Reciprocal modulation of long noncoding RNA EMS and p53 regulates tumorigenesis.

p53 plays a central role in tumor suppression. Emerging evidence suggests long noncoding RNA (lncRNA) as an important class of regulatory molecules that control the p53 signaling. Here, we report that the oncogenic lncRNA E2F1 messenger RNA (mRNA) stabilizing factor (EMS) and p53 mutually repress each other's expression. EMS is negatively regulated by p53. As a direct transcriptional repression target of p53, EMS is surprisingly shown to inhibit p53 expression. EMS associates with cytoplasmic polyadenylation element-binding protein 2 (CPEB2) and thus, disrupts the CPEB2-p53 mRNA interaction. This disassociation attenuates CPEB2-mediated p53 mRNA polyadenylation and suppresses p53 translation. Functionally, EMS is able to exert its oncogenic activities, at least partially, via the CPEB2-p53 axis. Together, these findings reveal a double-negative feedback loop between p53 and EMS, through which p53 is finely controlled. Our study also demonstrates a critical role for EMS in promoting tumorigenesis via the negative regulation of p53.

Development and validation a nomogram for predicting new-onset postoperative atrial fibrillation following pulmonary resection.

BACKGROUND: The new-onset postoperative atrial fibrillation (NOPAF) following pulmonary resection is a common clinical concern. The aim of this study was to construct a nomogram to intuitively predict the risk of NOPAF and offered protective treatments. METHODS: Patients who underwent pulmonary resection between January 2018 and December 2020 were consecutively enrolled. Forward stepwise multivariable logistic regression analyses were used to screen independent predictors, and a derived nomogram model was built. The model performance was evaluated in terms of calibration, discrimination and clinical utility and validated with bootstrap resampling. RESULTS: A total of 3583 patients who met the research criteria were recruited for this study. The incidence of NOPAF was 1.507% (54/3583). A nomogram, composed of five independent predictors, namely age, admission heart rate, extent of resection, laterality, percent maximum ventilation volume per minute (%MVV), was constructed. The concordance index (C-index) was 0.811. The nomogram showed substantial discriminative ability, with an area under the receiver operating characteristic curve of 0.811 (95% CI 0.758-0.864). Moreover, the model shows prominent calibration performance and higher net clinical benefits. CONCLUSION: We developed a novel nomogram that can predict the risk of NOPAF following pulmonary resection, which may assist clinicians predict the individual probability of NOPAF and perform available prophylaxis. By using bootstrap resampling for validation, the optimal discrimination and calibration were demonstrated, indicating that the nomogram may have clinical practicality.

WDR63 inhibits Arp2/3-dependent actin polymerization and mediates the function of p53 in suppressing metastasis.

Accumulating evidence suggests that p53 plays a suppressive role in cancer metastasis, yet the underlying mechanism remains largely unclear. Regulation of actin dynamics is essential for the control of cell migration, which is an important step in metastasis. The Arp2/3 complex is a major nucleation factor to initiate branched actin polymerization that drives cell migration. However, it is unknown whether p53 could suppress metastasis through modulating Arp2/3 function. Here, we report that WDR63 is transcriptionally upregulated by p53. We show with migration assays and mouse xenograft models that WDR63 negatively regulates cell migration, invasion, and metastasis downstream of p53. Mechanistically, WDR63 interacts with the Arp2/3 complex and inhibits Arp2/3-mediated actin polymerization. Furthermore, WDR63 overexpression is sufficient to dampen the increase in cell migration, invasion, and metastasis induced by p53 depletion. Together, these findings suggest that WDR63 is an important player in the regulation of Arp2/3 function and also implicate WDR63 as a critical mediator of p53 in suppressing metastasis.

Long noncoding RNA EMS connects c-Myc to cell cycle control and tumorigenesis.

