ABSTRACT
Papillary thyroid carcinoma (PTC) is a common endocrine cancer with a good prognosis. Radioactive iodine is thought to be useful for individuals who have had a total or almost total thyroidectomy, but its effects are still controversial. The effects of radioactive iodine-131 (I-131) treatment on oxidative and chromosomal damage in PTC patients were examined in this study, which was carried out with 16 patients newly diagnosed with PTC and 20 healthy control subjects with similar age and gender. Blood samples were taken from patients with PTC at five sampling times (before total thyroidectomy, after total thyroidectomy, and seven days, six months, and one year after treatment) and from control subjects. The cytokinesis block micronucleus cytome (CBMN-cyt) assay parameters in peripheral blood lymphocytes of patients with PTC and controls were evaluated and plasma 8-hydroxydeoxyguanosine (8-OHdG) levels were measured. Furthermore, genome instability and oxidative DNA damage in peripheral blood lymphocytes and plasma of patients with PTC were evaluated before total thyroidectomy (n=16), after total thyroidectomy (before I-131 treatment) (n=16), seven days (n=10), six months (n=5), and one year after treatment (n=5). The numbers of CBMN-cyt assay parameters (micronucleus; MN and nucleoplasmic bridges; NPB) and 8-OHdG levels in patients with PTC were determined to be significantly higher than in those of the control subjects and these values significantly decreased after total thyroidectomy (before I-131 treatment). While the number of MN, apoptotic, and necrotic cells increased after I-131 treatment, it significantly decreased after six months and one year after treatment. The results achieved in this study suggest that I-131 treatment may pose a threat to cells and that radioactive iodine therapy should be avoided (if possible) for patients with PTC after total thyroidectomy.
Subject(s)
DNA Damage , Iodine Radioisotopes , Oxidative Stress , Thyroid Cancer, Papillary , Thyroid Neoplasms , Thyroidectomy , Humans , Iodine Radioisotopes/therapeutic use , Iodine Radioisotopes/adverse effects , Thyroid Neoplasms/blood , Thyroid Neoplasms/radiotherapy , Thyroid Neoplasms/pathology , Thyroid Neoplasms/genetics , Female , Male , Adult , Middle Aged , Thyroid Cancer, Papillary/blood , Thyroid Cancer, Papillary/radiotherapy , Oxidative Stress/drug effects , Micronucleus Tests , Carcinoma, Papillary/blood , Carcinoma, Papillary/pathology , Carcinoma, Papillary/radiotherapy , Carcinoma/radiotherapy , Carcinoma/blood , Carcinoma/genetics , Lymphocytes/radiation effects , Lymphocytes/drug effects , 8-Hydroxy-2'-Deoxyguanosine/blood , Deoxyguanosine/analogs & derivatives , Deoxyguanosine/blood , Case-Control Studies , Genomic InstabilitySubject(s)
Carcinoma, Papillary , Thyroid Cancer, Papillary , Thyroid Neoplasms , Humans , Thyroid Neoplasms/pathology , Thyroid Neoplasms/drug therapy , Thyroid Cancer, Papillary/pathology , Thyroid Cancer, Papillary/drug therapy , Carcinoma, Papillary/pathology , Carcinoma, Papillary/drug therapy , Carcinoma/pathology , Carcinoma/drug therapyABSTRACT
Approximately 70% of treatment failures in nasopharyngeal carcinoma (NPC) patients are attributed to distant metastasis, yet the underlying mechanisms remain unclear. RNA 5-methylcytosine (m5C) is an emerging regulatory modification that controls gene expression and plays a critical role in tumor progression. However, there is little information on the potential roles of RNA m5C modification in NPC metastasis. In this study, we found that the m5C reader Aly/REF export factor (ALYREF) is significantly upregulated in NPC, whereby its high expression is associated with metastasis and poor prognosis. ALYREF overexpression was found to promote tumor metastasis of NPC cells in vitro and in vivo. Mechanistically, m5C-modified NOTCH1 mRNA was identified as a target of ALYREF. Moreover, ALYREF was found to upregulate NOTCH1 expression by enhancing its RNA stability in an m5C modification-dependent manner, thereby promoting the activation of the NOTCH signaling pathway and facilitating NPC metastasis. Overall, our data reveal the crucial role of ALYREF in NPC metastasis and provide a potential therapeutic target for NPC.
