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1.
Artigo em Inglês | MEDLINE | ID: mdl-34729628

RESUMO

PURPOSE: A novel cystine-knot peptide-based PET radiopharmaceutical, 18F-FP-R01-MG-F2 (knottin), was developed to selectively bind to human integrin αvß6 which is overexpressed in pancreatic cancer. The purpose of this study is to evaluate the safety, biodistribution, dosimetry, and lesion uptake of 18F-FP-R01-MG-F2 in patients with pancreatic cancer. METHODS: Fifteen patients (6 men, 9 women) with histologically confirmed pancreatic cancer were prospectively enrolled and underwent knottin PET/CT between March 2017 and February 2021 (ClinicalTrials.gov Identifier NCT02683824). Vital signs and laboratory results were collected before and after the imaging scans. Maximum standardized uptake values (SUVmax) and mean SUV (SUVmean) were measured in 24 normal tissues and pancreatic cancer lesions for each patient. From the biodistribution data, the organ doses and whole-body effective dose were calculated using OLINDA/EXM software. RESULTS: There were no significant changes in vital signs or laboratory values that qualified as adverse events or serious adverse events. At 1 h post-injection, areas of high 18F-FP-R01-MG-F2 uptake included the pituitary gland, stomach, duodenum, kidneys, and bladder (average SUVmean: 9.7-14.5). Intermediate uptake was found in the normal pancreas (average SUVmean: 4.5). Mild uptake was found in the lungs and liver (average SUVmean < 1.0). The effective dose was calculated to be 2.538 × 10-2 mSv/MBq. Knottin PET/CT detected all known pancreatic tumors in the 15 patients, although it did not detect small peri-pancreatic lymph nodes of less than 1 cm in short diameter in two of three patients who had lymph node metastases at surgery. Knottin PET/CT detected distant metastases in the lungs (n = 5), liver (n = 4), and peritoneum (n = 2), confirmed by biopsy and/or contrast-enhanced CT. CONCLUSION: 18F-FP-R01-MG-F2 is a safe PET radiopharmaceutical with an effective dose comparable to other diagnostic agents. Evaluation of the primary pancreatic cancer and distant metastases with 18F-FP-R01-MG-F2 PET is feasible, but larger studies are required to define the role of this approach. TRIAL REGISTRATION: NCT02683824.

2.
Oncol Lett ; 22(6): 851, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34733369

RESUMO

Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1 (PLOD1) is an enzyme that catalyzes the hydroxylation of lysyl residues in collagen-like peptides, and is responsible for the stability of intermolecular crosslinks. High PLOD1 mRNA levels have been determined to be prognostically significant in numerous human malignancies. The objective of the present study was to elucidate the pathological mechanism of PLOD1 in lung cancer. The expression status and prognostic value of PLOD1 in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSA) were investigated using Gene Expression Profiling Interactive Analysis (GEPIA). Cell Counting Kit 8 and colony formation assays were performed to assess the impact of PLOD1 depletion and overexpression on the proliferation and colony formation abilities of the A549 lung cancer cell line. Luciferase reporter assays were used to clarify whether E2F transcription factor 1 (E2F1) was a downstream target of PLOD1 in lung cancer. Finally, the correlations between PLOD1 expression and a typical central downstream effector molecule of E2F1 signaling were determined using cBioportal. The GEPIA datasets revealed that PLOD1 mRNA levels were upregulated in LUAD and LUSC samples. Furthermore, the overexpression of PLOD1 promoted cancer cell proliferation and colony formation in vitro, while PLOD1-knockout produced the opposite effect. Notably, PLOD1 markedly induced the transcriptional activity of E2F1. Additionally, the expression of PLOD1 was significantly correlated with that of H2A histone family member X. In conclusion, the findings of the present study indicate that PLOD1 promoted lung cancer through E2F1 activation, and proposed a rationale for targeting the PLOD1/E2F1 axis to treat lung cancer.

