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【Objective】 To explore the correlation between CSAG1 expression and the prognosis and tumor-infiltrating lymphocytes in renal clear cell carcinoma (RCCC), and to predict the survival and tumor progression. 【Methods】 The gene expression profiles and clinical information of CSAG1 were downloaded from the Cancer Genome Atlas (TCGA). Based on the differential mRNA expression, GO annotation and KEGG pathway analysis were performed. The relationship between CSAG1 and tumor immune infiltration was assessed with Tumor Immunoassay Resource (Timer 2.0) database. The mRNA expression of CSAG1 in human RCCC specimens was validated with qRT-PCR. 【Results】 CSAG1 expression was significantly higher in RCCC tissues than in normal tissues (P<0.05). The qRT-PCR results revealed that the mRNA level of CSAG1 was consistent with that predicted by bioinformatic analysis. The KEGG analysis and GO annotation indicated high GSAG1 expression in RCCC was related to transmembrane transport, tricarboxylic acid cycle and lysosome. CSAG1 expression was positively related to the infiltration of pDC, aDC, CD8+ T cells, cytotoxic cells, TFH, TH1 cells, Tem, NK CD56dm cells, Treg and T cells, but negatively correlated with macrophage infiltration. 【Conclusion】 CSAG1 may be associated with poor prognosis of RCCC and become a potential immunotherapy target.
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Background Kidney renal clear cell carcinoma (KIRC) is one of the most common renal malignancies with a high mortality rate. Cuproptosis, a novel form of cell death, is strongly linked to mitochondrial metabolism and is mediated by protein lipoylation, leading to a proteotoxic stress response and cell death. To date, few studies have ellucidated the holistic role of cuproptosis-related genes (CRGs) in the pathogenesis of KIRC.Methods We comprehensively and completely analyzed the RNA sequencing data and corresponding clinical information from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. We screened for differentially expressed CRGs and constructed a prognostic risk model using univariate and multivariate Cox proportional regression analyses. Kaplan-Meier analysis was performed and receiver operating characteristic (ROC) curves were plotted to predict the prognosis of KIRC patients. Functional enrichment analysis was utilized to explore the internal mechanisms. Immune-related functions were analyzed using single-sample gene set enrichment analysis (ssGSEA), tumour immune dysfunction and exclusion (TIDE) scores, and drug sensitivity analysis.Results We established a concise prognostic risk model consisting of four CRGs (DBT, DLAT, LIAS and PDHB) to predict the overall survival (OS) in KIRC patients. The results of the survival analysis indicated a significantly lower OS in the high-risk group as compared to the patients in the low-risk group. The area under the time-dependent ROC curve (AUC) at 1, 3, and 5 year was 0.691, 0.618, and 0.614 in KIRC. Functional enrichment analysis demonstrated that CRGs were significantly enriched in tricarboxylic acid (TCA) cycle-related processes and metabolism-related pathways. Sorafenib, doxorubicin, embelin, and vinorelbine were more sensitive in the high-risk group.Conclusions We constructed a concise CRGs risk model to evaluate the prognosis of KIRC patients and this may be a new direction for the diagnosis and treatment of KIRC.
Subject(s)
Humans , Carcinoma, Renal Cell/genetics , Immunotherapy , Kidney , Kidney Neoplasms/genetics , Prognosis , Copper , ApoptosisABSTRACT
ABSTRACT Background Autopsy requests have been trending downward for a variety of factors. There are differences between pre- and postmortem diagnoses. Autopsies remain a tool for education, public health research, quality control, and closure for families. Objective We report two cases that illustrate the utility of autopsy for uncovering contributing factors in the death of these patients and highlight their ongoing importance. Design Clinical and autopsy investigation of two individuals and illustration of the importance of autopsy findings which, had they been diagnosed premortem, could have changed the outcome. Cases were evaluated using the Goldman criteria for discrepancies between premortem clinical diagnoses and postmortem autopsy findings. Results In the first case, the patient had been previously admitted due to a non-ST elevation myocardial infarction months before the fatal event. The autopsy showed an undiagnosed clear cell carcinoma of the ovary. She expired due to a massive myocardial infarction secondary to neoplasm induced hypercoagulable state. The degree of pre-mortem/postmortem diagnostic discrepancy makes this a Goldman Class I error. In the second case, the patient presented to the emergency department with symptoms of Guillain-Barré Syndrome (GBS), for which he was treated. Abdominal masses were discovered; however, the patient decompensated before workup was completed. A high-grade B-cell lymphoma was confirmed but would not have altered the outcome, making this a Goldman class II error. Conclusions The autopsy remains a relevant and necessary tool for physicians and society. It assists in the establishment of diagnoses, measurement of treatment quality, the providence of public health metrics, and closure to the survivors.