Deregulated expression of c-Myc is an important molecular hallmark of cancer. The oncogenic function of c-Myc has been largely attributed to its intrinsic nature as a master transcription factor. Here, we report the long noncoding RNA (lncRNA) E2F1 messenger RNA (mRNA) stabilizing factor (EMS) as a direct c-Myc transcriptional target. EMS functions as an oncogenic molecule by promoting G1/S cell cycle progression. Mechanistically, EMS cooperates with the RNA binding protein RALY to stabilize E2F1 mRNA, and thereby increases E2F1 expression. Furthermore, EMS is able to connect c-Myc to cell cycle control and tumorigenesis via modulating E2F1 mRNA stability. Together, these findings reveal a previously unappreciated mechanism through which c-Myc induces E2F1 expression and also implicate EMS as an important player in the regulation of c-Myc function.

Identified lung adenocarcinoma metabolic phenotypes and their association with tumor immune microenvironment.

BACKGROUND: Lung adenocarcinoma (LUAD), a subtype of non-small cell lung cancer (NSCLC), causes high mortality around the world. Previous studies have suggested that the metabolic pattern of tumor is associated with tumor response to immunotherapy and patient's survival outcome. Yet, this relationship in LUAD is still unknown. METHODS: Therefore, in this study, we identified the immune landscape in different tumor subtypes classified by metabolism-related genes expression with a large-scale dataset (tumor samples, n = 2181; normal samples, n = 419). We comprehensively correlated metabolism-related phenotypes with diverse clinicopathologic characteristics, genomic features, and immunotherapeutic efficacy in LUAD patients. RESULTS: And we confirmed tumors with activated lipid metabolism tend to have higher immunocytes infiltration and better response to checkpoint immunotherapy. This work highlights the connection between the metabolic pattern of tumor and tumor immune infiltration in LUAD. A scoring system based on metabolism-related gene expression is not only able to predict prognosis of patient with LUAD but also applied to pan-cancer. LUAD response to checkpoint immunotherapy can also be predicted by this scoring system. CONCLUSIONS: This work revealed the significant connection between metabolic pattern of tumor and tumor immune infiltration, regulating LUAD patients' response to immunotherapy.

Pulmonary artery pseudoaneurysm caused by a rare vascular tumor: epithelioid hemangioendothelioma.

We present a case of a 58-year-old female with a rare vascular tumor of intermediate malignancy. The initial manifestation was a pseudoaneurysm caused by the rupture of the right pulmonary artery after tumor invasion. The diagnosis of epithelioid hemangioendothelioma was confirmed by the morphologic and immunocytochemical features after surgery. The patient recovered smoothly and there has been no evidence of local recurrence or metastasis during the 2 years of follow-up.

[Establishment and Verification of Benign and Malignant Prediction Model of 
Subcentimeter Pulmonary Ground Glass Nodules Based on HRCT].

BACKGROUND: Pre-operative accuracy of subcentimeter ground glass nodules (SGGNs) is a difficult problem in clinical practice, but there are few clinical studies on the benign and malignant prediction model of SGGNs. The aim of this study was to help identify benign and malignant lesions of SGGNs based on the imaging features of high resolution computed tomography (HRCT) and the general clinical data of patients, and to build a risk prediction model. METHODS: This study retrospectively analyzed the clinical data of 483 patients with SGGNs who underwent surgical resection and were confirmed by histology from the First Affiliated Hospital of University of Science and Technology of China from August 2020 to December 2021. The patients were divided into the training set (n=338) and the validation set (n=145) according to 7:3 random assignment. According to the postoperative histology, they were divided into adenocarcinoma group and benign lesion group. The independent risk factors and models were analyzed by univariate analysis and multivariate Logistic regression. The receiver operator characteristic (ROC) curve was constructed to evaluate the model differentiation, and the calibration curve was used to evaluate the model consistency. The clinical application value of the decision curve analysis (DCA) evaluation model was drawn, and the validation set data was substituted for external verification. RESULTS: Multivariate Logistic analysis screened out patients' age, vascular sign, lobular sign, nodule volume and mean-CT value as independent risk factors for SGGNs. Based on the results of multivariate analysis, Nomogram prediction model was constructed, and the area under ROC curve was 0.836 (95%CI: 0.794-0.879). The critical value corresponding to the maximum approximate entry index was 0.483. The sensitivity was 76.6%, and the specificity was 80.1%. The positive predictive value was 86.5%, and the negative predictive value was 68.7%. The benign and malignant risk of SGGNs predicted by the calibration curve was highly consistent with the actual occurrence risk after sampling 1,000 times using Bootstrap method. DCA showed that patients showed a positive net benefit when the predictive probability of the predicted model probability was 0.2 to 0.9. CONCLUSIONS: Based on preoperative medical history and preoperative HRCT examination indicators, the benign and malignant risk prediction model of SGGNs was established to have good predictive efficacy and clinical application value. The visualization of Nomogram can help to screen out high-risk groups of SGGNs, providing support for clinical decision-making.