Subject(s)
Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Neoplasm Metastasis , RNA Stability , RNA, Messenger , Receptor, Notch1 , Humans , Receptor, Notch1/metabolism , Receptor, Notch1/genetics , Nasopharyngeal Carcinoma/genetics , Nasopharyngeal Carcinoma/pathology , Nasopharyngeal Carcinoma/metabolism , Nasopharyngeal Neoplasms/genetics , Nasopharyngeal Neoplasms/pathology , Nasopharyngeal Neoplasms/metabolism , Cell Line, Tumor , RNA, Messenger/metabolism , RNA, Messenger/genetics , Animals , Gene Expression Regulation, Neoplastic , Mice, Nude , Male , Female , Mice , Signal Transduction , Mice, Inbred BALB C , Up-Regulation/genetics , Carcinoma/metabolism , Carcinoma/genetics , Carcinoma/pathology , Middle AgedABSTRACT
BACKGROUND: ETV6 gene rearrangement is the molecular hallmark of secretory carcinoma (SC), however; the nature, frequency, and clinical implications of atypical ETV6 signal patterns by fluorescence in situ hybridization (FISH) has not yet been systematically evaluated in salivary gland neoplasms. METHODS: The clinical, histopathologic, immunohistochemical and molecular features of seven salivary SCs, including four cases with atypical ETV6 FISH patterns, were retrospectively analyzed along with a critical appraisal of the literature on unbalanced ETV6 break-apart in SCs. RESULTS: The patients were four males and three females (31-70 years-old). Five presented with a painless neck mass and two patients with recurrent disease had a history of a previously diagnosed acinic cell carcinoma of the buccal mucosa. Histologically, there were varied combinations of microcystic, papillary, tubular, and solid patterns. All tumors were diffusely positive for S100 and/or SOX10, while 2 cases also showed luminal DOG1 staining. Rearrangement of the ETV6 locus was confirmed in 5/7 cases, of which 3 cases showed classic break-apart signals, 1 case further demonstrated duplication of the ETV6 5`end and the other loss of one copy of ETV6. Two cases harbored ETV6 deletion without rearrangement. Two of the 4 cases with atypical ETV6 FISH patterns represented recurrent tumors, one with widespread skeletal muscle involvement, bone and lymphovascular invasion. Surgical treatment resulted in gross-total resection in all 7 cases, with a median follow up of 9.5 months post-surgery for primary (n = 3) and recurrent disease (n = 1). CONCLUSION: Duplication of the distal/telomeric ETV6 probe represented the most common (26/40; 65%) variant ETV6 break-apart FISH pattern in salivary SC reported in the literature and appears indicative of an aggressive clinical course.
Subject(s)
ETS Translocation Variant 6 Protein , Proto-Oncogene Proteins c-ets , Repressor Proteins , Salivary Gland Neoplasms , Humans , Male , Salivary Gland Neoplasms/genetics , Salivary Gland Neoplasms/pathology , Proto-Oncogene Proteins c-ets/genetics , Female , Adult , Aged , Middle Aged , Repressor Proteins/genetics , In Situ Hybridization, Fluorescence , Gene Rearrangement , Carcinoma/genetics , Carcinoma/pathology , Biomarkers, Tumor/genetics , Biomarkers, Tumor/analysisSubject(s)
Herpesvirus 4, Human , Nasopharyngeal Neoplasms , Humans , Nasopharyngeal Neoplasms/virology , Nasopharyngeal Neoplasms/genetics , Herpesvirus 4, Human/genetics , Herpesvirus 4, Human/isolation & purification , Epstein-Barr Virus Infections/virology , Epstein-Barr Virus Infections/complications , Nasopharyngeal Carcinoma/virology , Nasopharyngeal Carcinoma/genetics , Carcinoma/virology , Carcinoma/geneticsABSTRACT
Compared with re-radiotherapy or open surgery, endoscopic surgery for recurrent nasopharyngeal carcinoma has a better effect, which not only improves the overall survival rate, but also reduces serious complications, improves the quality of life and saves medical costs. With the advancement of modern surgical equipment and instruments, the deepening of anatomical research in the field of skull base, the improvement of surgical techniques and the development of multidisciplinary teamwork, the safety of endoscopic surgery and the rate of complete tumor resection will also increase. The indications for surgery are further expanded, and more patients with recurrent nasopharyngeal carcinoma benefit from endoscopic minimally invasive surgery. This article reviews the efficacy of endoscopic surgery for recurrent nasopharyngeal carcinoma, and then provides insights for the selection of clinical treatment strategies for recurrent nasopharyngeal carcinoma.