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Clear cell carcinoma (CCC) of the uterine cervix is a rare gynecologic cancer that accounts for 4–9% of adenocarcinoma of the uterine cervix. Two types of uterine cervical CCCs are known: A type that is associated with in utero exposure to diethylstilbestrol (DES) and idiopathic type that is unrelated to DES exposure. Due to its rare incidence, the clinical behavior and pathological characteristics of CCCs are not fully described and treatment recommendations are not standardized. Moreover, only a few cases are reported on the recurrent metastatic CCCs and the results of various treatment trials are inconsistent. We present a case of successfully treated idiopathic metastatic CCC of the uterine cervix that recurred after concurrent chemoradiotherapy.
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Objective:To analyze the relationship between the expression and prognosis of kinesin family member 4A (KIF4A) in renal clear cell carcinoma and explore its potential mechanism.Methods:Information on the KIF4A gene in renal clear cell carcinoma was retrieved from the UALCAN database, including expression levels, survival analysis, and positive and negative correlation gene data, from which the expression levels, prognostic information, and potential mechanisms of KIF4A in renal clear cell carcinoma were derived.Results:KIF4A is highly expressed in renal clear cell carcinoma, and male patients have a higher expression rate than female patients. The higher the tumor grade and the later the N stage, the more expression ( P<0.05). The survival analysis showed that the expression level and prognosis of KIF4A were negatively correlated ( P<0.05). Cyclin B2 (CCNB2), kinesin family member 23 (KIF23), cell division cycle associated 5 (CDCA5), and KIF4A were significantly positively correlated, whereas DHRS12, crumbs protein homolog 3 (CRB3), β-hydroxybutyrate dehydrogenase 2 (BDH2), and KIF4A were significantly negatively correlated. Conclusions:KIF4A plays an important role in the development of renal clear cell carcinoma and can be used as a potential marker and therapeutic target for the diagnosis and prognosis of renal clear cell carcinoma, including in children.
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Bladder clear cell carcinoma is a rare variant of epithelial carcinoma of the lower urinary tract. This manuscript reported a case of 71-year-old female patient with the main complaint of gross hematuria. Transurethral resection of baldder tumor(TURBT) was performed after Gynecological consultation, and postoperative pathology results revealed clear cell carcinoma in bladder. Four months after surgery, the pelvic CT showed tumor recurrence in bladder. Another TURBT was performed followed with gemcitabine infusion chemotherapy. At 5 months after the second surgery, the tumor recurred again, and also resected by TURBT. No relapse or metastasis occurred during the 5-month follow-up after the third operation.
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Objective:To evaluate the potential effects of serum lipid levels, appendicular skeletal muscle mass index (ASMI) and body mass index (BMI), together with its dynamic changes, on tumor progression in renal clear cell carcinoma patients, so as to inform body weight management.Methods:This prospective cohort study included a total of 100 patients with high-risk clear cell renal cell carcinoma. Serum lipid levels were detected, ASMI and BMI were measured using bioelectrical impedance analysis and the dynamic changes of BMI were tracked. The effects of BMI, ASMI and serum lipid levels on tumor progression within 2 years were explored.Results:Patients with normal BMI and low ASMI had 5.248 (95% CI: 1.946 to 14.153, P = 0.001) times higher risk of tumor progression than those who were overweight or obese. For every 0.1-unit increase in pre-operative HDL-C, the risk of tumor progression decreased by 0.771 (95% CI: 0.631 to 0.942, P = 0.011) times. Patients who experienced more than 5% decrease in BMI compared with baseline had 5.165 (95% CI: 1.735 to 15.370, P = 0.003) times the progression risk of patients whose BMI changed within ±5% from baseline. Conclusions:The advantage of obese clear cell carcinoma patients over normal-weight patients in tumor progression-free survival may be influenced by ASMI, pre-onset involuntary weight loss and lipid levels. Therefore, patient weight management should not merely focus on absolute BMI but tailor to individual characteristics, including cancer stage, body composition and metabolic status.
