) to analyze the correlation between genomic alterations in circulating tumor cells of hepatocellular carcinoma and the counts of mesenchymal CTCs and CTC-associated white blood cell (CTC-WBC) clusters.

The mobilization of hematopoietic stem cells (HSCs) using granulocyte colony-stimulating factor is a classic method. Recently, a single injection of pegfilgrastim was used to mobilize CD34+ cells in some small-sample studies. To confirm the efficacy and safety of pegfilgrastim in the mobilization of CD34+ cells from healthy donors, we conducted a retrospective multicenter study. A total of 146 healthy donors who all received subcutaneous pegfilgrastim (12 mg) on day 1 were enrolled in our study. Donor HSC apheresis was conducted on day 5. The primary endpoint was the percentage of donors from whom ≥4 × 106 CD34+ cells/kg were collected in a single apheresis session. The median number of CD34+ cells in donors was significantly higher on day 5 than that on day 4 (82.26 μL vs. 51.65 μL, P ¡ 0.001). In 111 of the 146 donors, an optimal number of CD34+ cells (≥4 × 106 kg) were collected in a single apheresis procedure. Bone pain and headache were the main adverse events, but the side effects did not require treatment. The number of white blood cells in most donors dropped to normal levels within 1 week after apheresis. Nearly 97% of patients achieved neutrophil and platelet engraftment. Pegfilgrastim for mobilization could be used to obtain an optimal number of CD34+ cells in a single session. Pegfilgrastim-induced mobilization not only was effective and safe but also avoided the pain of multiple injections and apheresis procedures in donors. However, prospective randomized controlled trials should be conducted in the future.

We aimed to analyze the perioperative, functional, and oncologic outcomes following robot-assisted radical prostatectomy (RARP) and laparoscopic radical prostatectomy (LRP) for patients with localized prostate cancer (PCa) characterized by a large prostate volume (PV; ≥50 ml) over a minimum of 2 years follow-up.

To estimate the safety and efficiency of transvesical Retzius-sparing robot-assisted radical prostatectomy (T-RARP) compared with standard robot-assisted radical prostatectomy (S-RARP) for localized prostate cancer (PCa).

Background: This study aimed to develop an effective prognostic nomogram for predicting non-metastatic colon cancer. Methods: The Surveillance, Epidemiology, and End Results program was utilized to analyze patients who underwent surgical therapy (25,350 for training, 10,860 for validation). Nomograms were created depending upon multivariate analysis in the training cohort and were compared to current American Joint Committee on Cancer (AJCC) classifications. Areas under the receiver-operating characteristic curves (AUCs), Akaike's information criterions (AICs), and calibration curves were used. The clinical benefit was measured using decision curve analyses (DCAs). The validation cohort was used to validate the results. Results: Nomogram 1 included age, gender, histological grade, T stage, number of retrieved lymph nodes, tumor size, and N stage. Nomogram 2 included age, gender, histological grade, T stage, number of retrieved lymph nodes, tumor size, and number of positive lymph nodes. The prognostic discrimination of nomogram 1 (AUC, 0.729, 95% CI, 0.723-0.736) was better than that of nomogram 2 (AUC, 0.704, 95% CI, 0.698-0.710, p < 0.001) in five-year overall survival in the training cohort. Nomogram 1 (AIC, 137,319) also showed superior model-fitting compared to nomogram 2 (AIC, 137,453). Similarity, nomogram 1 was better than the AJCC 6th and 8th TNM classifications. DCA revealed that nomogram 1 had a superior net benefit than other models. These findings were validated using the validation cohort. Conclusions: The proposed nomogram 1 was a better prognostic prediction model with better discrimination and superior model-fitting for patients with non-metastatic colon cancer, which might prove to be clinically helpful.

Background: The outlook for patients with esophageal and gastric (EG) cancer remains poor. Hence, there is a compelling need to identify novel treatment strategies and complementary biomarkers. Programmed death ligand 1 (PD-L1) and mismatch repair deficiency (dMMR) are putative biomarkers of response to immune-checkpoint blockade, but their prognostic value and interrelationship in EG cancer have been sparsely investigated. Methods: Immunohistochemical expression of PD-L1 on tumour cells (TC) and tumour-infiltrating immune cells (TIC), and of PD-1 (programmed death receptor 1) on TIC was assessed using tissue microarrays with primary tumours and a subset of paired lymph node metastases from a consecutive, retrospective cohort of 174 patients with chemoradiotherapy-naïve EG adenocarcinoma. MMR proteins MLH1, PMS2, MSH2, and MSH6 were assessed by immunohistochemistry. The total number (intratumoural, tumour-adjacent, and stromal) of CD8+ T cells in each core was calculated by automated analysis. Results: High PD-L1 expression on both TC and TIC, but not PD-1 expression, was significantly associated with dMMR. PD-L1 expression on TIC was significantly higher in lymph node metastases than in primary tumours. High expression of PD-L1 or PD-1 on TIC was significantly associated with a prolonged survival, the former independently of established prognostic factors. A significant stepwise positive association was found between CD8+ T cells and categories of PD-L1 expression on TIC. Conclusion: PD-L1 expression on TIC is higher in lymph node metastases compared to primary tumours, correlates with dMMR, and is an independent factor of prolonged survival in patients with chemoradiotherapy-naïve EG adenocarcinoma. These findings suggest that PD-L1 expression on TIC may be a useful biomarker for identifying patients who may not need additional chemo- or chemoradiotherapy, and who may benefit from PD-1/PD-L1 immune-checkpoint blockade.

Accurate assessment of predictive biomarker expression is critical in patient selection in clinical trials or clinical practice. However, changes in biomarker expression may occur after treatment. The aim of the present study was to evaluate the effects of chemotherapy on MET expression in gastric cancer (GC).

To assess the perioperative, functional, and oncological outcomes of transvesical robot-assisted radical prostatectomy (T-RARP) and posterior robot-assisted radical prostatectomy (P-RARP) for localized prostate cancer.

Esophageal cancer is a type of gastrointestinal carcinoma and is among the 10 most common causes of cancer death worldwide. However, the specific mechanism and the biomarkers in the proliferation and metastasis of esophageal tumors are still unclear. Therefore, the development of several natural products which could inhibit esophageal tumors deserve attention. In the present study, different sources of cancer cells were used to select the sensitive cell line (esophageal cancer cell KYSE450) and the proper dose of angustoline, which were utilized in the following cell viability, migration and invasion assays. Then the lipidomic detection of clinical samples (tissue and blood plasma) from esophageal cancer patients was performed, to screen out the specific phospholipid metabolites [PC (16:0/18:1) and LPC (16:0)]. Considering lysophosphatidylcholine acyltransferase 2 (LPCAT2) was tightly relative with phospholipids conversion, serine/threonine-protein kinase 11 (LKB1), 5'-monophosphate (AMP)-activated protein kinase (AMPK) and embryonic lethal, and abnormal vision, drosophila-like 1 (ELAVL1) were investigated, to evaluate their expression levels in esophageal tumor tissue and KYSE450 cells. Additionally, KYSE450 tumor bearing mouse model was constructed, the role of angustoline in inhibiting esophageal tumors through regulating LKB1/AMPK/ELAVL1/LPCAT2 pathway was validated, and found that the conversion from LPC (16:0) to PC (16:0/18:1) was blocked by angustoline in some degree. The above results for the first time proved that angustoline suppressed esophageal tumors through activating LKB1/AMPK and inhibiting ELAVL1/LPCAT2, which consequently blocked phospholipid remodeling from LPC (16:0) to PC (16:0/18:1).