4.
J Cell Mol Med ; 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34716659

RESUMO

N6 -methyladenosine (m6 A) is the most prevalent modification in mRNA and engages in multiple biological processes. Previous studies indicated that m6 A methyltransferase METTL3 ('writer') and demethylase FTO ('eraser') play critical roles in heart-related disease. However, in the heart, the function of m6 A 'reader', such as YTH (YT521-B homology) domain-containing proteins remains unclear. Here, we report that the defect in YTHDC1 but not other YTH family members contributes to dilated cardiomyopathy (DCM) in mice. Cardiac-specific conditional Ythdc1 knockout led to obvious left ventricular chamber enlargement and severe systolic dysfunction. YTHDC1 deficiency also resulted in the decrease of cardiomyocyte contractility and disordered sarcomere arrangement. By means of integrating multiple high-throughput sequence technologies, including m6 A-MeRIP, RIP-seq and mRNA-seq, we identified 42 transcripts as potential downstream targets of YTHDC1. Amongst them, we found that Titin mRNA was decorated with m6 A modification and depletion of YTHDC1 resulted in aberrant splicing of Titin. Our study suggests that Ythdc1 plays crucial role in regulating the normal contractile function and the development of DCM. These findings clarify the essential role of m6 A reader in cardiac biofunction and provide a novel potential target for the treatment of DCM.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34657366

RESUMO

Hypertension was one common comorbidity of knee osteoarthritis (KOA), but the effect of different types of antihypertensive drugs on pain and joint space width (JSW) was unclear and not compared. Four hundred ninety KOA patients using one of the beta-blockers, ACE inhibitors, angiotensin receptor blockers, Calcium channel blockers (CCBs), or thiazide diuretics were followed for four years. The blood pressure, cumulative knee replacement rate, Womac pain, and JSW were compared among groups. All data were from the Osteoarthritis Initiative project. The CCBs group has the highest systolic blood pressure, replacement rate, and pain score at most visit timepoints. At baseline, the CCBs group was with significantly higher pain score than the beta-blockers group (3.3 vs 1.3, p < .05), the angiotensin receptor blockers group (3.3 vs 1.4, p < .05), and the thiazide diuretics group (3.3 vs 1.6, p < .05) in male; the CCBs group was with significantly higher pain score than the beta-blockers group (3.8 vs 2.0, p < .01), and the angiotensin receptor blockers group (3.8 vs 2.2, p < .05) in female. The results of females at 36 months were similar to the baseline. Among the common antihypertensive drugs, CCBs were associated with high replacement rates, high pain scores, and less JSW in KOA patients.

7.
ACS Appl Mater Interfaces ; 13(43): 51608-51617, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34677931

RESUMO

Graphene nanowall (GNW) films, a representation of three-dimensional (3D) carbon nanomaterial films, are emerging as promising candidates for applications in electric devices and composites, on account of their 3D structures and exceptional properties of graphene sheets. However, the frictional responses of GNW films, which exhibit significant influence on their performances, have seldom been reported. Herein, we reported a growth process of a GNW film by the chemical vapor deposition method and studied the frictional behavior of the GNW film for the first time. The results demonstrated the nonlinearity between the frictional force of the GNW film and normal load. Based on the structural evolution of the GNW film with normal load and frictional tests on precompressed GNW films, the influence of the strain property of the GNW film, namely, the strengthening effect, could be confirmed. The results of molecular dynamics simulations show that the bending force of GNWs in front of the tip plays a determinate role in the frictional force of the GNW film. Furthermore, the bending force is proportional to the bending contact area, which increases nonlinearly with the normal load due to the strengthening effect of the GNW film. The result suggests that the nonlinear increase of the bending contact area induced by the strengthening effect of the GNW film is the key factor that leads to its nonlinear frictional force. This study provides a novel insight into the frictional responses of GNW films, which would be beneficial for the design and application of electric devices and composites made of GNW and other 3D carbon nanomaterial films.

9.
J Orthop Surg Res ; 16(1): 635, 2021 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-34689823

RESUMO

BACKGROUND: Although the high offset Tri-Lock bone preservation stem (BPS) was used widely, few studies explored the clinical and radiological results. The purpose of this study was to determine the clinical and radiological results of high offset Tri-Lock BPS in unilateral primary total hip arthroplasty (THA) at a minimum follow-up of 3 years. METHODS: 55 patients who underwent cementless THA with high offset Tri-lock BPS from 2017 to 2018 were followed for a minimum follow-up of 3 years. Patients were assessed clinically for complications, Harris hip score (HHS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Oxford Hip Score (OHS). Femoral offset (FO), acetabular offset (AO), hip offset (HO), HO difference, and leg length discrepancy (LLD) were measured on the anteroposterior (AP) pelvic radiograph. Standard pelvic AP and lateral radiographs were used to evaluate for evidence of bone ingrowth, stem subsidence, stem alignment, radiolucent line around the stem, osteolysis, loosening, ectopic ossification, and femoral stress shielding. RESULTS: No patients reported complications during hospitalization nor the follow-up period. At a mean follow-up of 42.5 months, the mean HHS, WOMAC, and OHS scores showed a significant improvement from preoperative to the latest follow-up. No patients reported thigh pain. No revision nor sign of radiographic loosening had been detected. The high offset Tri-Lock BPS significantly improved the FO and HO postoperatively. HO difference and LLD were balanced postoperatively. No sign of stem subsidence, radiolucent line, osteolysis, loosening, ectopic ossification, nor severe stress shielding (more than grade 3-4) were observed at the latest follow-up. CONCLUSION: The high offset Tri-Lock BPS demonstrated excellent clinical and radiographic outcomes at a minimum follow-up of 3 years. HO difference and LLD between legs decreased significantly and achieved balance postoperatively. Long-term follow-up is required for a definitive conclusion.

