A positive feedback between PDIA3P1 and OCT4 promotes the cancer stem cell properties of esophageal squamous cell carcinoma.

BACKGROUND: Increasing evidence has indicated that long non-coding RNAs (lncRNAs) have been proven to regulate esophageal cancer progression. The lncRNA protein disulfide isomerase family A member 3 pseudogene 1 (PDIA3P1) has been shown to promote cancer stem cell properties; however, its mechanism of action remains unclear. In this study, we investigated the regulation of esophageal cancer stem cell properties by the interaction of PDIA3P1 with proteins. METHODS: The GEPIA2 and Gene Expression Omnibus databases were used to analyze gene expression. PDIA3P1 expression in human esophageal squamous cell carcinoma (ESCC) tissues and cell lines was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Loss-of-function experiments were performed to determine the effects of PDIA3P1 on ESCC cell proliferation, migration, and invasion. The sphere formation assay, number of side population cells, and CD271 + /CD44 + cells were detected by flow cytometry to identify the cancer stem cell properties. RNA immunoprecipitation (RIP), RNA pull-down, co-immunoprecipitation (co-IP), dual luciferase reporter, and cleavage under targets and tagmentation (CUT&Tag) assays were performed to elucidate the underlying molecular mechanisms. RESULTS: PDIA3P1 expression was upregulated in ESCC cell lines and tissues. Functionally, higher PDIA3P1 expression promoted cell proliferation, invasion, and metastasis and inhibited apoptosis in esophageal cancer. Importantly, PDIA3P1 promoted cancer stem cell properties in ESCC. Mechanistically, PDIA3P1 interacted with and stabilized octamer-binding transcription factor 4 (OCT4) by eliminating its ubiquitination by the ubiquitinating enzyme WW domain-containing protein 2 (WWP2). Moreover, as a transcription factor, OCT4 bound to the PDIA3P1 promoter and promoted its transcription. CONCLUSIONS: Our research revealed a novel mechanism by which a positive feedback loop exists between PDIA3P1 and OCT4. It also demonstrated that the PDIA3P1-WWP2-OCT4 loop is beneficial for promoting the cancer stem cell properties of ESCC. Owing to this regulatory relationship, the PDIA3P1-WWP2-OCT4-positive feedback loop might be used in the diagnosis and prognosis, as well as in the development of novel therapeutics for esophageal cancer.

Identification and validation of a novel NK cells-related signature to predict prognosis and immune microenvironment in LUAD.

BACKGROUND: The prevalence and fatality rates of lung cancer are experiencing a rapid escalation. Natural Killer (NK) cells have been established to have a crucial role in both tumor initiation and progression. Nevertheless, uncertainties persist regarding their precise implications in the prognosis of LUAD. METHODS: The data were obtained from reputable sources, such as the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) database, and our internally generated sequencing data. Utilizing the TCGA data as a background, we selected intersecting genes, validated by cluster analysis, to establish a Cox model and validated it using the GEO datasets. Furthermore, we conducted extensive analyses to investigate the significance of potential biomarkers in relation to immune cell infiltration, single-cell data, differential gene expression, and drug sensitivity. RESULTS: 67 immune-related genes associated with NK cells (NK-IRGs) were identified in the TCGA datasets, whose research potential was demonstrated by cluster analysis. A prognostic signature was identified utilizing the univariate and multivariate Cox model, resulting in the identification of five genes, which was validated using GEO datasets. Additionally, the nomogram's calibration curve demonstrated exceptional concordance between the projected and actual survival rates. Subsequent investigations uncovered that this prognostic signature demonstrated its independence as a risk factor. Notably, in the low-risk group, NK cells exhibited elevated levels of immune checkpoint molecules, indicating heightened sensitivity to immune therapy. These findings highlight the potential of utilizing this signature as a valuable tool in the selection of patients who could benefit from targeted immune interventions.

Improvement in the performance of an autoantibody panel in combination with heat shock protein 90a for the detection of early­stage lung cancer.