c-Myc-induced long noncoding RNA MIRE cooperates with hnRNPK to stabilize ELF2 mRNA and promotes clear cell renal cell carcinogenesis.

Elevated expression of c-Myc is associated with a variety of human cancers including clear cell renal cell carcinoma (ccRCC). Increasing evidence suggests that long noncoding RNAs (lncRNAs) are an important class of molecules that regulate both tumor initiation and progression. Here, we report the lncRNA c-Myc-induced regulator of ELF2 (MIRE) as a transcriptional target of c-Myc. MIRE functions as an oncogenic molecule in ccRCC by increasing ELF2 expression. Mechanistically, MIRE promotes phase separation of the RNA binding protein hnRNPK and facilitates the binding of hnRNPK to ELF2 mRNA, thereby resulting in the stabilization of ELF2 mRNA. Interestingly, MIRE is also under transcriptional control by ELF2, establishing an ELF2-MIRE positive feedback loop. Together, these findings provide new insights into the mechanisms by which c-Myc promotes tumorigenesis. They also implicate MIRE as an important regulator of ccRCC carcinogenesis.

MLF2 Negatively Regulates P53 and Promotes Colorectal Carcinogenesis.

Inactivation of the p53 pathway is linked to a variety of human cancers. As a critical component of the p53 pathway, ubiquitin-specific protease 7 (USP7) acts as a deubiquitinase for both p53 and its ubiquitin E3 ligase mouse double minute 2 homolog. Here, myeloid leukemia factor 2 (MLF2) is reported as a new negative regulator of p53. MLF2 interacts with both p53 and USP7. Via these interactions, MLF2 inhibits the binding of USP7 to p53 and antagonizes USP7-mediated deubiquitination of p53, thereby leading to p53 destabilization. Functionally, MLF2 plays an oncogenic role in colorectal cancer, at least partially, via the negative regulation of p53. Clinically, MLF2 is elevated in colorectal cancer and its high expression is associated with poor prognosis in patients with colorectal cancer. In wild-type-p53-containing colorectal cancer, MLF2 and p53 expressions are inversely correlated. These findings establish MLF2 as an important suppressor of p53 function. The study also reveals a critical role for the MLF2-p53 axis in promoting colorectal carcinogenesis.

Intelligent metasurface system for automatic tracking of moving targets and wireless communications based on computer vision.

The fifth-generation (5G) wireless communication has an urgent need for target tracking. Digital programmable metasurface (DPM) may offer an intelligent and efficient solution owing to its powerful and flexible controls of electromagnetic waves and advantages of lower cost, less complexity and smaller size than the traditional antenna array. Here, we report an intelligent metasurface system to perform target tracking and wireless communications, in which computer vision integrated with a convolutional neural network (CNN) is used to automatically detect the locations of moving targets, and the dual-polarized DPM integrated with a pre-trained artificial neural network (ANN) serves to realize the smart beam tracking and wireless communications. Three groups of experiments are conducted for demonstrating the intelligent system: detection and identification of moving targets, detection of radio-frequency signals, and real-time wireless communications. The proposed method sets the stage for an integrated implementation of target identification, radio environment tracking, and wireless communications. This strategy opens up an avenue for intelligent wireless networks and self-adaptive systems.

Continuous Serratus Anterior Plane Block Improved Early Pulmonary Function After Lung Cancer Surgical Procedure.

