Survival after Lung Metastasectomy from Urothelial Carcinoma: A Multi-Institutional Database Study.

BACKGROUND/OBJECTIVES: The efficacy of lung metastasectomy in patients with urothelial carcinoma remains inconclusive, as there is only limited evidence from small studies. In this study, we aimed to assess the prognostic outcomes of excising pulmonary metastases from urothelial carcinoma. METHODS: In this study, we utilized data from the Metastatic Lung Tumor Study Group of Japan database, a multi-institutional prospective database of pulmonary metastasectomies. We examined the data of patients who had undergone pulmonary metastasectomy for urothelial carcinoma between 1985 and 2021. Exclusion criteria included insufficient clinical information and follow-up of <3 months. RESULTS: The study cohort comprised 100 patients (63 bladder cancer, 37 renal pelvic and ureteral cancer), with a median follow-up of 34 months. There were 70 male and 30 female patients of average age 66.5 ± 10.4 years at lung metastasectomy. The median interval from treatment of the primary lesion to metastasectomy was 19 months and the maximum tumor diameter was 21 ± 15 mm. Three- and five-year overall survival rates were 69% and 59%, respectively. Three- and five-year disease-free survival rates were 56% and 46%, respectively. Multivariate analysis identified larger tumor diameter (hazard ratio: 1.62, 95% confidence interval: 1.21-2.17) and distant metastases at the time of treatment of the primary cancer (hazard ratio: 4.23; 95% confidence interval: 1.54-11.6) as significant adverse prognostic factors for overall survival. CONCLUSIONS: To our knowledge, this is the largest published case series of pulmonary resection for metastatic urothelial carcinoma, providing benchmark data for the assessment of long-term outcomes of this rare entity.

Detection of Circulating Tumor Cells and EGFR Mutation in Pulmonary Vein and Arterial Blood of Lung Cancer Patients Using a Newly Developed Immunocytology-Based Platform.

BACKGROUND: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors are powerful molecular targeted therapeutic agents for lung cancer. We recently developed an original immunocytology and glass slide-based circulating tumor cell (CTC) detection platform for both CTC enumeration and EGFR mutation analysis with DNA extracted from CTCs. METHODS: Using this platform, we conducted a pilot clinical study for CTC enumeration in peripheral blood (PB), pulmonary arterial blood (PA), and pulmonary venous blood (PV) from 33 patients with lung cancer (Stage I-III) who underwent surgery, followed by digital PCR-based EGFR mutation analysis of CTCs in PV from 12 patients. RESULTS: The results showed that CTC levels were significantly higher in PV and PA than in PB (p < 0.05, p < 0.01. respectively), with a notably greater number of small and large CTC clusters (p < 0.01). Genetic analysis of EGFR mutations of CTCs from PV (n = 12) revealed six mutations, including three Exon19del and three L856R, in CTCs and eight EGFR mutations, including five Exon19del and three L856R, in lung tumor tissue. CTC mutation status matched that of tissue samples in nine patients, was unmatched in two patients, and controversial in one patient, indicating a sensitivity of 0.75 (6/8) and specificity of 1.0 (4/4) with some false-negative results for the mutation analysis of CTCs. CONCLUSIONS: This immunocytology-based CTC detection platform is a convenient method for detecting both CTC number and EGFR mutation status under microscopy, suggesting its potential as a liquid biopsy tool in the hospital for patients with lung cancer in some clinical settings.

An effective plication technique for diaphragmatic eventration under thoracoscopy with laparoscopic image display.

Diaphragmatic eventration causes respiratory distress with the development of severe diaphragmatic compression of lung volume. While non-surgical treatment, such as physical therapy and pulmonary rehabilitation, is adequate for mild cases, surgical intervention is critical for severe diaphragmatic eventration. A 45-year-old man with respiratory fatigue was diagnosed with left diaphragmatic eventration and underwent surgery with diaphragmatic plication with double-row stapling under a video-assisted approach. Thoracoscopy with laparoscopic image display avoided visceral tissue involvement, and the double-stapling technique prevented diaphragmatic rupture and lowered the diaphragmatic level. The procedure improved the patient's respiratory function by reducing respiratory fatigue. This procedure is safe and effective for the thin and vulnerable diaphragmatic muscle.