10.
J Orthop Surg Res ; 16(1): 643, 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34717693

RESUMO

BACKGROUND: Enhanced recovery after surgery (ERAS) program advocates implementation of perioperative goal-directed fluid therapy and reduced application of colloidal fluids. It should be used reasonably selectively in high-risk patients despite the clear efficacy of human albumin (HA). Therefore, it is vital to identify the risk factors for the use of HA. This study aims to determine the incidence and risk factors of HA administration in patients undergoing total hip or knee arthroplasty (THA, TKA). METHODS: We identified patients undergoing THA or TKA in multiple institutions from 2014 to 2016 and collected patient demographics and perioperative variables. The criterion of HA administration was defined as a postoperative albumin level < 32 g/L or 32 to 35 g/L for at-risk patients. We compared 14 variables between patients who received HA administration and those who did not after stratification by the preoperative albumin (pre-ALB) level. Multivariable regressions identified the independent risk factors associated with HA administration. RESULTS: In total, 958 (20.3%) of 4713 patients undergoing THA and 410 (9.7%) of 4248 patients undergoing TKA received HA administration. In addition to pre-ALB < 35 g/L, preoperative anemia (odds ratio [OR] 2.12, P = 0.001; OR 1.39, P < 0.001) and drain use (OR 3.33, P = 0.001; OR 4.25, P < 0.001) were also independent risk factors for HA administration after THA regardless pre-ALB < 35 g/L or not, and patients undergoing TKA diagnosed of rheumatoid arthritis or ankylosing spondylitis tended to receive HA administration regardless pre-ALB < 35 g/L or not (OR 3.67, P = 0.002; OR 2.06, P < 0.001). CONCLUSIONS: The incidence of HA administration was high in patients undergoing THA or TKA, and several variables were risk factors for HA administration. This finding may aid surgeons in preoperatively identifying patients requiring HA administration and optimizing perioperative managements.

11.
Front Med (Lausanne) ; 8: 737360, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34568392

RESUMO

Background: Whole-body plethysmography (WBP) is the gold standard for measuring lung volume, but its clinical application is limited as it requires expensive equipment and is not simple to use. Studies have shown that the single-breath helium dilution (SBHD) method, which is commonly used in clinical practice, significantly underestimates lung volume in patients with obstructive lung disease (OLD). By comparing the differences in lung volume measured using SBHD and WBP, we aimed to establish a correction equation for the SBHD method to determine the total lung volume in patients with OLD of different severities. Methods: From 628 patients with OLD simultaneously subjected to SBHD and WBP, 407 patients enrolled between January 2018 and November 2019 were in the training group and 221 enrolled between December 2019 and December 2020 were in the prospective verification cohort. The multiple linear regression equation was used for data in the training group to establish a correction equation for SBHD to determine the total lung volume, and this was validated in the prospective validation cohort. Results: There was a moderate positive correlation between total lung capacity (TLC) determined using the SBHD [TLC (SBHD)] and WBP methods [TLC (WBP)] (r = 0.701; P < 0.05), and the differences between TLC (SBHD) and TLC (WBP) (ΔTLC) were related to the severity of obstruction. As the severity of obstruction increased, the TLC was underestimated by the SBHD method. We established the following correction equation: TLC (adjusted SBHD) (L) = -0.669 + 0.756*TLC(SBHD)(L) - 0.047* F E V 1 F V C +0.039*height (cm)-0.009*weight(kg)(r2 = 0.753 and adjusted r2 = 0.751). Next, we validated this equation in the validation cohort. With the correction equation, no statistical difference was observed between TLC (adjusted SBHD) and TLC (WBP) among the obstruction degree groups (P > 0.05). Conclusions: The SBHD method is correlated with WBP to measure the total lung volume, but the SBHD method presents limitations in determining the total lung volume in patients with obstructive lung disease. Here, we established an effective and reliable correction equation in order to accurately assess the total lung volume of patients with OLD using the SBHD method.