Subject(s)
Carcinoma , Endoscopy , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Neoplasm Recurrence, Local , Humans , Nasopharyngeal Neoplasms/surgery , Nasopharyngeal Carcinoma/surgery , Endoscopy/methods , Neoplasm Recurrence, Local/surgery , Carcinoma/surgery , Treatment Outcome , Quality of LifeABSTRACT
BACKGROUND: As a traditional Chinese fitness technique, Baduanjin is a low- to medium-intensity aerobic exercise that has a common regulatory effect on both body and mind and is also an important means of disease prevention and treatment. However, the role of Baduanjin in improving patients' nutritional status and promoting tumor recovery remains to be confirmed. OBJECTIVE: This study aims to investigate the effectiveness of the modified Baduanjin exercise on the nutritional status of patients with nasopharyngeal carcinoma. DESIGN: This is a randomized controlled trial. SETTING(S): The participants were recruited from patients in the Radiotherapy Department of the First Affiliated Hospital of Guangxi Medical University in China. PARTICIPANTS: A total of 121 patients with nasopharyngeal carcinoma were randomly divided into the control group and the Baduanjin group. Finally, 106 patients completed the study (53 cases each in the control group and the Baduanjin group) with the intervention time from the beginning to the end of radiotherapy. METHODS: The control group received conventional care (health education and regular conventional exercise), and the Baduanjin exercise group received health education and regularly improved Baduanjin exercise, with the intervention time from the beginning to the end of the radiotherapy. Patient-generated subjective global assessment (PG-SGA) was evaluated before, during (15 times), and at the end of radiotherapy as the main evaluation index to compare nutritional status between the two groups. RESULTS: From August 2022 to December 2022, 121 patients with nasopharyngeal carcinoma were randomly divided into the control group and the Baduanjin group. During the intervention, 15 patients withdrew from the study, leading to 53 of 59 patients in the control group and 53 of 62 patients in the Baduanjin group. After the intervention, the PG-SGA score, radioactive oral mucositis, and oropharyngeal pain score were lower (P < 0.05), whereas anorexia scores, the levels of hemoglobin, albumin, prealbumin, and total protein were higher than those in the control group (P < 0.05). CONCLUSIONS: Modified Baduanjin exercise can improve the nutritional status of patients with nasopharyngeal carcinoma and deserves further clinical application. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry under the registration number ChiCTR2200064519, registered on August 27, 2022. The public research topic is the construction and intervention research based on Internet + nasopharyngeal carcinoma.
Subject(s)
Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Nutritional Status , Humans , Male , Female , Nasopharyngeal Neoplasms/radiotherapy , Nasopharyngeal Carcinoma/radiotherapy , Nasopharyngeal Carcinoma/therapy , Middle Aged , Adult , China , Exercise Therapy/methods , Exercise/physiology , Carcinoma/radiotherapy , AgedABSTRACT
NUT carcinoma (nuclear protein in testis carcinoma) is a rare and highly invasive malignant tumor, which is most common in midline organs and lungs. The characteristic genetic change of NUT carcinoma is the rearrangement of NUT middle carcinoma family member 1 (NUTM1) gene. In this article, we will review the pathogenic mechanism of its most common fusion form, bromodomaincontaining protein 4 (BRD4)-NUTM1 fusion gene, and the progress in the research and development of targeting drugs.â©.