Perioperative Evaluation of the Physical Quality of Life of Patients with Non-Small Cell Lung Cancer: A Prospective Study.

Surgery is the most effective treatment for early-stage lung cancer; however, it poses a higher physical burden than other treatment options. Therefore, understanding the perioperative course of patients is important. Using the Short Form Health Survey 36, we prospectively measured the physical quality of life of patients who underwent anatomical pulmonary resection for non-small cell lung cancer at Shonan Kamakura General Hospital, Kanagawa, Japan (n = 87). In the preoperative setting, patients who had lower performance status and lived alone had significantly worse physical quality of life scores on multivariate analysis (regression coefficient (95% confidence interval), -9.37 (-13.43--5.32) and -10.22 (-13.74--7.40), respectively, p < 0.0001 for both). At 6 months postoperatively, patients who stopped smoking within 1 year preoperatively (stopped smoking within 1 year vs. remote or never smokers, 41.0 ± 10.5 vs. 48.6 ± 7.2, p = 0.002), had lower performance status (0 vs. 1-2, 49.3 ± 6.6 vs. 38.6 ± 9.6, p < 0.0001), lived alone (living alone vs. living with somebody, 41.6 ± 9.7 vs. 48.1 ± 7.9, p = 0.021), and had higher comorbid burden (Charlson comorbidity index <3 vs. ≥3, 48.2 ± 6.9 vs. 39.1 ± 14.7, p = 0.003) had significantly worse physical quality of life scores on univariate analysis. More recent smoking (regression coefficient (95% confidence interval), -4.90 (-8.78-1.0), p = 0.014), lower performance status (8.90 (5.10-12.70), p < 0.0001), living alone (5.76 (1.39-10.13), p = 0.01), and higher comorbid burden (-6.94 (-11.78--2.10), p = 0.006) were significant independent predictors of worse postoperative physical quality of life on multivariate analysis. Therefore, patients with these conditions might need additional support to maintain their physical condition after anatomical lung cancer surgery.

Successful resection of a primary angiosarcoma of the azygos vein: A case report.

A 63-year-old woman was admitted to our department for the investigation of superior vena cava (SVC) syndrome. Computed tomography revealed an azygos tumor extending into the SVC. Video-assisted thoracic surgery (VATS) was performed to remove the distal end of the azygos vein in the left lateral position, followed by complete resection of the entire tumor under median sternotomy in the supine position. The histological diagnosis was a primary angiosarcoma of the azygos vein. The patient was discharged without any complications and is now alive and tumor-free 24 months after surgery. In addition, contrast-enhanced computed tomography revealed no graft occlusion in the two reconstructed brachiocephalic veins. Thoracoscopic surgery in the lateral position is useful for safe and reliable complete resection of a tumor arising from the azygos vein.

A Comparison of the Efficacies of OK-432 and Talc Slurry for Pleurodesis in Patients with Prolonged Air Leak after Pulmonary Resection.

PURPOSE: A prolonged air leak (PAL) is one of the common postoperative complications of pulmonary resection. The aim of this study was to evaluate the efficacy and safety of pleurodesis with sterile talc or OK-432 for postoperative air leak. METHODS: Patients with postoperative air leak who received chemical pleurodesis using sterile talc or OK-432 were retrospectively identified from medical records data. For pleurodesis with either agent, prior assessment and approval by the hospital safety department were carried out for each case, in addition to individual consent. RESULTS: Between February 2016 and June 2022, 39 patients had PALs and underwent chemical pleurodesis. Among them, 24 patients received pleurodesis with talc (Talc group) and 15 with OK-432 (OK-432 group). The leak resolved after less than two pleurodesis treatments in 22 patients (91.7%) in the Talc group compared with 14 patients (93.3%) in the OK-432 group. Pleurodesis significantly increased white blood cell counts, C-reactive protein concentration, and body temperature in the OK-432 group compared with that in the Talc group (p <0.001, p = 0.003, and p <0.001, respectively). CONCLUSIONS: Pleurodesis with talc may be an effective treatment option for postoperative air leak. Our findings suggest that talc was as effective as OK-432 and resulted in a milder systemic inflammatory response.

