Overexpression of Long Non-Coding RNA TUG1 Promotes Colon Cancer Progression.

BACKGROUND Colon cancer is one of the most prevalent and deadly cancers worldwide. It is still necessary to further define the mechanisms and explore therapeutic targets of colon cancer. Dysregulation of long noncoding RNAs (lncRNAs) has been shown to be correlated with diverse biological processes, including tumorigenesis. This study aimed to characterize the biological mechanism of taurine-upregulated gene 1 (TUG1) in colon cancer. MATERIAL AND METHODS qRT-PCR was used to analyze the expression level of TUG1 and p63 in 75 colon cancer tissues and the matched adjacent non-tumor tissue. In vitro, cultured colon cancer cell lines HCT-116 and LoVo were used as cell models. TUG1 and p63 were silenced via transferring siRNA into HCT-116 or LoVo. The effects of TUG1 were investigated by examining cell proliferation, apoptosis, and migration. RESULTS Among the 75 colon cancer cases, the expression of TUG1 was significantly higher in colon cancer tissues compared with the matched adjacent non-tumor tissue, while p63 expression was lower in the tumor tissue. In HCT-116 and LoVo, the expression of TUG1 was significantly increased by p63 siRNA transfection. Furthermore, down-regulation of TUG1 by siRNA significantly inhibited the cell proliferation and promoted colon cancer cell apoptosis. In addition, inhibition of TUG1 expression significantly blocked the cell migration ability of colon cancer cells. CONCLUSIONS LncRNA TUG1 may serve as a potential oncogene for colon cancer. Overexpressed TUG1 may contribute to promoting cell proliferation and migration in colon cancer cells.

Comparison of lymph node number and prognosis in gastric cancer patients with perigastric lymph nodes retrieved by surgeons and pathologists.

OBJECTIVE: To compare the numbers of positive and total lymph nodes and prognosis in gastric cancer patients whose perigastric lymph node retrieval was performed by surgeons and pathologists. METHODS: We conducted a retrospective analysis of clinical and follow-up data from 1, 056 patients who underwent gastric cancer D2 radical lymph node resection between January 2008 and December 2010 in the Gastrointestinal Surgery Department of Yantai Yuhuangding Hospital. The follow-up ended in December 2015. Patients were divided into two groups according to the specialty of physicians who performed the postoperative perigastric lymph node retrieval: the surgeon group (475 cases) and the pathologist group (581 cases). The numbers of positive and total perigastric lymph nodes and the 3- and 5-year survival were compared between gastric cancer patients in the two groups overall and stratified by TNM stage (the 7th Edition of the American Joint Committee on Cancer). RESULTS: Overall, the numbers of positive and total lymph nodes were significantly higher in the surgeon group than in the pathologist group (6.53±4.07 vs. 4.09±3.70, P=0.021; 29.64±11.50 vs. 20.71±8.56, P<0.001). Further analysis showed that the total number of lymph nodes in stage I patients (19.40±9.62 vs. 15.45±8.59, P=0.011) and the numbers of positive and total lymph nodes in stage II (1.38±1.08 vs. 0.87±1.55, P=0.031; 25.35±10.80 vs. 16.75±8.56, P<0.001) and stage III patients (8.11±6.91 vs. 6.66±5.12, P=0.026; 32.34±12.55 vs. 25.45±8.31, P<0.001) were significantly higher in the surgeon group than in the pathologist group. The survival analysis showed that the 3- and 5-year survival of stage II and III patients was significantly higher in the surgeon group than in the pathologist group (82.0% vs. 73.1%, 69.5% vs. 61.2%, P=0.038; 49.2% vs. 38.9%, 36.3% vs. 28.0%; P=0.045). CONCLUSIONS: Compared with retrieval performed by pathologists, postoperative perigastric lymph node retrieval performed by surgeons was associated with significant increase in the total lymph node number of stage I patients, the numbers of positive and total lymph nodes of stage II and III patients, and the survival of stage II and stage III gastric cancer patients.

Deciphering the multidimensional impact of IGFBP1 expression on cancer prognosis, genetic alterations, and cellular functionality: A comprehensive Pan-cancer analysis.