Subject(s)
Nuclear Proteins , Humans , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , Oncogene Proteins, Fusion/genetics , Oncogene Proteins, Fusion/metabolism , Animals , Carcinoma/genetics , Carcinoma/metabolism , Carcinoma/therapy , Carcinoma/drug therapy , Transcription Factors/genetics , Transcription Factors/metabolismABSTRACT
Choroid plexus carcinomas (CPCs) are rare intraventricular lesions encountered in the pediatric population. The dreaded perioperative complication causing high mortality and morbidity in patients undergoing excision of CPC is massive intraoperative hemorrhage, which results in massive blood transfusion, and coagulopathy. Hence, the main crux of perioperative management is to tackle intraoperative hemorrhage and coagulopathy by instituting goal-directed blood transfusion guided by multimodality monitoring. This case series and literature review aims to present our institutional experience wherein the patients had a favorable outcome post-excision of CPC owing to goal-directed blood transfusion protocol guided by multimodality monitoring in the perioperative period.
Subject(s)
Blood Transfusion , Carcinoma , Choroid Plexus Neoplasms , Humans , Blood Loss, Surgical/prevention & control , Blood Transfusion/methods , Carcinoma/surgery , Choroid Plexus Neoplasms/surgery , Perioperative Care/methodsABSTRACT
Multimodal medical image fusion is a perennially prominent research topic that can obtain informative medical images and aid radiologists in diagnosing and treating disease more effectively. However, the recent state-of-the-art methods extract and fuse features by subjectively defining constraints, which easily distort the exclusive information of source images. To overcome these problems and get a better fusion method, this study proposes a 2D data fusion method that uses salient structure extraction (SSE) and a swift algorithm via normalized convolution to fuse different types of medical images. First, salient structure extraction (SSE) is used to attenuate the effect of noise and irrelevant data in the source images by preserving the significant structures. The salient structure extraction is performed to ensure that the pixels with a higher gradient magnitude impact the choices of their neighbors and further provide a way to restore the sharply altered pixels to their neighbors. In addition, a Swift algorithm is used to overcome the excessive pixel values and modify the contrast of the source images. Furthermore, the method proposes an efficient method for performing edge-preserving filtering using normalized convolution. In the end,the fused image are obtained through linear combination of the processed image and the input images based on the properties of the filters. A quantitative function composed of structural loss and region mutual data loss is designed to produce restrictions for preserving data at feature level and the structural level. Extensive experiments on CT-MRI images demonstrate that the proposed algorithm exhibits superior performance when compared to some of the state-of-the-art methods in terms of providing detailed information, edge contour, and overall contrasts.
Subject(s)
Algorithms , Neoplasms , Humans , Neoplasms/diagnostic imaging , Image Processing, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Tomography, X-Ray Computed/methods , Multimodal Imaging/methods , Signal Processing, Computer-Assisted , Carcinoma/diagnostic imagingABSTRACT
Salivary glands' neoplasms are hard to diagnose and present a complex etiology. However, several viruses have been detected in these neoplasms, such as HCMV, which can play a role in certain cancers through oncomodulation. The co-infections between HCMV with betaherpesviruses (HHV-6 and HHV-7) and polyomaviruses (JCV and BKV) has been investigated. The aim of the current study is to describe the frequency of HCMV and co-infections in patients presenting neoplastic and non-neoplastic lesions, including in the salivary gland. Multiplex quantitative polymerase chain reaction was used for betaherpesvirus and polyomavirus quantification purposes after DNA extraction. In total, 50.7% of the 67 analyzed samples were mucocele, 40.3% were adenoma pleomorphic, and 8.9% were mucoepidermoid carcinoma. Overall, 20.9% of samples presented triple-infections with HCMV/HHV-6/HHV-7, whereas 9.0% were co-infections with HCMV/HHV-6 and HCMV/HHV-7. The largest number of co-infections was detected in pleomorphic adenoma cases. All samples tested negative for polyomaviruses, such as BKV and JCV. It was possible to conclude that HCMV can be abundant in salivary gland lesions. A high viral load can be useful to help better understand the etiological role played by viruses in these lesions. A lack of JCV and BKV in the samples analyzed herein does not rule out the involvement of these viruses in one or more salivary gland lesion subtypes.