Arterial Embolization and Cone-Beam Computed Tomography-Guided Lung Resection for Anomalous Systemic Arterial Blood Supply to Normal Lung: Two Case Reports.

Systemic arterial blood supply to a normal lung is a rare anatomical abnormality. Surgery is usually indicated because this abnormality leads to pulmonary hypertension. Herein, we report our experience and ideas for safe vessel dissection. Case 1 was a woman in her 50s. We performed a left lower lobectomy following percutaneous coil embolization. The aberrant artery with emboli was confirmed intraoperatively by cone-beam computed tomography (CBCT) to safely dissect under thoracoscopic surgery (TS). Case 2 was a man in his 40s. Following percutaneous endovascular plug occlusion, we performed a left partial resection using indocyanine green fluorescence navigation. Intraoperatively, CBCT imaging demonstrated the aberrant artery and exact position of the emboli. This combination technique of interventional radiology and TS with CBCT imaging was considered safe and more secure for the treatment of anomalous systemic arterial blood supply to a normal lung.

Survival after Lung Metastasectomy from Esophageal Cancer: Results from a Multi-Institutional Database.

To clarify the clinical impact and to identify prognostic predictors of surgical intervention for pulmonary metastasis from esophageal cancer, a registry database analysis was performed. From January 2000 to March 2020, patients who underwent resection of pulmonary metastases from primary esophageal cancer at 18 institutions were registered in a database developed by the Metastatic Lung Tumor Study Group of Japan. An amount of 109 cases were reviewed and examined for the prognostic factors for pulmonary metastasectomy of metastases from esophageal cancer. As a result, five-year overall survival after pulmonary metastasectomy was 34.4% and five-year disease-free survival was 22.1%. The multivariate analysis for overall survival revealed that initial recurrence site, maximum tumor size, and duration from primary tumor treatment to lung surgery were selected as the significant prognostic factors (p = 0.043, p = 0.048, and p = 0.037, respectively). In addition, from the results of the multivariate analysis for disease free survival, number of lung metastases, initial recurrence site, duration from primary tumor treatment to lung surgery, and preoperative chemotherapy for lung metastasis were selected as the significant prognostic factors (p = 0.037, p = 0.008, p = 0.010, and p = 0.020, respectively). In conclusion, eligible patients with pulmonary metastasis from esophageal cancer selected based on the identified prognostic predictors would be good candidates for pulmonary metastasectomy.

Cytological features of stromal spindle cells and their prognostic significance in lung adenocarcinoma.

INTRODUCTION: Cancer-associated fibroblasts (CAFs) in the tumour microenvironment play a key role in tumour development, proliferation, invasion, and metastasis. The cytological features of spindle cells including CAFs-defined as stromal spindle cells (SSCs) adjacent to cancer cells-are frequently encountered in pulmonary adenocarcinomas. This study aimed to investigate the association between the presence of SSCs in cytological specimens and the clinicopathological features. METHODS: We evaluated 211 patients with pulmonary adenocarcinoma who underwent surgical resection. All participants had cytological specimens corresponding to the histological specimens available for review. RESULTS: Of the 211 cases examined, 89 were SSC-positive (SSC+ ) and 122 were SSC-negative (SSC- ). SSC+ cases were more frequently associated with higher pathological stage (P < 0.001), lymph node metastasis (P = 0.002), anaplastic lymphoma kinase (ALK) gene rearrangement (P = 0.04), high tumour grade (P < 0.001), solid and micropapillary predominant pattern (P = 0.02), and lymphatic vessel (P = 0.003), blood vessel (P < 0.001), and pleural invasion (P = 0.03) as compared to SSC- cases. Patients with SSC+ adenocarcinoma had a significantly shorter recurrence-free survival than those with SSC- adenocarcinoma (P = 0.009). Cytologically, necrotic background (P = 0.002), mucinous cancer cells (P = 0.02), pleomorphic cells (P < 0.001), and mutual cell inclusions (P = 0.01) were observed more frequently in SSC+ adenocarcinomas. CONCLUSIONS: The presence of SSCs could be an important cytological feature for predicting poor prognosis in lung adenocarcinomas.