BACKGROUND: Serratus anterior plane block (SAPB) has been proven to be an efficient way to control postoperative pain. This study explored whether the use of continuous SAPB in combination with flurbiprofen could improve early pulmonary function in lung cancer patients undergoing video-assisted thoracoscopic surgery (VATS). METHODS: From July 2019 to April 2020, patients who scheduled for elective lung resection undergoing VATS were randomly allocated to receive patient-controlled SAPB in combination with intravenous flurbiprofen or patient-controlled intravenous analgesia. Postoperative pulmonary function variables, including forced expiratory volume in 1 second, and forced vital capacity were collected before and 24, 48, and 72 hours after Surgical Procedure. Pain intensity was measured at rest and on coughing. Comfort scores during breathing exercises, postoperative pulmonary complications, and adverse events were recorded. RESULTS: A substantial reduction in lung function was exhibited in both groups after Surgical Procedure (P < .001), but lung function variables in the continuous SAPB group were significantly higher (P < .001) throughout the postoperative period up to 72 hours, regardless of the surgical procedure type. Meanwhile, there were significant differences of pain intensity at rest and on coughing between the groups (P < .001). The incidence of pneumonia, pulmonary atelectasis, hypoxemia, vomiting, and the comfort score in the continuous SAPB group was significantly lower (P < .05). CONCLUSIONS: Postoperative acute pain treatment with continuous SAPB in combination with flurbiprofen enhanced pulmonary function and reduced postoperative pulmonary complications in lung cancer patients undergoing VATS.

The Comprehensive Analysis Identified an Autophagy Signature for the Prognosis and the Immunotherapy Efficiency Prediction in Lung Adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) is a fatal malignancy in the world. Growing evidence demonstrated that autophagy-related genes regulated the immune cell infiltration and correlated with the prognosis of LUAD. However, the autophagy-based signature that can predict the prognosis and the efficiency of checkpoint immunotherapy in LUAD patients is yet to be discovered. Methods: We used conventional autophagy-related genes to screen candidates for signature construction in TCGA cohort and 9 GEO datasets (tumor samples, n=2181; normal samples, n=419). An autophagy-based signature was constructed, its correlation with the prognosis and the immune infiltration of LUAD patients was explored. The prognostic value of the autophagy-based signature was validated in an independent cohort with 70 LUAD patients. Single-cell sequencing data was used to further characterize the various immunological patterns in tumors with different signature levels. Moreover, the predictive value of autophagy-based signature in PD-1 immunotherapy was explored in the IMvigor210 dataset. At last, the protective role of DRAM1 in LUAD was validated by in vitro experiments. Results: After screening autophagy-related gene candidates, a signature composed by CCR2, ITGB1, and DRAM1 was established with the ATscore in each sample. Further analyses showed that the ATscore was significantly associated with immune cell infiltration and low ATscore indicated poor prognosis. Meanwhile, the prognostic value of ATscore was validated in our independent LUAD cohort. GSEA analyses and single-cell sequencing analyses revealed that ATscore was associated with the immunological status of LUAD tumors, and ATscore could predict the efficacy of PD-1 immunotherapy. Moreover, in vitro experiments demonstrated that the inhibition of DRAM1 suppressed the proliferation and migration capacity of LUAD cells. Conclusion: Our study identified a new autophagy-based signature that can predict the prognosis of LUAD patients, and this ATscore has potential applicative value in the checkpoint therapy efficiency prediction.

[Application of laminated anastomosis with absorbable suture in cervical esophagogastrostomy].