Subject(s)
Coinfection , Cytomegalovirus Infections , Cytomegalovirus , Salivary Gland Neoplasms , Salivary Glands , Humans , Coinfection/virology , Cytomegalovirus Infections/virology , Cytomegalovirus Infections/diagnosis , Cytomegalovirus/genetics , Cytomegalovirus/isolation & purification , Male , Female , Salivary Gland Neoplasms/virology , Middle Aged , Adult , Aged , Salivary Glands/virology , Salivary Glands/pathology , Adenoma/virology , Aged, 80 and over , Carcinoma/virology , DNA, Viral/genetics , DNA, Viral/analysis , Young Adult , AdolescentABSTRACT
OBJECTIVE: Laryngeal preservation and a radical cure are the treatment goals for laryngeal carcinoma, and larynx-preserving therapy is generally preferred for early-stage laryngeal carcinoma. When laryngeal carcinoma recurs locally, patients are often forced to undergo total laryngectomy, resulting in loss of vocal function. However, many patients with laryngeal carcinoma who have residual or recurrent disease after radiotherapy wish to preserve their voice. The purpose of this study was to investigate the possibility of using BNCT as a larynx-preserving treatment for residual or recurrent laryngeal carcinomas following radical irradiation. PATIENTS AND METHODS: This study included 15 patients who underwent BNCT for residual or recurrent laryngeal carcinoma after radical laryngeal carcinoma irradiation. The number of treatment sessions for all patients was one irradiation. Before BNCT, the recurrent laryngeal carcinoma stage was rT1aN0, rT2N0, rT2N1, rT3N0, rT3N1, and rT4aN0 in one, six, one, three, one, and three patients, respectively. The median maximum tumor diameter before BNCT was 15 mm (8-22 mm). All patients underwent a tracheostomy before BNCT to mitigate the risk of upper airway stenosis due to laryngeal edema after BNCT. Treatment efficacy was evaluated retrospectively using monthly laryngoscopy after BNCT and contrast-enhanced CT scans at 3 months. The safety of treatment was evaluated based on examination findings and interviews with patients. RESULTS: The median hospital stay after BNCT was 2 days (1-6). The response rate at three months after BNCT in 15 patients with locally recurrent laryngeal carcinoma was 93.3 %, and the CR rate was 73.3 %. The most frequent adverse event associated with BNCT was laryngeal edema, which occurred in nine patients the day after BNCT. The average course of laryngeal edema peaked on the second day after BNCT and almost recovered after 1 week in all patients. One patient had bilateral vocal fold movement disorders. None had dyspnea because of prophylactic tracheostomy. No grade four or higher adverse events occurred. Other grade 2 adverse events included pharyngeal mucositis, diarrhea, and sore throat. Three months after BNCT, tracheostomy tubes were removed in nine patients, retinal cannulas were placed in three patients, and voice cannulas were placed in three patients. CONCLUSIONS: BNCT for locally recurrent laryngeal carcinoma can safely deliver radical irradiation to tumor tissues, even in patients undergoing radical irradiation. BNCT has shown antitumor effects against recurrent laryngeal carcinoma. However, further long-term observations of the treatment outcomes are required.