Solitary pulmonary capillary hemangioma mimicking a preinvasive malignant lesion in an asymptomatic middle-aged female patient.

Pulmonary capillary hemangiomatosis (PCH) is a rare disease characterized by a proliferation of capillaries in the alveolar septa, bronchial and venous walls, pleura, and regional lymph nodes. However, the etiology of the disease remains unknown due to its rarity. Therefore, we present a case of a solitary PCH lesion without symptoms in a 38-year-old female patient. According to computed tomography, she was diagnosed with lung carcinoma, indicated by a tiny nodule with ground-glass opacity detected in her right upper lung. However, no other lesions were detected on systemic examination. Consequently, partial lung resection was conducted, since the lesion was suspected of lung adenocarcinoma. Pathologic results showed that the thick alveolar septa were caused by capillary growth without cellular atypia and hardly any infiltration of inflammatory cells. Finally, we diagnosed the pulmonary lesion as PCH, although solitary PCH has previously been reported in a few case reports. Therefore, further case studies are essential to clarify the causes of PCH.

Optimal Chest Drainage Method After Anatomic Lung Resection: A Prospective Observational Study.

BACKGROUND: Several methods for chest drainage after pulmonary resection of malignant lung tumors exist, but consensus on the ideal method has not been reached. METHODS: We conducted a multicenter prospective observational study. We enrolled 2200 patients who underwent lung resection for lung tumors. Of the 1470 patients who underwent anatomic resection, 347 showed air leak on the morning of postoperative day 1. They were assigned to 3 groups according to the chest drainage method on postoperative day 1. RESULTS: Of 347 patients with postoperative air leaks, 107 (30.8%), 179 (51.6%), and 61 (17.6%) were assigned to water seal, continuous suction, and digital drainage, respectively. The median postoperative air leak duration was significantly longer with digital drainage (4.0 days) than with either water seal (2.5 days) or continuous suction (3.0 days; P = .009). Chest tubes were required for significantly more days on average with digital drainage (6.0 days) than with water seal (4.0 days) or continuous suction (4.0 days; P = .003). Prolongation of air leak duration was significantly more likely to occur in patients with body mass index <18.5 kg/m2 (hazard ratio [HR], 1.6; 95% CI, 1.1-2.3), moderate or severe air leak on postoperative day 1 (HR, 2.0; 95% CI, 1.5-2.6), or digital drainage (HR, 1.4; 95% CI, 1.01-1.9). CONCLUSIONS: Water seal was associated with significantly shorter duration of postoperative air leak and chest drainage compared with continuous suction and digital drainage.

Expert consensus on indocyanine green fluorescence imaging for thoracoscopic lung resection (The Version 2022).

The use of the white-light thoracoscopy is hampered by the low contrast between oncologic margins and surrounding normal parenchyma. As a result, many patients with in situ or micro-infiltrating adenocarcinoma have to undergo lobectomy due to a lack of tactile and visual feedback in the resection of solitary pulmonary nodules. Near-infrared (NIR) guided indocyanine green (ICG) fluorescence imaging technique has been widely investigated due to its unique capability in addressing the current challenges; however, there is no special consensus on the evidence and recommendations for its preoperative and intraoperative applications. This manuscript will describe the development process of a consensus on ICG fluorescence-guided thoracoscopic resection of pulmonary lesions and make recommendations that can be applied in a greater number of centers. Specifically, an expert panel of thoracic surgeons and radiographers was formed. Based on the quality of evidence and strength of recommendations, the consensus was developed in conjunction with the Chinese Guidelines on Video-assisted Thoracoscopy, and the National Comprehensive Cancer Network (NCCN) guidelines on the management of pulmonary lesions. Each of the statements was discussed and agreed upon with a unanimous consensus amongst the panel. A total of 6 consensus statements were developed. Fluorescence-guided thoracoscopy has unique advantages in the visualization of pulmonary nodules, and recognition and resection of the anterior plane of the pulmonary segment. The expert panel agrees that fluorescence-guided thoracoscopic surgery has the potential to become a routine operation for the treatment of pulmonary lesions.