12.
BMC Musculoskelet Disord ; 22(1): 834, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34587938

RESUMO

BACKGROUND: Current evidence does not recommend screening urine culture and curing asymptomatic bacteriuria (ASB) before joint arthroplasty. The bacteriuria count on pre-operative urinalysis is a more common clinical parameter. We aimed to investigate whether the bacteriuria count on preoperative urinalysis can increase postoperative wound complications in primary total hip arthroplasty (THA). METHODS: We conducted a retrospective study that included patients who underwent primary THA in our institution from 2012 to 2018. We obtained preoperative urinalysis results before THA during the same hospitalization and identified patients with abnormal urinalysis. Receiver operating characteristic (ROC) curves were first generated to evaluate the predicted value of leukocyte esterase (LE), nitrite, bacteriuria, and pyuria in the urinalysis for superficial wound infection. Then, all included patients were divided into two groups according to the preoperative urinalysis: a bacteriuria-positive group and a bacteriuria-negative group. The primary outcome was the superficial wound infection rate within 3 months postoperatively, and the secondary outcomes included wound leakage, prosthetic joint infection (PJI), pulmonary infection, urinary tract infection (UTI), readmission rate within 3 months postoperatively, and length of stay (LOS) during hospitalization. We utilized univariable analyses to compare the outcomes between the two groups. A multivariable logistic regression model was generated to explore the potential association between bacteriuria and the risk of superficial wound infection, wound leakage, and readmission rate controlling for baseline values. RESULTS: A total of 963 patients were included in the study. One hundred sixty patients had abnormal urinalysis. The AUCs for LE, nitrite, bacteriuria, and pyuria were 0.507 (95% confidence interval (CI), 0.315 to 0.698), 0.551 (0.347 to 0.756), 0.675 (0.467 to 0.882), and 0.529 (0.331 to 0.728), respectively. Bacteriuria was diagnostically superior to LE, nitrite, and pyuria. Among the 963 patients, 95 had a positive bacteriuria on preoperative urinalysis, and only 9 (9.5%) had a positive urine culture. Compared with the bacteriuria-negative group, the bacteriuria-positive group had a higher superficial wound infection rate (4.2% vs. 0.6%, P = 0.008), higher wound leakage rate (11.6% vs. 4.5%, P = 0.007), higher readmission rate (5.3% vs. 1.3%, P = 0.015) within 3 months postoperatively and longer LOS (6.19 ± 2.89 days vs. 5.58 ± 2.14 days, P = 0.011). After adjustment, the bacteriuria-positive group had a significantly increased risk of superficial wound infection (OR = 7.587, 95%CI: 2.002 to 28.755, P = 0.003), wound leakage (OR = 3.044, 95%CI: 1.461 to 6.342, P = 0.003), and readmission (OR = 4.410, 95%CI: 1.485 to 13.097, P = 0.008). CONCLUSION: Preoperative bacteriuria positivity on urinalysis significantly increased the risk of postoperative wound complications, readmission, and LOS in primary THA regardless of the result of the urine culture. Urinalysis is a fast and cost-acceptable test whose advantages have been underestimated. LEVEL OF EVIDENCE: Level III, observational study.


Assuntos
Artroplastia de Quadril , Bacteriúria , Infecções Urinárias , Artroplastia de Quadril/efeitos adversos , Bacteriúria/diagnóstico , Bacteriúria/epidemiologia , Humanos , Estudos Retrospectivos , Urinálise
13.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 35(9): 1125-1132, 2021 Sep 15.
Artigo em Chinês | MEDLINE | ID: mdl-34523277