The early diagnosis of lung cancer is closely associated with the decline of mortality. A panel consisting of seven lung cancer-related autoantibodies (7-AABs) has been shown to be a reliable and specific indicator for the early detection of lung cancer, with a specificity of ~90% and a positive predictive value of ~85%. However, its low sensitivity and negative predictive value limit its wide application. To improve its diagnostic value, the diagnostic efficiencies of 7-AABs in combination with non-specific tumor markers were retrospectively investigated for the detection of early-stage lung cancer. A total of 217 patients with small lung nodules who presented with ground-glass opacity or solid nodules as well as 30 healthy controls were studied. The concentrations of 7-AABs and heat shock protein 90a (HSP90a) were assessed using ELISA. Automated flow fluorescence immune analysis was used for the assessment of CEA, CYFRA21-1, CA199 and CA125 levels. The results showed that 7-AABs + HSP90a possessed a remarkably improved diagnostic efficiency for patients with small pulmonary nodules or for patients with lung nodules of different types, which suggested that 7-AABs in combination with HSP90a could have a high clinical value for the improvement of the diagnostic efficiency of early-stage lung cancer.

The roles and mechanisms of the lncRNA-miRNA axis in the progression of esophageal cancer: a narrative review.

Background and Objective: Esophageal cancer is one of the most common malignant digestive tract tumors. Despite various treatment methods, the prognosis of patients remains unsatisfactory, largely due to an insufficient understanding of the mechanisms involved in the pathogenesis and progression of esophageal cancer. More than 98% of the nucleotide sequences in the human genome do not encode proteins, and their transcription products are noncoding RNAs (ncRNAs), mainly long noncoding RNAs (lncRNAs) and microRNAs (miRNAs). Experiments have shown that lncRNAs and miRNAs play crucial roles in the occurrence and progression of various human malignancies. These ncRNAs influence the progression of esophageal cancer through an intricate regulatory network. We herein summarized the roles and mechanisms of the lncRNA-miRNA axis in esophageal cancer cell proliferation, apoptosis, epithelial-mesenchymal transition (EMT), invasion and metastasis, drug resistance, radiotherapy resistance, and angiogenesis. This review provides a rationale for anticancer therapy that targets the lncRNA-miRNA axis in esophageal cancer. Methods: Related articles published in the PubMed database between 05/30/2008 to 09/10/2022 were identified using the following terms: "lncRNA AND miRNA AND esophageal cancer", "lncRNA AND miRNA AND cell proliferation", "lncRNA AND miRNA AND apoptosis", "lncRNA AND miRNA AND EMT", "lncRNA AND miRNA AND invasion and metastasis", "lncRNA AND miRNA AND drug resistance", and "lncRNA AND miRNA AND radiotherapy resistance". Published articles written in English available to readers were considered. Key Content and Findings: We summarized the roles of the lncRNA-miRNA axis in the progression of esophageal cancer, including cell proliferation, apoptosis, EMT, invasion and metastasis, drug resistance, radio resistance, and other progressions, and determined that the lncRNA-miRNA axis may serve as a potential clinical treatment target for esophageal cancer. Conclusions: The lncRNA-miRNA axis is closely related to the progression of esophageal cancer and may act as a potential biological target for the clinical treatment of patients with esophageal cancer.

miR-375 suppresses the growth and metastasis of esophageal squamous cell carcinoma by targeting PRDX1.