[Traumatic Lung Injury].

Thoracic injuries are significant causes of morbidity and mortality in trauma patients. Traumatic pulmonary contusion and/or laceration are often observed in patients with chest trauma, explosion injuries or a shock wave associated with penetrating trauma. A pulmonary contusion is an injury to the lung parenchyma without actual structural damage. As a result of damage to alveoli and capillaries, it results in leakage of blood and other interstitial fluids across the alveolar-capillary membrane into lung tissue and alveolar space. Since oxygenated air can not enter into fluid-filled alveoli, hypoventilation and decreased perfusion by reflux vasoconstriction result in hypoxemia and hypercapnia. Pulmonary laceration is a lung injury with disruption of the architecture of the lung, while pulmonary contusion does not. There is almost always concurrent pulmonary contusion, and pneumothorax, hemothorax, or hemopneumothorax. In addition, pulmonary laceration can be a cause of forming a cyst or hematoma, which usually disappears over a period of weeks or months. However, pneumatocele can occur in some cases when lacerations are enlarged with air-filled cavity. It is important for thoracic surgeons to understand pathophysiology of traumatic lung injury, and to know the diagnosis and treatment.

A pilot study of intraoperative localization of peripheral small pulmonary tumors by cone-beam computed tomography: sandwich marking technique.

Background: Intraoperative identification of small pulmonary nodules has been an important technical issue. We aimed to develop a new localization method which is much safer and simple procedure compared with conventional methods. Methods: This was a retrospective study including patients with resected peripheral pulmonary nodules between November 2017 and April 2021 at Teikyo University School of Medicine, and Saitama Cardiovascular and Respiratory Center. All surgical procedure was wedge resection, and the tumor size was equal to or less than 20 mm which were detected by cone-beam computed tomography (CBCT; Philips Allura Xper FD 20, Philips). Some metal clips were put on several places of visceral pleura, where the target lesion was sandwiched by marking clips (sandwich marking technique). CBCT detected both the target lesion and metal clips, and video-assisted thoracoscopic surgery (VATS) was performed. Radiological and pathological findings were analyzed, and the correlation coefficient of tumor size was examined among pre-, intra-, and post-operative tumor sizes. Results: The average age of 90 patients was 65.2 years, and 47 were male (52.2%). All procedure was wedge resection including twelve bi-wedge resections, and one hundred nine peripheral pulmonary lesions were obtained by sandwich marking technique. The detection rate was 100%, and there was no marking-related complication. Conclusions: All small peripheral pulmonary lesions were successfully detected and resected by using CBCT with no marking-related complication. Sandwich marking technique was demonstrated to provide safe, reliable, and simple localization procedure for small peripheral pulmonary lesions.

Positive Intrapleural Pressure with Carbon Dioxide May Limit Intraoperative Pulmonary Arterial Bleeding: Verification by Animal Model.