OBJECTIVE: To observe the clinical results of laminated anastomosis using absorbable suture in cervical esophagogastrostomy, and to reduce the incidence of cervical esophagogastric anastomotic stricture. METHODS: A retrospective analysis was carried out on 210 patients who underwent cervical esophagogastrostomy after subtotal esophagectomy from January 2008 to June 2010. Among them, 96 cases were treated with traditional full layer interrupted varus suture (varus group) and the remaining 114 cases were treated with seromuscular layer and mucosal layer laminated anastomosis with absorbable suture (laminated group). Esophageal angiography was performed in 1 week, 1 month, and 3 months after the operation. The diameter of anastomatic stoma was measured on the anteroposterior and lateral angiography image respectively. The area of anastomatic stoma was calculated. The degree of stenosis was assessed according to the patients' dysphagia symptom. RESULTS: There was no operative deaths, no serious pulmonary complications and chylothorax, no sever esophageal reflux in all patients. The ratio of cervical esophagogastric anastomotic leakage was 2.1% (2/96) in the varus group. No anastomotic leakage in the laminated group. Compared with the varus group, the area of the anastomatic stoma in the laminated group was significantly increased in all measured time points (P<0.01). The incidence of obstruction in the laminated group was decreased significantly (P<0.01) in 1 month or in 3 months after operation compared with the varus group. CONCLUSION: Application of the laminated anastomosis with absorbable suture in cervical esophagogastrostomy can significantly reduce the incidence of anastomotic stenosis.

Tumor Immune Microenvironment Characteristics and Their Prognostic Value in Non-Small-Cell Lung Cancer.

INTRODUCTION: Cancer progression is determined not only by the malignant behavior of tumors but also by the immune microenvironment. The tumor immune microenvironment also plays a pivotal role in determining the clinical response of non-small-cell lung cancer (NSCLC) to immunotherapies. To understand the possible mechanisms and explore new targets in lung cancer immunotherapy, we characterized the immune profiles in NSCLC patients. METHODS: Seventy-one NSCLC patients who underwent radical resection were selected. The immune cell composition in paired tumor and adjacent normal lung tissues was tested by flow cytometry. The associations of tumor immune microenvironment characteristics with clinicopathological factors and overall survival were analyzed. Kaplan-Meier curves and Cox proportional hazards models were used to determine differences in survival. RESULTS: Compared with adjacent normal lung tissues, an increased proportion of CD45+ hematopoietic-derived cells, CD4+ T cell subtypes, Tregs and B cells was observed in tumor samples with a reduced frequency of myeloid cell populations. There was no significant increase in total CD8+ T cells, but both PD1+ and CD38+ CD8+ T cells were significantly enriched in tumor samples and statistically significantly associated with tumor size. In addition, positive CD38 expression was highly correlated with PD1 positivity. A high proportion of CD8+ T cells and a low percentage of PD1+ CD8+ T cells were statistically significantly associated with better survival in stage II and III patients, whereas a low frequency of CD38+ CD8+ T cells was statistically significantly associated with better survival in all patients and identified as an independent prognostic factor (p=0.049). CONCLUSION: We profiled the immune cells in the tumor tissues of NSCLC patients using flow cytometry. The results revealed significant enrichment of infiltrating immune cells. A strong correlation was identified between CD38 and PD-1 expression on CD8+ T cells in tumors. CD8+ T cells and their subtypes play a critical role in the prediction of prognosis.

Comparison of Perioperative Outcomes Between Precise and Routine Segmentectomy for Patients With Early-Stage Lung Cancer Presenting as Ground-Glass Opacities: A Propensity Score-Matched Study.