RESUMO

Objective: To compare the effectiveness of unicompartmental knee arthroplasty (UKA) and total knee arthroplasty (TKA) in the treatment of severe medial compartment osteoarthritis (OA). Methods: A clinical data of 69 patients (69 knees), who underwent joint replacement due to severe medial compartment OA between February 2015 and September 2018 and met the selection criteria, was retrospectively analyzed. Among them, 38 cases were treated with UKA (UKA group) and 31 cases with TKA (TKA group). There was no significant difference in gender, age, body mass index, course of disease, lesion side, and preoperative visual analogue scale (VAS) score, Hospital for Special Surgery (HSS) score, Western Ontario and McMaster University Osteoarthritis Index (WOMAC) score, Feller score, range of motion of knee, physiological and psychological scores of short-form 12 health survey scale (SF-12) between the two groups ( P>0.05). The femorotibial angle (FTA) of TKA group was bigger than that of UKA group, and hip-knee-ankle angle (HKA) was smaller, showing significant differences ( P<0.05). The operative time, incision length, blood loss, time for flexion 90°, ambulation time, hospital stay, and incidence of deep venous thrombosis of lower extremity were recorded and compared between the two groups. The VAS score, HSS score, WOMAC score, Feller score, range of motion, and physiological and psychological scores of SF-12 were used to evaluate patients' quality of life. FTA, HKA, and prosthesis looseness were observed by X-ray films. Kaplan-Merier survival analysis was used to evaluate the survival rate of prosthesis. Results: All operations were successfully completed in both groups. Compared with TKA group, UKA group had shorter incision length, longer operative time, and less blood loss ( P<0.05). There was no significant difference in time for flexion 90°, ambulation time, hospital stay, and the incidence of deep venous thrombosis of lower extremity between the two groups ( P>0.05). The incisions in both groups healed by first intention. During follow-up, 3 patients in the UKA group and 1 patient in the TKA group developed mild anterior knee pain. Patients were followed up (30.7±9.6) months in the UKA group and (34.9±8.7) months in the TKA group, and the difference was not significant ( t=-1.832, P=0.071). At last follow-up, there were significant differences in the HSS score, Feller score, WOMAC score, range of motion, VAS score, and physiological and psychological scores of SF-12 between pre- and post-operation ( P<0.05). The range of motion in the UKA group was bigger than that in the TKA group ( Z=-2.666, P=0.008), and there was no significant difference in the other indexes between the two groups ( P>0.05). X-ray films showed that the alignment of the two groups recovered well, and the FTA and HKA of the two groups were improved at 1 week after operation ( P<0.05). No radiolucency was found around the prosthesis during follow-up, no prosthesis loosening and meniscal bearing dislocation occurred. The survival rates of the prostheses in the two groups were 100%. Conclusion: For severe medial compartment OA, the early survival rates of the two prostheses are similar, but UKA has less traumatic, can preserve the normal structure of the knee, and the range of motion of the knee after operation is significantly better than TKA.


Assuntos
Artroplastia do Joelho , Prótese do Joelho , Osteoartrite do Joelho , Humanos , Articulação do Joelho/cirurgia , Osteoartrite do Joelho/cirurgia , Qualidade de Vida , Amplitude de Movimento Articular , Estudos Retrospectivos , Resultado do Tratamento
16.
Clin Cancer Res ; 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34475101

RESUMO

PURPOSE: Pyruvate kinase M2 (PKM2) catalyzes the final step in glycolysis, a key process of cancer metabolism. PKM2 is preferentially expressed by glioblastoma (GBM) cells with minimal expression in healthy brain. We describe the development, validation, and translation of a novel PET tracer to study PKM2 in GBM. We evaluated 1-((2-fluoro-6-[18F]fluorophenyl)sulfonyl)-4-((4-methoxyphenyl)sulfonyl)piperazine ([18F]DASA-23) in cell culture, mouse models of GBM, healthy human volunteers, and patients with GBM. EXPERIMENTAL DESIGN: [18F]DASA-23 was synthesized with a molar activity of 100.47 ± 29.58 GBq/µmol and radiochemical purity >95%. We performed initial testing of [18F]DASA-23 in GBM cell culture and human GBM xenografts implanted orthotopically into mice. Next, we produced [18F]DASA-23 under FDA oversight, and evaluated it in healthy volunteers and a pilot cohort of patients with glioma. RESULTS: In mouse imaging studies, [18F]DASA-23 clearly delineated the U87 GBM from surrounding healthy brain tissue and had a tumor-to-brain ratio of 3.6 ± 0.5. In human volunteers, [18F]DASA-23 crossed the intact blood-brain barrier and was rapidly cleared. In patients with GBM, [18F]DASA-23 successfully outlined tumors visible on contrast-enhanced MRI. The uptake of [18F]DASA-23 was markedly elevated in GBMs compared with normal brain, and it identified a metabolic nonresponder within 1 week of treatment initiation. CONCLUSIONS: We developed and translated [18F]DASA-23 as a new tracer that demonstrated the visualization of aberrantly expressed PKM2 for the first time in human subjects. These results warrant further clinical evaluation of [18F]DASA-23 to assess its utility for imaging therapy-induced normalization of aberrant cancer metabolism.

