Expression of Glucose Metabolism-Related Proteins in Adrenal Neoplasms

Pathobiology ◽  
2021 ◽  
pp. 1-10
Author(s):  
Eun Kyung Kim ◽  
Hye Min Kim ◽  
Ja Seung Koo

<b><i>Purpose:</i></b> The aim of this study was to investigate the expression patterns of glucose metabolism-related proteins and their clinicopathologic implications in adrenal cortical neoplasms (ACN) and pheochromocytoma (PCC). <b><i>Methods:</i></b> Immunohistochemical staining was performed to evaluate glucose metabolism-related proteins (GLUT1, CAIX, hexokinase II, G6PDH, PHGDH, and SHMT1) in 132 ACN cases (115 adrenal cortical adenoma [ACA] and 17 adrenal cortical carcinoma [ACC]) and 189 PCC cases. <b><i>Results:</i></b> Expression levels of GLUT1 in tumor cells ([T]; <i>p</i> &#x3c; 0.001), GLUT1 in stromal cells ([S]; <i>p</i> &#x3c; 0.001), G6PDH (<i>p</i> &#x3c; 0.001), and SHMT1 (<i>p</i> = 0.002) were higher in ACN than in PCC. GLUT1 (T; <i>p</i> = 0.045) and PHGDH (<i>p</i> = 0.043) levels were higher in ACC than in ACA. In a univariate analysis of ACN, GLUT1 (T; <i>p</i> = 0.017), CAIX (S; <i>p</i> = 0.003), and PHGDH (<i>p</i> = 0.009) levels were correlated with a shorter overall survival (OS). GLUT1 (T; <i>p</i> = 0.001) and PHGDH (<i>p</i> &#x3c; 0.001) were related to a shorter OS in PCC. GLUT1 (T) positivity (<i>p</i> = 0.043) in ACN predicted a poor OS in a multivariate Cox analysis. In PCC, high GAPP score (<i>p</i> = 0.026), GLUT1 (T; <i>p</i> = 0.002), and PHGDH (<i>p</i> &#x3c; 0.001) were independent prognostic factors for poor OS. <b><i>Conclusions:</i></b> The adrenal gland tumors ACN and PCC had different expression patterns of glucose metabolism-related proteins (GLUT1, G6PDH, and SHMT1), with higher expression levels in ACN than in PCC. GLUT1 and PHGDH were significant prognostic factors in these adrenal neoplasms.

2017 ◽  
Vol 2017 ◽  
pp. 1-10
Author(s):  
Hye Min Kim ◽  
Ja Seung Koo

Purpose. Although currently classified as variants of follicular neoplasms (FNs), Hürthle cell neoplasms (HCNs) exhibit distinct biological characteristics. Hence, the metabolism of both neoplasms may also be different. The aims of this study were to investigate and compare the expression of glycolysis-related proteins in HCNs and FNs and to determine the clinical implications of such expression. Methods. Tissue microarrays were constructed with 265 samples of FNs (112 follicular carcinomas (FCs) and 153 follicular adenomas (FAs)) as well as 108 samples of HCNs (27 Hürthle cell carcinomas (HCCs) and 81 Hürthle cell adenomas (HCAs)). Immunohistochemical staining for the glycolysis-related molecules Glut-1, hexokinase II, CAIX, and MCT4 was performed. Results. The expression levels of Glut-1, hexokinase II, CAIX, and MCT4 were significantly higher in HCNs than in FNs (p<0.001). Glut-1, hexokinase II, CAIX, and MCT4 expression levels were highest in HCC, followed by HCA, FC, and FA (all p<0.001). In HCC, hexokinase II positivity was associated with large tumor size (>4 cm) (p=0.046), CAIX positivity with vascular invasion (p=0.005), and MCT4 positivity with extrathyroidal extension (p=0.030). Conclusion. The expression levels of the glycolysis-related proteins Glut-1, hexokinase II, CAIX, and MCT4 were higher in HCNs than in FNs and in HCCs than in HCAs.