INTRODUCTION: Segmentectomy is widely used for early-stage lung cancer presenting as single or multiple ground-glass opacities (GGOs). Precise segmentectomy is the recommended procedure in China. However, clinically, most routine segmentectomies are performed using only high-resolution computed tomography (CT). The aim of this study was to evaluate the effect of two segmentectomy approaches for GGOs in the lung. METHODS: From January 2020 to September 2020, 55 precise segmentectomies performed with real-time guidance using 3D reconstruction and 343 routine segmentectomies for patients with single or multiple GGOs were performed as uniportal procedures. To reduce bias related to outcomes, preoperative clinical factors were used for propensity score matching (1:1); 55 precision and 55 routine segmentectomies were selected and further analyzed. Perioperative outcomes, namely operation time, blood loss, resection margins, number of removed lymph nodes, postoperative pulmonary function (1 month after surgery), length of postoperative stay, and postoperative complications were compared between the two groups. RESULTS: Patients constituted 43 men and 67 women, with an age range of 25-68 years (median: 53 years). No significant differences were seen between the groups regarding blood loss, complications, histological type, and postoperative pulmonary function, and there were no 30-day postoperative deaths in either group. The median operation time for the Precision group (74 min) was longer than in the Routine group (55 min) (p <0.01), and the number of removed lymph nodes in the Precision group (5 ± 1.1) was higher than in the Routine group (3 ± 0.8) (p <0.01). Chest tube duration days and postoperative stay days were similar in both groups; however, the rate of air leakage on postoperative day 1 was higher in the Precision group (p = 0.020). All patients in the Precision group had adequate resection margins. Four patients (7.3%) undergoing complex segmentectomy in the Routine group had inadequate resection margins and required resection of additional lung tissue. CONCLUSION: Routine segmentectomy can significantly shorten the operation time and might prevent postoperative air leakage in uniportal segmentectomy for lung GGOs. However, precision segmentectomy may be more precise for complex cases, ensuring adequate resection margins and lymph node dissection.

[Preoperative Pulmonary Nodule Localization Methods:A Comparison of Microcoil and Sclerosing Agent].

BACKGROUND: Small pulmonary nodules are usually difficult to identify during thoraco-scopic resection, and preoperative computed tomography (CT)-guided percutaneous puncture assisted localization can be helpful. The purpose of this study is to compare the localization effect and complication rates of two different methods by microcoil placement and sclerosing agent injection (Lauromacrogol). METHODS: A retrospective analysis of the clinical data of 371 patients with preoperative pulmonary nodules percutane us puncture localization was performed. According to the use of different materials, they were divided into the microcoil group (167 cases with 196 localized nodules ) and the sclerosing agent group (204 cases with 239 localized nodules). The localization effect, complication, pathological results and operation relates data were statistically analyzed. RESULTS: The localization failure rate (2.4%) was higher in the microcoil group than in the sclerosing agent group (0.5%) (P=0.011), and the localization time of sclerosing agent group was significantly shorter than the microcoil group [(18.78±6.91) min vs (11.99±3.77) min, P=0.000], but the distance between the selected localized nodules and the pleura was deeper in the microcoil group than in the sclerosing agent group [(9.59±8.62) mm vs (8.13±6.49)mm, P=0.002]. The overall complications in the microcoil group were significantly higher than those in the sclerosing agent group (P=0.000), in which pneumothorax was the most common. Through the analysis of related risk factors, we revealed that different positioning methods was independent risk factors. Wedge resection was the main type of surgical method and non-invasive carcinomas were the majority of postoperative pathological results. CONCLUSIONS: Our study suggests that both microcoil placement and sclerosing agent injection are suitable for preoperative pulmonary nodule localization equivalently, however, compared with microcoils placement, injection of lauromacrogol, the sclerosing agent, had lower failure rate, less complications, shorter localization time and it is worthy of promotion also by easy operation and low cost.

Value of N1 Lymph Node Examination in the Prognosis of Patients With pT1-3N0M0 Non-Small Cell Lung Cancer.

OBJECTIVE: This study aimed to analyze the relationship between the number of examined lymph nodes (ELNs) at the N1 station and the postoperative clinicopathological features and prognosis of patients with pT1-3N0M0 non-small cell lung cancer (NSCLC). METHODS: The cut-off value of the number of ELNs at the N1 station was obtained using X-tile software analysis. Kaplan-Meier survival curve analysis and the Cox proportional hazard model were used to study the impact of the number of ELNs at the N1 station on the prognosis of postoperative patients with pT1-3N0M0 NSCLC. RESULTS: The median survival time and 1-, 3- and 5-year survival rates of 0 ELNs at the N1 station were 28.0 months and 74.8%, 45.4%, and 21.2%, respectively. The median survival time and 1-, 3-, and 5-year survival rates of 1-4 ELNs at the N1 station were 45.0 months and 85.5%, 55.4%, and 39.1%, respectively. In the group with ≥ 5 ELNs at the N1 station, the median survival time and the 1-, 3- and 5-year survival rates were 59.0 months and 94.0%, 62.7%, and 48.2%, respectively. Both univariate and multivariate Cox regression analyses showed that the number of ELNs at the N1 station, T stage and operation type were independent factors affecting the prognosis of patients with pT1-3N0M0 NSCLC. CONCLUSION: Increasing the number of ELNs at the N1 station is positively correlated with the long-term survival rate of patients with T1-3N0M0 NSCLC. At least 5 LNs at the N1 station should be examined in pathological examination.