Objectives: IGF-binding protein 1 (IGFBP1) is a key regulator of insulin-like growth factors, impacting biological processes, including cancer progression and prognosis. Materials and methods: This study investigates genetic alterations affecting IGFBP1 expression in tumors using data from The Cancer Genome Atlas (TCGA) PanCancer Atlas via cBioPortal. We analyzed samples from 32 cancer types for mutation sites, including deep deletions, amplifications, and mutations. RNA-seq data were normalized using log2(value + 1). Statistical analyses, including survival outcomes, were conducted using R packages like ggplot2, stats, and car. Kaplan-Meier survival curves and log-rank tests assessed overall survival (OS) and progression-free survival (PFS). Univariate Cox regression was used to develop nomogram models for OS. Functional consequences of IGFBP1 mutations were explored through protein structure, stability, and IGF interaction analyses. Protein-protein interaction networks and functional enrichment were analyzed using GEPIA2, STRING, and Cytoscape. Gene Ontology (GO), KEGG, and Gene Set Enrichment Analysis (GSEA) provided insights into affected biological pathways. Results: Pan-cancer analysis revealed diverse expression patterns, including significant upregulation in cutaneous melanoma (SKCM) and downregulation in lung adenocarcinoma (LUAD) and stomach adenocarcinoma (STAD). Specifically, elevated IGFBP1 expression in SKCM patients led to a 25 % improvement in 5-year survival. In contrast, higher IGFBP1 levels in LUAD and OV patients resulted in a 30 % and 20 % decrease in survival, respectively. Elevated IGFBP1 levels are significantly linked to advanced tumor stage and grade in OV and LUAD, affecting prognostic outcomes. Nomogram models for OV, SKCM, LUAD, and STAD showed IGFBP1's predictive strength with AUC values ranging from 0.70 to 0.85, indicating its diagnostic potential. Genetic analyses revealed mutations in IGFBP1 in 12 % of STAD cases and 10 % of UCEC cases, indicating significant genetic variation. Immune analysis showed that high IGFBP1 expression significantly influenced immune cell infiltration, particularly macrophages and CD8+ T cells, thereby affecting survival in LUAD and OV. Functional enrichment and gene set enrichment analysis identified IGFBP1 involvement in crucial pathways, such as cell cycle regulation, immune response, and PD-1 signaling, highlighting its biological impact. Additionally, IGFBP1 expression delineates distinct molecular and immune subtypes, correlating with specific cancer behaviors and immune patterns. Conclusions: These findings highlight IGFBP1's potential as a biomarker and therapeutic target, particularly for immunoregulation and cancer subtype stratification.

IGFL2 expression and surgical volume: Independent predictors of survival in gastric cancer.

This study aimed to assess the impact of surgeons' annual volume and insulin-like growth factor-like family member 2 (IGFL2) expression on gastric cancer prognosis. Clinicopathological data from 475 patients who underwent D2 lymph node dissection were analyzed. IGFL2 expression was evaluated using immunohistochemistry. Patients were divided into training (70%) and validation (30%) groups. Univariate and multivariate Cox regression identified risk factors for overall survival (OS) and disease-free survival (DFS), leading to a clinical prediction model. Model performance was evaluated using C-index. High IGFL2 expression and low surgical volume independently predicted poorer OS and DFS (hazard ratio = 2.13, 2.17, all P < .01). Surgeons performing >26 cases annually had higher OS and DFS (hazard ratio = 1.65, 1.58, all P < .01). Nomograms integrating surgical volume, IGFL2 expression, grade, TNM staging, and carcinoembryonic antigen showed superior predictive accuracy for OS and DFS compared to TNM alone, with robust C-indices and area under the curve values. Surgeons' annual volume and IGFL2 expression independently predict gastric cancer prognosis, emphasizing the need for specialized training and further research on IGFL2's molecular mechanisms to enhance patient outcomes.

The meta-analysis of sister chromatid exchange as a biomarker in healthcare workers with occupational exposure to antineoplastic drugs.