2021 ◽  
Vol 22 (19) ◽  
pp. 10490
Author(s):  
Hye Min Kim ◽  
Ja Seung Koo

The aim of this research was to evaluate the expression and concomitant implications of LC3A, LC3B, beclin-1, and p62, which are key components of autophagy in human adrenal gland tumors. Tissue microarray was made for 321 cases of adrenal gland tumor (adrenal cortical adenoma (ACA): 115, adrenal cortical carcinoma (ACC): 17, and pheochromocytoma (PCC): 189). Immunohistochemical staining was performed for beclin-1, p62, LC3A, and LC3B, and the results were compared with the patients’ clinicopathologic parameters. LC3A, LC3B, beclin-1, and LC3B isolated single positive cells (ISPC) positivity rates were higher in PCC than in adrenal cortical tumor (ACT), whereas p62 positivity was lower in PCC than in ACT. The proportion of positive LC3B (ISPC) was higher in ACC than in ACA. In addition, the proportion of cells positive for p62 and LC3B (ISPC) was significantly higher in PCCs with a GAPP score of ≥3. In univariate Cox analysis, p62 positivity (p = 0.014) and the presence of p62 (ISPC) (p = 0.001) were associated with shorter disease-free survival in PCC. Moreover, p62 positivity was predictive of shorter overall survival (OS) in patients with PCC by multivariate analysis (relative risk, 6.240; 95% CI, 1.434–27.15; p = 0.015). Differences were found in the expression of autophagy-related proteins according to adrenal gland tumor types. Compared to ACT, the proportion of LC3A, LC3B, beclin-1, and LC3B (ISPC) positivity was higher in PCC, whereas p62 positivity was lower. Similarly, p62 positivity in PCC was associated with patient prognosis of OS.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2763-2763
Author(s):  
Stefano Sacchi ◽  
Samantha Pozzi ◽  
Raffaella Marcheselli ◽  
Stefano Luminari ◽  
Massimo Federico ◽  
...  

Abstract Fifty-four Pts entered this trial between January 2000 and December 2002. Eligible Pts had histologic documentation of CD 20+ relapsed FL, according to the revised European/American Lymphoma classification, that required treatment, measurable lesion, and an ECOG performance status of 0 or 1. Pts were further required to be aged 18–70 years, and to have undergone < 3 previous lines of chemotherapy. Pts received FC + R chemoimmunotherapy consisting of F 25 mg/m2 and C 300 mg/m2/day for 3 consecutive days every 3 weeks for 4 cycles. R 375 mg/m2 I.V. infusion was administered starting 2 weeks following the first FC course and then on day 1 of each cycle thereafter. Clinical response were defined according to the International Working Group recommendations. BCL 2 analysis was performed by PCR assay. DR, TTP and OS were analyzed by Kaplan-Meier method. Cox analysis was used to analyse the association of baseline prognostic factors with response to treatment, DR,TTP and OS. The overall response rate for all 54 Pts by ITT analysis was 90%; forty Pts (74%), obtained complete responses. Progression occurred in 3 Pts ( 6% ) and 2 Pts dropped out of the trial: 1 for toxicity and 1 refused to start with therapy. A univariate analysis of baseline prognostic factors demonstrated that none of these factors predicted for response to treatment. There were 29 Pts out of 45 tested, positive for BCL 2 before therapy. Among these, 22 Pts were evaluated after treatment and 19 ( 86%) converted to BCL negativity. At last follow up (FU), 40 Pts were alive, 31 with ongoing response and 9 with progressive disease. The median DR, TTP and OS have not been reached after a median FU time of 45 months ( range, 1 to 74 months ). The median DR in the 49 Pts who have reached CR or PR was 35 months ( range, 6 to 70 months). None of the baseline prognostic characteristics was significantly related to DR. The median TTP in all 54 Pts, was 36 months ( range, 1 to 74 months ).BCL2 positivity and < 2 previous treatments were related with better TTP (p<0.05 ) OS rate at 4 years was 75%. Toxicity was evaluable in 52 Pts. The most common severe side effects were hematologic, and included 21 cases of neutropenia, 3 cases of thrombocytopenia and 2 cases of anemia. Infectious complications manifested in 3 Pts and 1 died for pneumonitis. Treatment delays of 1–3 weeks was necessary in 12 patients. The results of our trial have demonstrated that FC+R chemoimmunotherapy is active and relatively well tolerated. The OR rate of 90%, associated with an excellent molecular remission rate, and the mean DR of 35 months compares favourably with the results obtained in other trials in similar subset of patients and supports the use of an FC+R arm in future controlled trials.