Subject(s)
Boron Neutron Capture Therapy , Laryngeal Neoplasms , Neoplasm Recurrence, Local , Organ Sparing Treatments , Humans , Male , Laryngeal Neoplasms/radiotherapy , Middle Aged , Aged , Neoplasm Recurrence, Local/radiotherapy , Female , Retrospective Studies , Boron Neutron Capture Therapy/methods , Carcinoma, Squamous Cell/radiotherapy , Aged, 80 and over , Adult , Carcinoma/radiotherapy , Tumor Burden , Treatment Outcome , Neoplasm StagingABSTRACT
ABSTRACT: We report a case of recurrent nasopharyngeal carcinoma postnasopharyngectomy, presenting with headaches. MRI revealed abnormal signals of the clivus with enhancement, and FDG PET/CT indicated intense uptake in the nasopharynx, clivus, and left neck lymph nodes. Bone SPECT/CT showed bony erosion and uptake in bilateral skull base areas. Biopsy confirmed aspergillosis. Despite the challenges in distinguishing tumor invasion from Aspergillus infection on MRI, bone SPECT/CT, and FDG PET/CT, the short postsurgery period and extensive uptake suggested skull base osteomyelitis.
Subject(s)
Aspergillosis , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Skull Base , Humans , Nasopharyngeal Carcinoma/diagnostic imaging , Nasopharyngeal Carcinoma/pathology , Nasopharyngeal Neoplasms/diagnostic imaging , Diagnosis, Differential , Skull Base/diagnostic imaging , Skull Base/pathology , Aspergillosis/diagnostic imaging , Male , Neoplasm Recurrence, Local/diagnostic imaging , Positron Emission Tomography Computed Tomography , Middle Aged , Carcinoma/diagnostic imaging , Magnetic Resonance Imaging , RecurrenceABSTRACT
When neglected for a long time, salivary gland pleomorphic adenoma (PA) can attain a considerable size, increasing the patient's morbidity along with the risk of malignant transformation. Very few case reports are available describing PA of the parotid glands presenting as a large cervicofacial mass. We report a case of epithelial myoepithelial carcinoma -a rare subtype of carcinoma ex-PA (Ca-Ex-PA) of non-luminal differentiation, that developed over a long period in a primary PA of the parotid gland and presented as a giant cervicofacial mass.
Subject(s)
Adenoma, Pleomorphic , Parotid Neoplasms , Humans , Adenoma, Pleomorphic/pathology , Adenoma, Pleomorphic/diagnosis , Adenoma, Pleomorphic/diagnostic imaging , Adenoma, Pleomorphic/surgery , Parotid Neoplasms/pathology , Parotid Neoplasms/diagnosis , Parotid Neoplasms/diagnostic imaging , Male , Parotid Gland/pathology , Parotid Gland/diagnostic imaging , Diagnosis, Differential , Female , Middle Aged , Carcinoma/pathology , Carcinoma/diagnosis , Salivary Gland NeoplasmsABSTRACT
BACKGROUND: The study aimed to evaluate the diagnostic efficacy of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) parameters in distinguishing sinonasal lymphoma from sinonasal carcinoma. METHODS: Forty-two participants with histologically confirmed sinonasal lymphomas and fifty-two cases of sinonasal carcinoma underwent imaging with a 3.0T MRI scanner. DCE-MRI and DWI were conducted, and various parameters including type of time-intensity curve(TIC), time to peak, peak enhancement, peak contrast enhancement, washout rate, apparent diffusion coefficient (ADC), and relative ADC were measured. Binary logistic regression and receiver operating characteristic (ROC) curve analysis were employed to assess the diagnostic capability of individual and combined indices for differentiating nasal sinus lymphoma from nasal sinus carcinoma. RESULTS: Sinonasal lymphoma predominantly exhibited type II TIC(n = 20), whereas sinonasal carcinoma predominantly exhibited type III TIC(n = 23). Significant differences were observed in all parameters except washout ratio (p < 0.05), and ADC value emerged as the most reliable diagnostic tool in single parameter. Combined DCE-MRI parameters demonstrated superior diagnostic efficacy compared to individual parameters, with the highest efficiency (area under curve = 0.945) achieved when combining all parameters of DCE-MRI and DWI. CONCLUSIONS: Multiparametric evaluation involving contrast-enhanced dynamic MRI and DWI holds considerable diagnostic value in distinguishing sinonasal lymphoma from sinonasal carcinoma.