Background: Esophageal cancer (EC) is one of the most lethal cancers. Esophageal squamous cell carcinoma (ESCC) is the most common histological subtype in Asian people. Diverse microRNAs, such as miR-375, have been confirmed to be involved in the process of tumorigenesis and metastasis. However, the underlying mechanism through which miR-375 acts in ESCC patients remains unknown. Methods: We used The Cancer Genome Atlas (TCGA) database to analyze the association between miR-375 and the survival rate in patients with esophageal squamous cell carcinoma. Real Time quantitative PCR (RT-qPCR) analysis was performed to evaluate the level of miR-375 in EC tissues and cells. A luciferase reporter assay was used to confirm the target gene of miR-375. A colony formation assay as well as flow cytometric and transwell invasion experiments were employed to examine the effects of miR-375 and peroxiredoxin 1 (PRDX1) on ESCC cells. A tumor xenograft mouse model was then used to investigate the role of miR-375 on tumor growth in vivo. Moreover, we performed rescue experiments to evaluate the effect of PRDX1 on ESCC progression. Results: miR-375 expression was significantly downregulated in both ESCC clinical tissues and serum, and the reduction of miR-375 was remarkably linked to a poor prognosis in ESCC. Further investigation illustrated that aberrant expression of miR-375 dampened the growth and infiltration of ESCC cells both in vitro and in vivo. Bioinformatics and luciferase reporter analysis verified that the transcript of PRDX1 is a direct target of miR-375 and its expression in ESCC cells was found to be inversely modulated by miR-375. Moreover, the tumor formation experiment in nude mice confirmed that miR-375 can effectively dampen tumor growth in xenograft tumor mice models. Notably, over-expression of PRDX1 effectively counteracted the tumor-suppressing capabilities of miR-375. Conclusions: We demonstrated the antitumor effect of miR-375 on ESCC by targeting PRDX1 both in vitro and in vivo.

Stemness-related gene signature for predicting therapeutic response in patients with esophageal cancer.

Background: Extensive research has indicated that tumor stemness promotes tumor progression. However, the underlying role of stemness-related genes (SRGs) in esophageal cancer (ESCA) remains unclear. Methods: This study identified differentially expressed stemness-related (DESR) messenger RNAs (mRNAs), microRNAs (miRNAs), and long non-coding RNAs (lncRNAs) in ESCA, and correlated them with the clinical features of patients with ESCA to develop a prognostic risk assessment model. Functional analysis, protein-protein interaction (PPI) analysis, competing endogenous RNA (ceRNA) networks, and tumor-infiltrating immune cell analyses were performed to corroborate the results obtained from the model. Results: Correlation analysis of the stemness enrichment scores revealed 1,106 DESR genes (DESRGs), 84 DESRmiRNAs, and 320 DESRlncRNAs were identified from The Cancer Genome Atlas Esophageal Carcinoma (TCGA-ESCA) dataset. Network clustering was performed and the top 20 connection points were identified, including CDC20 that connects to 136 adjacent nodes. A ceRNA network was constructed, including 17 DESRmiRNAs, 44 DESRlncRNAs, and 55 DESRGs. Conclusions: NCAPG [log2fold change (FC) =1.81; q value =2.68×10-11] was significantly upregulated in ESCA and positively correlated with resting natural killer (NK) cells, suggesting that human NK cells rest via the overexpression of NCAPG in ESCA. hsa-miR-1269a is significantly upregulated in ESCA patients with poor prognostic features. CD4+ resting memory T cells (P<0.01) were significantly negatively correlated with hsa-miR-1269a. The insights presented in this study will contribute to the development of innovative therapeutics for the treatment of patients with ESCA.

A retrospective study assessing the factors associated with visual outcome in retinal vein occlusion patients after anti-VEGF therapy.