PURPOSE: Intraoperative complications, especially unexpected bleeding, are of great concern in the safety of thoracoscopic surgery. We investigated the hemostatic efficacy and safety of positive intrapleural pressure (PIP) with carbon dioxide insufflation by assessing the amount of blood loss in a pulmonary arterial hemorrhage model. METHODS: An ex vivo experimental model of saline flow into a swine vessel was created in a container simulating a chest cavity. From the results, in vivo experiments (swine model) were conducted to compare the pulmonary arterial bleeding volume while applying PIP. RESULTS: In the ex vivo experiment, regardless of the incision type, the outflow volumes did not significantly differ at flow pressures of 20, 30, and 40 mmHg. At each flow pressure, the outflow volumes at 10, 15, and 20 mmHg of positive pressure in the container were significantly smaller than those of the control (p = 0.027, p = 0.002, and p = 0.005, respectively). Similarly, the in vivo experiments showed that bleeding decreased as intrapleural pressure increased (slope = -0.22, F = 55.13, p <0.0001). CONCLUSION: It may be possible to temporarily suppress pulmonary arterial bleeding by increasing the intrapleural pressure to 10 to 20 mmHg using carbon dioxide insufflation. This method may be an adjunctive hemostatic maneuver for intraoperative bleeding.

Loop-Mediated Isothermal Amplification as Point-of-Care Testing for EGFR-Mutated Lung Adenocarcinoma.

Liquid biopsy has been adapted as a diagnostic test for EGFR mutations in patients with advanced or metastatic non-small cell lung cancer (NSCLC). Loop-mediated isothermal amplification (LAMP) has been widely used for the rapid detection of pathogens through DNA amplification. This study investigated the efficacy of an EGFR-LAMP assay using plasma samples of patients with resected NSCLC tumors. The EGFR status was investigated using both LAMP and next-generation sequencing (NGS) assays in cases that met the following criteria: (1) pulmonary adenocarcinoma with EGFR mutation detected by the Therascreen EGFR PCR Kit and (2) preoperative plasma samples contained enough DNA for the LAMP and NGS experiments. Among 51 specimens from patients with EGFR-mutated tumors or metastatic lymph nodes, the LAMP assay detected 1 EGFR mutation that was also detected in the NGS assay. However, a plasma sample that demonstrated EGFR wild type in the LAMP assay showed an EGFR mutant status in NGS. The detection rates (1.9% in LAMP and 3.9% in NGS) were very low in both assays, demonstrating a similar performance in detecting EGFR mutations in NSCLC tumors; therefore, it could be a more suitable test for the advanced stage, not the early stage. Notably, the LAMP assay was more time-saving, cost-effective, and straightforward. However, further investigation is required to develop a more sensitive assay.

Oncological issues in staging mediastinal lymph node metastasis for left lung cancer.

OBJECTIVE: We aimed to discuss the underlying oncological issues in staging of mediastinal lymph node metastasis in patients with left lung cancer who underwent extended radical lymphadenectomy (ERL). METHODS: This multi-institutional retrospective study analyzed 116 patients with left non-small-cell lung cancer who underwent bilateral paratracheal lymph node dissection (ERL) via median sternotomy. The clinicopathological records of patients with mediastinal lymph node metastasis were examined for prognostic factors, including age, sex, histology, tumor size, cN number, preoperative data, metastatic stations (number and distribution), pT, and adjuvant chemotherapy. RESULTS: Mediastinal lymph node metastases were found in 43 patients, and right paratracheal lymph node metastases (pN3) were found in 13 patients. The 5-year overall survival rate was 25.2% in patients with pN3 tumors (n = 13) and 23.1% in patients with pN2 tumors (n = 30). The prognosis did not differ between patients with pN3 and pN2. Univariate analyses showed that histology, cN, and adjuvant chemotherapy were significant prognostic factors in patients with mediastinal lymph node metastasis. In these 43 patients, cN and adjuvant chemotherapy were significant independent prognostic factors in multivariate analysis. CONCLUSIONS: The prognostic factors for left lung cancer with mediastinal lymph node metastasis were cN status and adjuvant chemotherapy, and not pN status (pN2 or pN3). We hope that the study results, which suggest that there may be no difference in prognosis between pN2 and pN3, would broaden the discussion of oncological issues in the staging of mediastinal lymph node metastasis of left lung cancer.

A novel method of tracheal anastomosis healing using a single submucosal injection of basic fibroblast growth factor: initial report.