Subject(s)
Diffusion Magnetic Resonance Imaging , Lymphoma , Multiparametric Magnetic Resonance Imaging , Paranasal Sinus Neoplasms , Humans , Male , Female , Middle Aged , Diagnosis, Differential , Paranasal Sinus Neoplasms/diagnostic imaging , Lymphoma/diagnostic imaging , Adult , Aged , Case-Control Studies , Diffusion Magnetic Resonance Imaging/methods , Multiparametric Magnetic Resonance Imaging/methods , Contrast Media , Carcinoma/diagnostic imaging , ROC Curve , Sensitivity and Specificity , Young AdultABSTRACT
Cell surface receptors play crucial roles in cellular responses to extracellular ligands, helping to modulate the functions of a cell based on information coming from outside the cell. Syndecan refers to a family of cell adhesion receptors that regulate both extracellular and cytosolic events. Alteration of syndecan expression disrupts regulatory mechanisms in a cell type-specific fashion, often leading to serious diseases, notably cancer. Given the multifaceted functions and distinct tissue distributions of syndecan, it will be important to unravel the gene-level intricacies of syndecan expression and thereby further understand its involvement in various carcinogenic processes. Although accumulating evidence indicates that the protein expression patterns of syndecan family members are significantly altered in cancer cells, the underlying gene-level mechanisms remain largely unknown. This review endeavors to explore syndecan gene expression levels across different cancer types by scrutinizing extensive cancer genome datasets using tools such as cBioPortal. Our analysis unveils that somatic mutations in SDC genes are rare occurrences, whereas copy number alterations are frequently observed across diverse cancers, particularly in SDC2 and SDC4. Notably, amplifications of SDC2 and SDC4 correlate with heightened metastatic potential and dismal prognosis. This underscores the recurrent nature of SDC2 and SDC4 amplifications during carcinogenesis and sheds light on their role in promoting cancer activity through augmented protein expression. The identification of these amplifications not only enriches our understanding of carcinogenic mechanisms but also hints at the potential therapeutic avenue of targeting SDC2 and SDC4 to curb cancer cell proliferation and metastasis.
Subject(s)
Gene Amplification , Humans , Gene Expression Regulation, Neoplastic , Neoplasm Metastasis , Animals , Syndecan-4/genetics , Syndecan-4/metabolism , Syndecans/genetics , Syndecans/metabolism , Carcinoma/genetics , Carcinoma/pathology , Carcinoma/metabolism , Neoplasms/genetics , Neoplasms/pathology , Neoplasms/metabolism , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolismABSTRACT
Mutations affecting codon 172 of the isocitrate dehydrogenase 2 (IDH2) gene define a subgroup of sinonasal undifferentiated carcinomas (SNUCs) with a relatively favorable prognosis and a globally hypermethylated phenotype. They are also recurrent (along with IDH1 mutations) in gliomas, acute myeloid leukemia, and intrahepatic cholangiocarcinoma. Commonly reported mutations, all associated with aberrant IDH2 enzymatic activity, include R172K, R172S, R172T, R172G, and R172M. We present a case of SNUC with a never-before-described IDH2 mutation, R172A. Our report compares the methylation pattern of our sample to other cases from the Gene Expression Omnibus database. Hierarchical clustering suggests a strong association between our sample and other IDH-mutant SNUCs and a clear distinction between sinonasal normal tissues and tumors. Principal component analysis (PCA), using 100 principal components explaining 94.5% of the variance, showed the position of our sample to be within 1.02 standard deviation of the other IDH-mutant SNUCs. A molecular modeling analysis of the IDH2 R172A versus other R172 variants provides a structural explanation to how they affect the protein active site. Our findings thus suggest that the R172A mutation in IDH2 confers a gain of function similar to other R172 mutations in IDH2, resulting in a similar hypermethylated profile.