BACKGROUND: Retinal vein occlusion (RVO) is one of the most frequent retinal vascular diseases. In this study, we aimed to investigate the predictive factors of visual outcome for RVO patients who underwent anti-vascular endothelial growth factor (VEGF) therapy. METHODS: RVO patients who underwent anti-VEGF treatment were recruited in this study from January 2018 to June 2020. Clinical data and optical coherence tomography (OCT) parameters were retrospectively reviewed. Best-corrected visual acuity (BCVA) was examined at baseline and after anti-VEGF therapy. Predictive factors associated with visual outcome were assessed by logistic regression model. Treatment-related adverse events were also recorded. RESULTS: The average logMAR BCVA was 0.91 at baseline and 0.70 at final examination (P = 0.003). Among 75 patients, 41 experienced visual improvement were categorized as group A, the remaining 34 patients without improved vision were categorized as group B. Patients in group A demonstrated better visual outcomes, including decreased logMAR BCVA (average logMAR BCVA: 0.53 in group A vs. 0.91 in group B, P < 0.001) and central retinal thickness (CRT) (average CRT: 230.88 µm in group A vs. 404.97 µm in group B, P < 0.001) after anti-VEGF treatment. Multivariable analysis showed that injection frequency (odds ratio [OR], 2.623; 95% confidence interval [CI], [1.282-5.366]), hypertension (odds ratio [OR], 0.189; 95% CI [0.044-0.811]), hyperlipemia (odds ratio [OR], 0.195; 95% CI [0.040-0.941]) and external limiting membrane (ELM) disruption (odds ratio [OR], 0.148; 95% CI [0.032-0.691]) were all significantly associated with the visual outcome of RVO patients who underwent anti-VEGF treatment. In general, anti-VEGF therapy was feasible for all RVO patients, though the response to anti-VEGF was suboptimal in certain patients. Prognostic factors including injection frequency, hypertension, hyperlipemia and ELM disruption may all be useful to provide predictive information of visual outcome of RVO patients in response to anti-VEGF treatment.

Sternal lifting increases the operating space in esophagectomy via mediastinoscopy: a prospective cohort study.

BACKGROUND: Esophagectomy with combined single-port inflatable mediastinoscopy and laparoscopy reduces the risk of postoperative respiratory complications as it obviates the need to pass through the pleural space. However, it has strict indications owing to the narrow space for operation. Therefore, we adopted a sternal lifting method using a retractor that enables the expansion of the operating space, a technique which has not been previously reported. We describe our experience and report the results of an evaluation of this new approach. METHODS: Thirty-nine patients with esophageal squamous cell carcinomas underwent esophagectomy using combined single-port inflatable mediastinoscopy and laparoscopy from March 2019 to August 2021. Among them, 20 cases received sternal suspension [sternal suspension group (SS group)], and 19 cases did not receive sternal suspension [non-sternal suspension group (NSS group)]. The short-term efficacy of the two groups was observed. RESULTS: Patients in the SS group had a shorter intramediastinal operation time (82.50 vs. 110.00 minutes; P<0.001), more dissected chest lymph nodes (14 vs. 12; P=0.036), and a lower incidence of postoperative hoarseness (2 vs. 6; P=0.235) than did those in the NSS group. There were no significant differences between the SS group and NSS group in terms of intraoperative blood loss, postoperative hospital stay, post-surgical pathologic TNM classification (pTNM), post-surgical pathologic tumor classification (pT), post-surgical pathologic extent of lymph node involvement (pN), and total number of dissected lymph nodes. There were no statistical differences in the incidence of anastomotic fistula, respiratory complications, arrhythmia, or chylothorax between the two groups. There was no mortality during hospitalization in the two groups. CONCLUSIONS: Sternal lifting increases the working space in esophagectomy via mediastinoscopy. It can make video-assisted radical esophagectomy by a transmediastinal approach with total pneumomediastinum assistance (VARETT) easier to perform, and sternal suspension in VARETT is safe and effective.

MicroRNA-155-5p promotes cell proliferation and invasion in lung squamous cell carcinoma through negative regulation of fibroblast growth factor 9 expression.