2000 ◽  
Vol 18 (5) ◽  
pp. 1027-1027 ◽  
Author(s):  
M.A. Grotzer ◽  
A.J. Janss ◽  
K.-M. Fung ◽  
J.A. Biegel ◽  
L.N. Sutton ◽  
...  

PURPOSE: To identify biologic prognostic factors in childhood primitive neuroectodermal tumors (PNET), including medulloblastoma, that accurately define patient groups with sufficiently good prognosis to permit a reduction in treatment intensity. PATIENTS AND METHODS: We determined expression levels of the neurotrophin receptor TrkC mRNA in formalin-fixed tumor samples from 87 well characterized PNET patients using in situ hybridization. Comparison of TrkC mRNA expression levels with clinical and other laboratory variables was performed using univariate and multivariate Cox regression analysis. RESULTS: High TrkC mRNA expression was found to be associated more with higher 5-year cumulative survival rate than was low TrkC mRNA expression (89% v 46%, respectively). When compared with established clinical prognostic factors and laboratory variables of potential prognostic significance, TrkC mRNA expression, by univariate analysis, was found to be the single most powerful predictor of outcome (hazards ratio, 4.81; P < .00005), exceeding all clinical prognostic factors. In multivariate analysis, the hazards ratio remained significant (P < .00005). CONCLUSION: High TrkC mRNA expression in PNET is a powerful independent predictor of favorable clinical outcome. Assessment of TrkC mRNA levels may aid in treatment planning for patients with PNETs and should be incorporated prospectively into PNET clinical trials.


2016 ◽  
Vol 1 (1) ◽  
Author(s):  
Manraj S. Kang ◽  
Kamal Sahni ◽  
Piyush Kumar ◽  
Rajneesh Madhok ◽  
Ratna Saxena ◽  
...  

<bold>Introduction:</bold> Cervical cancer is most common cancer in the rural and second most common in urban areas of our country. It accounts for 16% of all cancers. There are various clinical, Paper Submission Datepathological and radiological factors which dictate the prognosis of these cancer cervix patients. The present study evaluates clinical, pathological and radiological prognostic factors in cancer cervix treated with concurrent chemoradiation. <bold>Material and Methods:</bold> A total of 32 patients seen between 2012 and 2014 patients planned concurrent chemoradiation were evaluated in terms of clinical (age, stage, Hb% and HPV Paper Publication Date infection), pathological (histopathology type and subtype, grade, mitotic index, lymph-July 2016 vascular invasion and necrosis) and radiological (parametrial extension, disease dimension, lymph node, hydronephrosis and vascularity of tumour) prognostic factors. After pre-DOI treatment evaluation patient was planned for 3 Dimentional-Conformal Radiotherapy (50Gy/25#/5 weeks) with concurrent chemotherapy (Cisplatin 35mg/m<sup>2</sup>) followed by 3 applications of Intracavitary radiotherapy (6Gy/fraction) with 6 months follow up. Response was accessed according to WHO response criteria and univariate analysis was done using chi-square test. <bold>Results:</bold> Clinical factors: Age – better disease free survival in older patients (p value=0.003), stage - Lower stage had better survival (for stage Ib-IIa vs stage IIb p value = 0.003 and for stage Ib vs. IIIb p value = 0.0005), Hb% - 57% patients with Hb <10g/dl had recurrence at end of 6 months (p value=0.00001), HPV – High recurrence with HPV presence. Pathological factors like high Mitotic Index had more residual disease (p=0.0009), grade - No statistical significance. Radiological factors- volume of disease - 35 % patients with volume of disease > 6 cm had disease at end of 6 months, hydronephrosis - 40 % patient with hydronephrosis had recurrence (p value = 0.0005) at end of 6 months follow up and vascularity of tumour showed statistically no difference. <bold>Conclusion:</bold> Hb <10%, HPV infection, Mitotic index (3-5/HPF), stage IIIB, pelvic nodes were concluded as the independent poor prognostic factors.


Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 712
Author(s):  
Joohee Lee ◽  
Young Seok Cho ◽  
Jhingook Kim ◽  
Young Mog Shim ◽  
Kyung-Han Lee ◽  
...  

Background: Imaging tumor FDG avidity could complement prognostic implication in thymic epithelial tumors. We thus investigated the prognostic value of volume-based 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT parameters in thymic epithelial tumors with other clinical prognostic factors. Methods: This is a retrospective study that included 83 patients who were diagnosed with thymic epithelial tumors and underwent pretreatment 18F-FDG PET/CT. PET parameters, including maximum and average standardized uptake values (SUVmax, SUVavg), metabolic tumor volume (MTV), and total lesion glycolysis (TLG), were measured with a threshold of SUV 2.5. Univariate and multivariate analysis of PET parameters and clinicopathologic variables for time-to-progression was performed by using a Cox proportional hazard regression model. Results: There were 21 low-risk thymomas (25.3%), 27 high-risk thymomas (32.5%), and 35 thymic carcinomas (42.2%). Recurrence or disease progression occurred in 24 patients (28.9%). On univariate analysis, Masaoka stage (p < 0.001); histologic types (p = 0.009); treatment modality (p = 0.001); and SUVmax, SUVavg, MTV, and TLG (all p < 0.001) were significant prognostic factors. SUVavg (p < 0.001) and Masaoka stage (p = 0.001) were independent prognostic factors on multivariate analysis. Conclusion: SUVavg and Masaoka stage are independent prognostic factors in thymic epithelial tumors.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Ruifeng Cui ◽  
Xiaoge Wang ◽  
Waqar Afzal Malik ◽  
Xuke Lu ◽  
Xiugui Chen ◽  
...  

Abstract Background The Raffinose synthetase (RAFS) genes superfamily is critical for the synthesis of raffinose, which accumulates in plant leaves under abiotic stress. However, it remains unclear whether RAFS contributes to resistance to abiotic stress in plants, specifically in the Gossypium species. Results In this study, we identified 74 RAFS genes from G. hirsutum, G. barbadense, G. arboreum and G. raimondii by using a series of bioinformatic methods. Phylogenetic analysis showed that the RAFS gene family in the four Gossypium species could be divided into four major clades; the relatively uniform distribution of the gene number in each species ranged from 12 to 25 based on species ploidy, most likely resulting from an ancient whole-genome polyploidization. Gene motif analysis showed that the RAFS gene structure was relatively conservative. Promoter analysis for cis-regulatory elements showed that some RAFS genes might be regulated by gibberellins and abscisic acid, which might influence their expression levels. Moreover, we further examined the functions of RAFS under cold, heat, salt and drought stress conditions, based on the expression profile and co-expression network of RAFS genes in Gossypium species. Transcriptome analysis suggested that RAFS genes in clade III are highly expressed in organs such as seed, root, cotyledon, ovule and fiber, and under abiotic stress in particular, indicating the involvement of genes belonging to clade III in resistance to abiotic stress. Gene co-expressed network analysis showed that GhRFS2A-GhRFS6A, GhRFS6D, GhRFS7D and GhRFS8A-GhRFS11A were key genes, with high expression levels under salt, drought, cold and heat stress. Conclusion The findings may provide insights into the evolutionary relationships and expression patterns of RAFS genes in Gossypium species and a theoretical basis for the identification of stress resistance materials in cotton.


2021 ◽  
Vol 108 (Supplement_3) ◽  
Author(s):  
G Martínez Izquierdo ◽  
A R Arnaiz Pérez ◽  
E Escolano Fernández ◽  
M Merayo Álvarez ◽  
B Carrasco Aguilera ◽  
...  