BACKGROUND: Sister chromatid exchange (SCE) can be used to identify early occupational health status in health care workers. Our aim is to comprehensively assess the relationship between long-term exposure to antineoplastic drugs (ADs) and SCE in health care workers via meta-analysis. METHODS: Five databases were systematically searched for relevant articles published from inception to November 30, 2022. Literature data are expressed as mean difference and 95% confidence intervals (CI) or relative risk and 95% CI. For I2 > 50% trials, random effect model is used for statistical analysis, otherwise fixed effect model is used. This review was registered in the International Prospective Register of Systematic Reviews (identifier CRD42023399914). RESULTS: Fourteen studies were included in this study. Results showed the level of SCE in healthcare workers exposed to ADs was significantly higher than in controls. The mean difference of the SCE trial was 0.53 (95% CI: 0.10-0.95, P = .01) under a random-effects model. CONCLUSIONS: The findings suggested a significant correlation between occupational exposure to ADs in health care workers and SCE, requiring the attention of health care workers in general.

Biofouling mitigation and microbial community dynamics in the membrane bioreactor by the indigenous quorum quenching bacterium Delftia sp. JL5.

The quorum quenching (QQ) strategy has attracted increasing attention in membrane bioreactor (MBR) fouling control. However, the applicable QQ strain remains limited. This study investigated the antibiofouling performance of a new indigenous QQ bacterium, Delftia sp. JL5 (JL5) in MBR. JL5 produces intracellular acylase that irreversibly degrades N-acylhomoserine lactones (AHL), inhibited biofilm formation of quorum-sensing bacteria from activated sludge. During 120 days of operation, immobilized JL5 substantially delayed MBR biofouling by 2.1 and 2.9 times, at a flux rate of 30 L/(m2·h) and 20 L/(m2·h), respectively. A slower flux rate was favorable for effective mitigation of JL5 biofouling. JL5 reduced the AHL and extracellular polymeric substances of biocake without affecting the efficiency of waste removal. The presence of JL5 significantly changed the microbial structure of the membrane biocake, but not the activated sludge. Collectively, high activity, durability, and acid tolerance credited JL5 as a promising strain for QQ-MBR.

Efficacy of the Short-Term versus Long-Term Administration of Antimicrobial Prophylaxis in Gastric Cancer Surgery: A Meta-Analysis of Randomized Controlled Trials.

Background: We performed a meta-analysis to confirm the efficacy of short-term compared with long-term administration of antimicrobial prophylaxis in gastric cancer surgery. Methods: Randomized controlled trials of the efficacy of short-term versus long-term administration of antimicrobial prophylaxis in gastric cancer surgery were searched using the MEDLINE, EMBASE, and the Cochrane Controlled Trials Register databases. The data were evaluated and statistically analyzed using RevMan version 5.3.0. Five studies including 2,053 participants who received short-term versus long-term administration of antimicrobial prophylaxis in gastric cancer surgery were considered. Results: There was no significant difference in the surgical site infection (SSI) rate between the short-term group and the long-term group (8.1% vs. 9.2%; odds ratio [OR], 0.87; 95% confidence interval [CI], 0.64-1.09; p = 0.39). Hierarchical analysis also showed no significant differences in incisional-site incisions, organ/space incisions, or leakage. Multivariable analysis showed no significant differences in gender, age (>65 years), body mass index (>25 kg/m2), D2, operation time (>3 hours), pathologic stage 3, blood loss, combined resection, diabetes mellitus, total gastrectomy, or blood transfusion between the two groups. Conclusions: Short-term administration of antimicrobial prophylaxis did not increase the incidence of SSIs after gastrectomy.

Risk factor analysis and construction of prediction models for short-term postoperative complications in patients undergoing gastrointestinal tract surgery.

Purpose: To identify risk factors associated with short-term postoperative complications in patients with gastrointestinal cancer and develop and validate prediction models to predict the probability of complications. Methods: A total of 335 patients enrolled in the primary cohort of this study were divided into training and validation sets in a chronological order. Using univariate and multivariate logistic regression analyses, the risk factors for postoperative complications were determined, and nomogram prediction models were constructed. The performance of the nomogram was assessed with respect to the receiver operator characteristic and calibration curves. Results: Patients with complications had a stronger postoperative stress response and a longer duration of daily fluid intake/output ratio >1 after surgery. Logistic analysis revealed that body mass index (BMI), body temperature on POD4 (T.POD4), neutrophil percentage on POD4 (N.POD4), fasting blood glucose on POD4 (FBG.POD4), and the presence of fluid intake/output ratio <1 within POD4 were risk factors for POD7 complications, and that BMI, T.POD7, N.POD7, FBG.POD4, FBG.POD7, and the duration of daily fluid intake/output ratio >1 were risk factors for POD30 complications. The areas under the curve of Nomogram-A for POD7 complications were 0.867 and 0.833 and those of Nomogram-B for POD30 complications were 0.920 and 0.918 in the primary and validation cohorts, respectively. The calibration curves showed good consistency in both cohorts. Conclusion: This study presented two nomogram models to predict short-term postoperative complications in patients with gastrointestinal cancer. The results could help clinicians identify patients at high risk of complications within POD7 or POD30.