BACKGROUND: Non-small cell lung cancer (NSCLC) ranks first for mortality among all malignancies. Squamous cell carcinoma (SCC) is one of the main types of NSCLC. Previous studies have found that fibroblast growth factor 9 (FGF9) is closely related to lung SCC via different molecular regulatory mechanisms. This study aimed to explore the relationship between microRNA-155-5p (miR-155-5p) and FGF9 gene expression and their effects on the proliferation and invasion of lung SCC through experiments, in order to provide theoretical basis for overcoming this disease. METHODS: Fluorescence quantitative polymerase chain reaction was employed for the detection miR-155-5p and FGF9 expression in lung SCC tissues (n=40) and the corresponding adjacent normal tissues. The expression of FGF9 in the cancerous and adjacent tissues was detected by western blot. Transwell assay used to verify the effect of miR-155-5p on FGF-induced invasion and migration. Finally, subcutaneous tumor formation experiments in nude mice were used to verify how miR-155-5p and FGF9 affect the proliferative ability of lung SCC cells. RESULTS: The results of fluorescence quantitative PCR revealed that miR-155-5p and FGF9 were expressed at high and low levels, respectively, in lung SCC tissue samples relative to normal adjacent tissue samples. Western blot analysis of 6 lung SCC tissue samples revealed a significantly reduced level of FGF9. Correlation analysis uncovered that miR-155-5p and FGF9 share a significant negative correlation in lung SCC. At the messenger RNA and protein levels miR-155-5p could negatively regulate the expression of FGF9. Bioinformatics and dual luciferase reporter assay results confirmed FGF9 to be a downstream regulatory gene targeted by miR-155-5p. Our in vitro and in vivo results demonstrated that FGF9 overexpression exerted a significant inhibitory effect on miR-155-5p's ability to promote lung cancer cell growth, invasion, and proliferation. CONCLUSIONS: Our results show that miR-155-5p, as an oncogene, negative regulates FGF9 expression to promote SCC occurrence and development in the lungs.

Combined single-port transmediastinal and laparoscopic access with CO2 insufflation for esophageal resection: a case report on a canine model.

In order to be familiar with the dissection of the esophagus through a single transmediastinal access. Combined single-port transmediastinal and laparoscopic access with CO2 insufflation for esophageal resection were performed in experimental dogs. The esophagus was separated by single-hole mediastinoscopy, the stomach was separated by laparoscopy, and left neck anastomosis of tubular gastroesophagus was performed on the experimental dogs. Combined single-port transmediastinal and laparoscopic access with the CO2 insufflation is an alternative approach for esophagectomy with certain advantages compared to transthoracic approach. Animal models can help the surgeon get familiar with a certain procedure before transmediastinal esophagectomy on a human.

A Prospective Randomized Trial Comparing Jejunostomy and Nasogastric Feeding in Minimally Invasive McKeown Esophagectomy.

BACKGROUND: Early postoperative enteral nutrition is recommended for patients undergoing esophagectomy; however, the optimum method of tube feeding remains controversial. Thus, the aim of this study is to assess two common enteral nutrition methods after minimally invasive McKeown esophagectomy. METHODS: A randomized controlled trial was performed with 120 patients who underwent minimally invasive McKeown esophagectomy from January 2017 to December 2018. The patients were randomly divided so that 58 patients were in the jejunostomy feeding (JF) group and 62 patients were in the nasogastric feeding (NF) group. The postoperative outcomes, including complications, nutritional status, quality of life, and survival rate, were studied and used as the main parameters to compare the abovementioned tube feeding methods. RESULTS: The incidence of overall complications was equivalent between the two groups (P = 0.625), except for bowel obstruction (which occurred 4 times in the JF group but did not occur in the NF group). In the first month after surgery (postoperative month 1, POM1), a significantly higher body mass index (BMI) was observed in the JF group (23.6 ± 3.2) than in the NF group (20.9 ± 3.5, P = 0.032). The global quality-of-life scores were better in the JF group than in the NF group (P < 0.001). In addition, there were no significant differences between the two groups in terms of disease-free survival (DFS) (P = 0.816) and overall survival (OS) (P = 0.564). CONCLUSIONS: Compared with NF, JF provides more safety, efficacy, and utility as nutritional support for minimally invasive McKeown esophagectomy patients who have a high incidence of anastomotic leakage. However, the higher risk of intestinal obstruction after JF requires attention.

Knockdown of PDRG1 Could Inhibit the Wnt Signaling Pathway in Esophageal Cancer Cells.