Abstract INTRODUCTION Renal cell carcinoma (RCC) represents 3% of overall malignant neoplasms in adults. However, its aetiology has not been clearly established. Although surgery represents the cornerstone in treatment, recurrence postoperative rates are around 20-30%, what implies prognostic factors search must be mandatory in order to help to plan de follow-up and the different adjuvant therapy possibilities available in case they were necessary. MATERIAL AND METHODS A retrospective observational study was carried out in 110 patients who underwent radical nephrectomy between 2004 and 2018, with the aim of identifying possible prognostic factors of recurrence of RCC after these surgeries. Preoperative data (epidemiological, comorbidities and laboratory tests), surgical, pathological and variables related to follow-up were taken into account. A univariate and multivariate analysis were performed, using chi-square test and logistic regression, respectively. RESULTS The median follow-up time was 53.5 months (SD = 35.8), time in which 19 patients had a recurrence of RCC after radical nephrectomy (17.2%). Histopathological items such as the surgical piece size, the nodal and microvascular invasion, the renal sinus invasion and the presence of necrosis in the surgical piece were associated with RCC recurrence in the univariate analysis, while only the presence of necrosis in the surgical piece showed a significant result in the multivariate analysis (p = 0.004). CONCLUSIONS Histopathological analysis, highlighting the presence of necrosis in the histological sample, was proved to be the main risk factor of RCC recurrence.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Li Zhang ◽  
Hao Niu ◽  
Ping Yang ◽  
Jie Ma ◽  
Bao-Ying Yuan ◽  
...  

Abstract Background Early screening and intervention therapies are crucial to improve the prognosis of hepatocellular carcinoma (HCC) patients with bone metastasis. We aimed to identify serum lncRNA as a prediction biomarker in HCC bone metastasis. Methods The expression levels of lnc34a in serum samples from 157 HCC patients were detected by quantitative real-time polymerase chain reaction (PCR). Univariate analysis and multivariate analysis were performed to determine statistically significant variables. Results Expression levels of lnc34a in serum from HCC patients with bone metastasis were significantly higher than those without bone metastasis. The high expressions of lnc34a, vascular invasion and Barcelona Clinic Liver Cancer (BCLC) stage were associated with bone metastasis by analysis. Moreover, lnc34a expression was specifically associated with bone metastasis rather than lung or lymph node metastasis in HCC. Conclusions High serum lnc34a expression was a independent risk factor for developing bone metastasis in HCC.


2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Peirong Li ◽  
Tongbing Su ◽  
Deshuang Zhang ◽  
Weihong Wang ◽  
Xiaoyun Xin ◽  
...  

AbstractHeterosis is a complex phenomenon in which hybrids show better phenotypic characteristics than their parents do. Chinese cabbage (Brassica rapa L. spp. pekinensis) is a popular leafy crop species, hybrids of which are widely used in commercial production; however, the molecular basis of heterosis for biomass of Chinese cabbage is poorly understood. We characterized heterosis in a Chinese cabbage F1 hybrid cultivar and its parental lines from the seedling stage to the heading stage; marked heterosis of leaf weight and biomass yield were observed. Small RNA sequencing revealed 63 and 50 differentially expressed microRNAs (DEMs) at the seedling and early-heading stages, respectively. The expression levels of the majority of miRNA clusters in the F1 hybrid were lower than the mid-parent values (MPVs). Using degradome sequencing, we identified 1,819 miRNA target genes. Gene ontology (GO) analyses demonstrated that the target genes of the MPV-DEMs and low parental expression level dominance (ELD) miRNAs were significantly enriched in leaf morphogenesis, leaf development, and leaf shaping. Transcriptome analysis revealed that the expression levels of photosynthesis and chlorophyll synthesis-related MPV-DEGs (differentially expressed genes) were significantly different in the F1 hybrid compared to the parental lines, resulting in increased photosynthesis capacity and chlorophyll content in the former. Furthermore, expression of genes known to regulate leaf development was also observed at the seedling stage. Arabidopsis plants overexpressing BrGRF4.2 and bra-miR396 presented increased and decreased leaf sizes, respectively. These results provide new insight into the regulation of target genes and miRNA expression patterns in leaf size and heterosis for biomass of B. rapa.


Sign in / Sign up

Export Citation Format

Share Document