Sclerosing pneumocytoma mixed with a columnar clear cell adenoma and a typical carcinoid: case report and review of literature.

Sclerosing pneumocytoma (SP) is a rare and benign tumor predominantly occurring in Asian women, easily misdiagnosed by imaging and pathologic frozen diagnosis during surgery because of its diverse histomorphology (4 structures, 2 types of cells). It may form multiple tumors. When SP is combined with carcinoid, adenoma, or other tumors (although rare), diagnosis is more complicated. SP mixed with carcinoid tumor is rare. At present, only 4 cases have been reported in English literature. Here, we report a case of sclerosing pneumocytoma combined not only with carcinoid, but also with clear cell adenoma of the lung. The patient was a 52-year-old female and CT found a nodule in the middle lobe of the right lung. SP was not excluded by intraoperative frozen section diagnosis. The above 3 components formed a 1.4 cm nodule. The related literature is reviewed to strengthen the understanding of SP, and aid clinicopathological diagnosis.

Effect of Th9/IL-9 on the growth of gastric cancer in nude mice.

OBJECTIVE: By neutralizing IL-9 in a nude mouse model, the study aimed to investigate the role of Th9/IL-9 on the growth of gastric cancer in mice. MATERIALS AND METHODS: Male BALB/c nude mice were randomly divided into three groups: a normal control group (Control), an SGC-7901 xenografted nude mice model group (Model), and a rIL-9 treatment group (Treat). The weight of the tumors was recorded to calculate the tumor inhibition rate. Flow cytometry was used to detect the cell frequency of Th9, Th17, and Treg in peripheral blood. The IL-4, IL-9, IL-10, IL-25, VEGF, and TGF-ß levels in serum were determined by ELISA. The cellular migration and invasion were investigated by transwell assay. Immunohistochemical and Western blot were used to detect the expression of IL-9, CD34, PU.1, p53, and p21 proteins in gastric cancer tissue. The mRNA expression levels of IL-9, IL-21, and PU.1 in gastric cancer tissue were determined by qRT-PCR. RESULT: rIL-9 can significantly inhibit the growth of gastric cancer. The frequency of Th9, Th17, and Treg in peripheral blood was decreased upon treatment. The levels of IL-4, IL-9, IL-10, IL-25, VEGF, and TGF-ß in serum were significantly reduced in the Treat group compared with the Model group (P<0.05). rIL-9 can inhibit cellular migration and invasion and reduce the mRNA level of IL-9, IL-21, and PU.1. Meanwhile, in the Treat group, the expression of IL-9, CD34, and PU.1 was significantly reduced, whereas the expression of p53 and p21 was significantly increased compared with the Model group (P<0.05). CONCLUSION: This study suggested that Th9/IL-9 has a deleterious role in gastric cancer.

Expression and clinical significance of H-caldesmon in gastrointestinal stromal tumor: is it a specific marker for myogenic differentiation?

OBJECTS: To investigate the expression and clinical significance of H-caldesmon which is considered a myogenic marker in GIST. METHODS: The clinical information of 105 patients diagnosed with GIST was obtained from Yantai Yuhuangding Hospital and Rambam Health Care Campus. Morphology, the results of immunohistochemical staining and available molecular detection were reviewed. The expression of H-caldesmon was detected for each specimen by immunohistochemical staining. Comparative analysis was carried out between H-caldesmon expression and clinicopathologic parameters. RESULTS: H-caldesmon was expressed in all patients with GIST including tumors outside the gastrointestinal tract and with CD117-negative expression. Although the pattern of expression was different, the positive rate in our study group was 100%. There was no statistically difference between H-caldesmon expression and parameters such as gender, age, location, morphology, risk, immunologic markers, and molecular mutation. CONCLUSIONS: H-caldesmon is expressed positively in GIST and might not be a specific marker for smooth muscle and associated tumors. GIST outside the gastrointestinal tract or with CD117-negative expression should not be misdiagnosed assmooth muscle tumor because of the positive expression of H-caldesmon in the differential diagnosis. Comprehensive analysis combined with other immunological markers and molecular detection is needed.