OBJECTIVE: PDRG1, a short p53 and DNA damage-regulated gene, is overexpressed in many human tumors. This gene can promote proliferation and inhibit apoptosis in lung cancer. The aim of this study is to evaluate the effects of the PDRG1 gene on the Wnt signaling pathway in esophageal cancer cells. METHODS: In this study, 72 esophageal cancer tissues and adjacent normal tissues were collected, and the level of PDRG1 expression was assessed by quantitative real-time PCR (qRT-PCR). PDRG1 over-expression and knockdown cell lines (PDRG1o and PDRG1i) were established to analyze the effect of PDRG1 on esophageal cancer cells. RESULTS: The expression level of PDRG1 in esophageal cancer gradually increased with advanced TNM grades. PDRG1 knockdown can potentially promote apoptosis and inhibit the proliferation of esophageal cancer cells. Meanwhile, cisplatin chemosensitivity was enhanced by PDRG1 knockdown, via the suppression of cyclinD1 and ß-catenin expression within esophageal cancer cells. This indicates that PDRG1 silencing could inhibit the Wnt signaling pathway in esophageal cancer cells. CONCLUSION: Our data provides convincing evidence that PDRG1 may promote proliferation while inhibiting apoptosis and chemotherapy sensitivity in esophageal cancer cells.

Risk Analysis of Perioperative Death in Lung Transplant Patients With Severe Idiopathic Pulmonary Hypertension.

OBJECTIVE: To investigate the risk factors for perioperative mortality in patients with severe idiopathic pulmonary hypertension (IPAH) undergoing lung transplantation (LTx). METHODS: Twenty-two IPAH patients were included in the study and were divided 2 groups: a case group with early death post LTx (n = 5, 22.7%) and the remaining 17 recipients (87.3%), who did not die at perioperative time (the control group). All the preoperative clinical data and surgical procedures were analyzed using an independent t-test and Fisher's exact probability test. RESULTS: All the patients had over class III heart function rated by World Health Organization classification. Both groups had significantly reduced capacity of 6-min walking distance (6 MWD), decreased oxygen saturation, increased N-terminal probrain natriuretic peptide (NT-proBNP), certain frequent syncope, hemoptysis, and lower extremity edema. In addition, cardiac catheterization examination demonstrated that all patients had elevated pulmonary artery systolic pressure, mean pulmonary artery systolic pressure, and right atrial pressure. Furthermore, reduced mixed venous oxygen saturation and partial pressure of oxygen were seen in oxygen inhalation in a dose of 5 L/min in both groups. Cardiovascular morphological changes in both groups by cardiac ultrasonography included dilated diameter of the right ventricle and the main pulmonary artery. However, the right ventricular ejection fraction and stroke volume were notedly dropped. Distended inferior vena cava and enhanced frequency of hypertensive tricuspid regurgitation velocity response to stress were seen, and pericardial effusion was developed in both groups of patients. Nevertheless, a paired t-test (n = 5 vs n = 17) showed no significance between groups (P > .05), while there was a significant difference in frequencies of brief loss of consciousness (P < .01). Serum sodium concentration, cardiac index (CI), inner diameter of the left ventricle at end diastolic phase, and inner diameter ratio of RV/LV were 116.80 ± 5.76 mmol/L vs 29.88 ± 7.28 mmol/L (P = .002), 1.30 ± 0.07 L/min/m2 vs 1.58 ± 0.26 L/min/m2 (P = .030), 28.80 ± 3.70 mm vs 34.76 ± 5.43 mm (P = .033) and 1.81 ± 0.28 mmol/L vs 1.43 ± 0.26 (P = .011) between case and control group, respectively. CONCLUSIONS: All patients with IPAH waiting for lung transplantation were in critical condition. The highest death risks at perioperative time in IPAH patients were high frequencies of syncope, hyponatremia, lower CI, inner diameter of the left ventricle, and upward RV/LV ratio.