17.
Clin Rheumatol ; 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34490511

RESUMO

BACKGROUND: Previous cross-sectional studies have demonstrated the high prevalence of depression and comorbidity in knee osteoarthritis (KOA), and KOA or its impact on lifestyle was seen as a potential trigger factor of depression and comorbidity. However, the exact onset and progression pattern of depression and comorbidity in KOA was still unknown. METHODS: Group-based trajectory modeling (GBTM) analysis was conducted in the 2833 subjects selected from the osteoarthritis initiative (OAI) database. Eight-year trajectories were determined and described. Baseline characteristics were investigated in multi-variable regression to detect the risk factors of the unfavored trajectory. RESULTS: Stable trajectory (70.4%) and worsening trajectory (29.6%) were identified in comorbidity. The risk factors for the worsening trajectory membership were the obesity (OR = 1.47 CI = [1.20, 1.79], P < 0.001), older age (OR = 1.74, CI = [1.41, 2.16], P < 0.001), and smoke (OR = 1.30, CI = [1.08, 1.57], P < 0.01) at baseline. Stable trajectory (52.0%), slow-worsening trajectory (40.5%), and fast-worsening trajectory (7.5%) were identified in depression symptoms. The risk factors for the fast-worsening trajectory membership were female (OR = 1.51 CI = [1.03, 2.20], P < 0.05), lower income (OR = 1.52, CI = [1.01, 2.27], P < 0.05), and smoke (OR = 1.30, CI = [1.08, 1.57], P < 0.01) at baseline. CONCLUSION: A significant amount of KOA subjects tends to develop depression symptoms and comorbidity. Managing related risk factors, like weight loss or smoking cessation, might have considerable significance in preventing or delaying depression symptoms and comorbidity in KOA. Key Points • The first study investigating the trajectory of comorbidity progression in KOA. • Approximately 7.5% of KOA patients tend to develop depression symptoms quite rapidly, and 30% of KOA patients tend to develop comorbidity • Risk factors of worsening trajectories were identified: obesity, older age, smoking, female, and lower income.

18.
J Cancer ; 12(19): 5807-5816, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34475994

RESUMO

Background: Laryngeal squamous cell carcinoma (LSCC) is one of the most common malignancy in the respiratory tract and could reduce the quality of life seriously like dyspnea, dysphonia and dysphagia. Moreover, 5-year survival rate has decreased over the past 40 years. This study was designed to identify mRNAs that related to prognosis in LSCC to enable early detection and outcome improvement. Methods: Gene expression profiles from Gene Expression Omnibus (GEO) (GSE59102, GSE84957) and The Cancer Genome Atlas (TCGA) were analyzed to identify differentially expressed genes (DEGs) with the help of bioinformatics tools. Functional enrichment analyses including Gene Ontology (GO) and pathway analysis were carried out to investigate the role of those genes and underlying molecular mechanisms in LSCC. Cox's regression analyses (univariate, LASSO and multivariate in order) were utilized to identify DEGs related with patients' overall survival and a 4-mRNA-based prognostic risk score model was established. Univariate and multivariate Cox's regression analyses were then performed on LSCC data (90 patients left) to identify independent predictors of OS, including the signature and clinicopathologic variables. The prognostic value of the gene signature was further validated and the genes were analyzed by GEPIA to get pan-cancer expression profiles. Results: 444 differentially expressed mRNAs (250 up-regulated, 194 down-regulated) were identified based on the threshold of fold change > 2 and adjusted p value < 0.05. Univariate Cox's regression analysis showed that high risk score (HR: 3.056, 95% confidence interval [CI]: 0.135-0.649, p<0.001) and female (HR: 0.296, 95% CI: 2.020-4.624, p=0.002) were associated with relatively poor prognosis. Further multivariate Cox's regression analysis indicated that risk score and gender were independent prognostic factors (p<0.05). The risk score model could stratify patients into high- and low­risk groups, which presents significantly differential overall survival (p= 8.252e-04). The AUCs of 1-, 3- and 5-year OS were 0.724, 0.783 and 0.818, respectively. Conclusions: Our study provides evidence that the four-mRNA signature could serve as a biomarker to predict prognosis in LSCC, especially in long-term.

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