Effect of long non-coding RNA AOC4P on gastrointestinal stromal tumor cells.

OBJECTIVE: In this research, we explored the effect of long non-coding RNA (lncRNA) AOC4P on gastrointestinal stromal tumor (GIST) cells. MATERIALS AND METHODS: The expression of lncRNA AOC4P in tissues was detected by real-time PCR (RT-PCR). The epithelial-mesenchymal transition (EMT)-related proteins in tissues were analyzed by Western blot. The experiment included negative control group (CN), silence AOC4P group (si AOC4P), and silence negative control group (si CT). RT-PCR, MTT, Scratch, Transwell, and Annexin V-FITC methods were used to detect the expression of lncRNA AOC4P, cell proliferation, cell migration ability, cell invasion ability, and apoptosis, respectively. The EMT-related proteins including TGF-ß, ZEB1, Vimentin, Snail, and E-cadherin were analyzed by Western blot. RESULTS: The expression of lncRNA AOC4P and the expression of EMT-related proteins in high-risk GISTs were higher than that in low- and intermediate-risk GISTs (P<0.05). It was revealed that cell proliferative migration and invasive ability in si AOC4P group was decreased than that in CN and si CT groups (P<0.05), and cell apoptosis in si AOC4P group was higher than that in si CT group. The results of Western blot demonstrated that the expression of TGF-ß1, ZEB1, Vimentin, and Snail in si AOC4P group were lower than that in si CT and CN group (P<0.05), and the expression of E-cadherin in si AOC4P group was higher than that in si CT and CN group (P<0.05).

Expression of BMP-4 in papillary thyroid carcinoma and its correlation with tumor invasion and progression.

Bone morphogenetic protein 4 (BMP-4) is a member of the BMP protein family. BMP-4 was reported to induce epithelial-mesenchymal transition (EMT) and promote tumor cell immigration and invasion. This study aimed to investigate the expression of BMP-4 in papillary thyroid carcinoma (PTC) and its correlation with the patients' clinicophathological features and with tumor invasion and metastasis. Surgically resected PTC specimens from 82 patients admitted to the Department of Thyroid Surgery of Yantai Yuhuangding Hospital between Feb 1st and May 31st, 2016 were collected. The expression level of BMP-4 in PTC tissues was examined by immunohistochemical staining. The full clinical records of all patients were collected to analyze the relevance between BMP-4 expression and the clinical pathological features of PTC. Our result showed that BMP-4-positive cell rate and staining intensity were positively correlated with the patient's age (P=0.031, 0.037), tumor size (P=0.033, 0.019), capsular invasion (P=0.001, 0.002) and TNM stage (P=0.001, 0.004), while not correlated with gender, multicentricity of tumor or lymphatic metastasis. In conclusion, this study identified BMP-4 as a potential molecular marker for predicting the invasion and progression of PTC.

Expression of PIN1 in Gastrointestinal Stromal Tumours and its Clinical Significance.

BACKGROUND: The malignancy of gastrointestinal stromal tumours (GIST) varies greatly. Due to the uncertainty of specific molecular pathogenesis and complexity of biological behaviour of GIST, the aggressiveness and prognosis of GIST cannot be precisely predicted. MATERIALS AND METHODS: We retrieved 40 paraffin-embedded specimens of surgically resected GIST between January 2013 and May 2015 at the Pathology Department of Yuhuangding Hospital Affiliated to Qingdao University and detected the expression of NIMA-interacting peptidylprolyl isomerase (PIN1) and Ki67, by immunohistochemical methods. RESULTS: The positivity rate of PIN1 and Ki67 in GIST was 80% and 32.5%, respectively. The expression of PIN1 was associated with risk of malignancy, tumour location, tumour size, and mitotic counts. The expression of Ki67 was also associated with risk of malignancy, tumour location, tumour size, and mitotic counts. The expression of Ki67 was positively related to the expression of PIN1. CONCLUSION: PIN1 and Ki67 may be potential factors predicting the malignancy of GIST. PIN1 may be an attractive prognostic indicator and therapeutic target for GIST.