The hypermethylation of the CDKN2A and CHFR promoter region is a key regulatory mechanism of CDKN2A and CHFR expression in esophageal squamous cell carcinoma.

BACKGROUND: The aim of this study was to evaluate the correlation between CDKN2A and CHFR expression and the methylation status of the CpG island in the promoter region of esophageal squamous cell carcinoma (ESCC) cell lines, radioresistant ESCC cell lines and ESCC clinical tissue specimens. METHODS: To determine whether the methylation of CHFR and CDKN2A occurs in ESCC and enhanced in radioresistant ESCC cell lines, the DNA methylation of the following was analyzed by pyrosequencing and quantitative real-time polymerase chain reaction (PCR): (I) 28 ESCC tissues; (II) the ESCC cell lines KYSE-150 and KYSE-180; and (III) the radioresistant ESCC cell lines KYSE-150-radioresistance and KYSE-180-radioresistance. RESULTS: The methylation of CDKN2A and CHFR was found to be enhanced in the radioresistant ESCC cell lines KYSE-150-radioresistance and KYSE-180-radioresistance (P<0.05), and the expression of CDKN2A and CHFR was found to decrease correspondingly (P<0.05). The methylation of CDKN2A and CHFR was found to be higher in the ESCC tissue and paracarcinoma tissue than in the adjacent benign tissue. The overall survival rates for ESCC patients were significantly correlated with the levels of CDKN2A and CHFR expression (P<0.05). CONCLUSIONS: Our findings suggest that the hypermethylation of the CDKN2A and CHFR promoter region is a key regulatory mechanism of CDKN2A and CHFR expression in ESCC. Hypermethylated CDKN2A and CHFR are potential biomarkers for predicting the radioresistance of ESCC.

Correlation of pulmonary venous circulating tumor cells with clinicopathological parameters in patients with early-stage lung adenocarcinoma.

BACKGROUND: Tumor recurrence following the surgical resection of lung cancer (LCa) reduces long-term disease-free survival rates. This study aimed to investigate the association of pulmonary venous blood (PVB) circulating tumor cells (CTCs) with the clinicopathological features of patients with early-stage lung adenocarcinoma. METHODS: A total of 120 cases were enrolled, including 24 healthy controls, 36 patients with lung benign tumors, and 60 early-stage lung adenocarcinoma patients. Cells displaying a profile of human chromosome 8 specific sequence (CEP8)+/4',6-diamidino-2-phenylindole (DAPI)+/leukocyte-specific antibodies (CD45)‒ were regarded as CTCs, and counts of ≥2 CTCs per 3.2 mL of PVB were considered positive. The association of CTC counts with clinical parameters were analyzed. RESULTS: The number of CTCs were significantly higher in early-stage lung adenocarcinoma patients compared to benign or normal control group. Moreover, increased CTCs in lung adenocarcinoma was closely associated with tumor invasion, pathological staging and the epidermal growth factor receptor (EGFR) mutations (P<0.05), whereas no significant difference was observed between CTC counts and age, sex, smoking history, pathological cell morphology or immunohistochemical indicators (P>0.05). Univariate and multivariate Cox's proportional hazards regression confirmed that CTC counts were an independent indicator for the prediction of tumor invasion, pathological staging, and EGFR mutations. CONCLUSIONS: Our data suggest that CTC counts correlate with tumor invasion, pathological staging, and EGFR mutations. CTCs therefore represent promising biomarkers for the surveillance of lung adenocarcinoma progression.