OBJECTIVES: For the technical management of tracheal anastomosis, developing new and simple methods is required to relieve anastomotic tension. This study aimed to investigate whether basic fibroblast growth factor (bFGF) only once injected immediately before anastomosis promotes cartilage regeneration at the tracheal anastomosis and whether the regenerated cartilage has the effect of reinforcing the anastomosis in a rabbit model. METHODS: New Zealand white rabbits were anaesthetized, and the cervical trachea was exposed through a cervical midline incision, followed by resection of the 10th tracheal cartilage. The rabbits were categorized into 2 groups: the bFGF group (n = 6) and the control group (n = 6). In the former group, bFGF (25 µg) was administered into the submucosal layer of the cartilage using a 27-G needle immediately before tracheal anastomosis. The animals were sacrificed 4 weeks later. Histological, mechanical and biochemical evaluations were performed on this anastomosed trachea. RESULTS: At 4 weeks of age, the anastomoses were spindle-shaped and displayed maximum diameter at the injection site compared with those in the control group. Histological evaluation showed that cartilage tissue had regenerated between the 9th and 11th tracheal cartilage rings. Tensile test showed that the anastomoses displayed a significantly high strain/stress ratio (P = 0.035). The collagen type II and glycosaminoglycan levels were significantly increased, and the collagen type I level was significantly decreased (P = 0.019, P = 0.013 and P = 0.045, respectively). CONCLUSIONS: A new wound-healing concept of airway anastomosis could be provided by the results that single injection of bFGF regenerated tracheal cartilage in rabbits and strengthened the anastomosis by bridging the regenerated and well-matured cartilage. Further investigation of this method will lead to potential clinical applications for reinforcement of tracheal anastomoses.

COL11A1 promotes esophageal squamous cell carcinoma proliferation and metastasis and is inversely regulated by miR-335-5p.

BACKGROUND: Esophagus squamous cell carcinoma (ESCC) is a sort of cancer that occurs in the esophageal epithelial tissue. This study performed integrated bioinformatics analysis of Gene Expression Omnibus (GEO) datasets GSE32424, GSE29968, and GSE130078. Collagen type XI alpha 1 (COL11A1) was identified as the hub gene in ESCC progression. The involvement of COL11A1 in ESCC development was next determined using in vitro functional tests. METHODS: Hub genes were identified through integrated bioinformatics analysis. The real-time reverse transcription-polymerase chain reaction was implemented for detecting the expression of COL11A1 mRNA in esophageal cancer cells. KYSE-30 cells were transfected using a vector encoding COL11A1. The proliferation of cells was determined using the Cell Counting Kit-8 (CCK-8) assay. Detection of the cell migration and invasion was made through making use of the transwell test. The development of ESCC cells in vivo was evaluated in naked mice. The interplay among COL11A1 and microRNA-335-5p (miR-335-5p) was discovered using a luciferase reporter experiment. RESULTS: In vitro studies showed the upregulation of COL11A1 in ESCC cell lines obtained from ESCC patients and upregulation of COL11A1 was correlated with poor disease-free survival of ESCC patients, thereby implying an oncogenic involvement of COL11A1 in ESCC. Overexpression of COL11A1 enhanced the proliferation of ESCC cells, invasion, and migration; whereas COL11A1 knockdown impeded the proliferation of ESCC cells, invasion, and migration. Additionally, miRNA pathway analysis in combination with TargetScan's online prediction and the luciferase reporter assay suggested miR-335-5p targeting and negatively regulating the COL11A1 3' untranslated region (3'UTR) within ESCC cells. MiR-335-5p overexpression diminished the development of ESCC cells. Additionally, co-expression of COL11A1 ameliorated the repressive influence of miR-335-5p overexpression on the growth and metastasis of ESCC cells. CONCLUSIONS: Using comprehensive bioinformatics analysis, the current study identified COL11A1 as an oncogene in ESCC. The mechanistic studies indicated that COL11A1 promoted ESCC cell progression and that miR-335-5p negatively regulated the expression of COL11A1 in ESCC.