Silencing of LncRNA HULC Enhances Chemotherapy Induced Apoptosis in Human Gastric Cancer.

BACKGROUND: Gastric cancer (GC) is one of the most common cancers in the world; however, chemoresistance greatly decreases the efficacy of therapy in gastric cancer. Long noncoding RNAs (IncRNAs) participate in a variety of biological processes, and we hypothesize that lncRNA HULC regulates the multidrug resistance in GC treatment. METHODS: We obtained GC tissue samples from 42 GC patients and detected the expression level of HULC in the plasma and tissues via qRT-PCR. The relationship between HULC expression and survival rate was confirmed by Kaplan-Meier survival analysis. We verified the expression of HULC in GC cell lines via qRT-PCR, and the function of HULC was detected via flow cytometry assay and CCK-8 assay. RESULTS: HULC was highly expressed in the plasma and tissues of the GC patients compared with controls, with HULC high expression indicating lower survival rate. HULC knockdown enhanced cisplatin-induced apoptosis in GC cells. CONCLUSIONS: Our results suggest that silencing lncRNA HULC could enhance chemotherapy induced apoptosis in GC cells, which could provide a novel approach for therapeutic strategies.

BRAF-Activated Long Noncoding RNA Modulates Papillary Thyroid Carcinoma Cell Proliferation through Regulating Thyroid Stimulating Hormone Receptor.

PURPOSE: The importance of long noncoding RNAs (lncRNAs) in tumorigenesis has recently been demonstrated. However, the role of lncRNAs in development of thyroid cancer remains largely unknown. MATERIALS AND METHODS: Using quantitative reverse transcription polymerase chain reaction, expression of three lncRNAs, including BRAF-activated long noncoding RNA (BANCR), papillary thyroid cancer susceptibility candidate 3 (PTCSC3), and noncoding RNA associated with mitogen-activated protein kinase pathway and growth arrest (NAMA), was investigated in the current study. RESULTS: Of the three lncRNAs (BANCR, PTCSC3, and NAMA), expression of BANCR was significantly up-regulated while PTCSC3 and NAMA were significantly down-regulated in papillary thyroid carcinoma (PTC) compared to that in normal tissue. BANCR-knockdown in a PTC-derived cell line (IHH-4) resulted in significant suppression of thyroid stimulating hormone receptor (TSHR). BANCR-knockdown also led to inhibition of cell growth and cell cycle arrest at G0/G1 phase through down-regulation of cyclin D1. In addition, BANCR was enriched by polycomb enhancer of zeste homolog 2 (EZH2), and silencing BANCR led to decreased chromatin recruitment of EZH2, which resulted significantly reduced expression of TSHR. CONCLUSION: These findings indicate that BANCR may contribute to the tumorigenesis of PTC through regulation of cyclin D1 and TSHR.

Application experience of intraoperative neuromonitoring in thyroidectomy.

OBJECTIVE: The aim of this study is to summarize the experience of intraoperative neuromonitoring system for monitoring and protection of recurrent laryngeal nerve during thyroid surgery. METHODS: There were 220 cases in this study, male 53, female 167, mean age 38.2 years old. 85 cases in the study had thyroid cancer, 19 cases had thyroid benign tumor, 90 cases had thyroid goiter, 3 cases had Hashimoto's diseases, and 23 cases had hyperthyroidism. The tumor diameters were over than 5 cm in 113 cases. In the procedure, two recording needle electrodes were put into cricothyroid muscle; one stimulator electrodes was explored in tracheo-asophageal groove, if recurrent laryngeal nerves were right there or near, doctors could see the electromyogram and hear the toot honk. With careful dissection, recurrent laryngeal nerve could be found out till explored into the larynx site. RESULTS: 207 cases (278 sizes) of 220 were finished, electromyogram was not drawn out in 13 cases; 9 cases were false-negative because of system and anesthesia questions; needle electrodes cannot be put in properly in 4 cases because of cricothyroid muscle cancer invasion. No permanent recurrent laryngeal nerve paralysis occurred, 2 cases with transient nerve paralysis recovered in one month. CONCLUSION: The intraoperative neuromonitoring system can avoid damage of the recurrent laryngeal nerves when exposing the recurrent laryngeal nerve in the whole operation, therefore, with less medical complications.