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Objective To establish a novel defined pyroptosis-related genes risk model of kidney renal clear cell carcinoma. Methods Data of 522 patients with KIRC and 72 normal tissue samples were respectively downloaded from the Cancer Genome Atlas ( TCGA) database and Genotype-Tissue Expression ( GTEx) database. Differential analysis was performed between data of TCGA and GTEx. Univariate Cox regression analysis, multivariate Cox regression analyses and LASSO Cox regression analysis were used to establish a prognostic risk model. Data from the International Cancer Genome Consortium (ICGC) database was used as an external validation cohort. Gene ontology ( GO) enrichment analysis and Kyoto Encylopedia of Genes and Genomes (KEGG) pathway analysis were used to explore the differences of gene functions and pathways between high-risk and low-risk groups. The CIBERSORT database was used to explore the immune infiltration of high-risk and low-risk groups. Results Through differential analysis, we obtained 13 differentially expressed pyroptosis-related genes. Univariate Cox regression analysis, multivariable Cox regression analyses and LASSO Cox regression analysis were used to establish a 6-gene risk model. Kaplan-Meier analysis indicated that survival time in high-risk group was shorter than low-risk group in both cohorts. The area under the curve ( AUC) was 0. 710 for 1-year, 0. 683 for 2-year, and 0. 727 for 3-year survival in the TCGA_KIRC cohort. The AUC was 0. 592 for 1-year, 0. 531 for 2-year, and 0. 545 for 3-year survival in the ICGC_RECA cohort. Independent prognostic analysis indicated that risk score was an independent prognostic factor. GO enrichment analysis and KEGG pathway analysis showed that it was mainly associated with immune and inflammatory responses. The result of tumor immune infiltration showed that the high-risk group had low infiltration levels of regulatory T cells , natural killer cells, monocytes, M2 macrophages and eosinophils and high infiltration level of B cells, CD8+T cells and follicular helper T cells. Conclusion Pyrolysis-related genes may play an important role in KIRC tumor immunity, and the 6-gene risk model can provide a forecast basis for personalized treatment of patients with KIRC.
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【Objective】 To explore and verify the mechanism of curcumin’s inhibition of the proliferation of renal clear cell carcinoma （RCCC） based on network pharmacology and bioinformatics. 【Methods】 We screened common target genes of RCCC and curcumin from PharmMapper and GeneCards databases. We used TCGA database data analysis to screen out common target genes which not only differentially expressed between RCCC tissue samples and normal tissue samples but also affected prognosis. We also used STRING platform to construct curcumin-RCCC targets interaction network， used R software to perform GO biological process analysis and KEGG pathway enrichment analysis based on the above-mentioned screening target proteins. After curcumin and/or active oxygen inhibitor N-acetyl-L-cysteine （NAC） were incubated in renal cancer 786-O and ACHN cells， CCK8 was used to detect the effects of different concentrations of curcumin on cell proliferation and cell viability. Reactive oxygen detection kit （DCFH-DA） was used to detect the level of intracellular reactive oxygen species， and malondialdehyde （MDA） determination kit （TBA method） to detect intracellular malondialdehyde changes. 【Results】 PharmMapper website and GeneCards database screened out 109 common targets of curcumin and RCCC. TCGA database data analysis screened out 37 differentially expressed genes （DEGs） that might affect the overall survival of patients. The core target proteins of curcumin screened out by protein-protein interaction （PPI） that inhibited the biological behavior of RCCC mainly involved CASP3， EGFR， CHEK1， HSP90AA1， and AR. GO enrichment analysis identified 213 items， mainly including reactive oxygen species metabolic process， response to steroid hormones， fibrinolysis and other biologically active processes. KEGG enrichment analysis identified 24 items， which were mainly related to pyruvate metabolism， glycolysis/gluconeogenesis， FoxO signaling pathway， colorectal cancer， tyrosine metabolism， IL-17 signaling pathway， apoptosis and other signaling pathways. Curcumin reduced the cell viability of 786-O and ACHN in a time- and dose-dependent manner （P<0.05）. After curcumin was incubated with kidney cancer cells， the level of reactive oxygen species and MDA increased significantly （P<0.05）. The addition of NAC reversed the effect of curcumin on the cell viability of 786-O and ACHN cells （P<0.05）. 【Conclusion】 Curcumin may participate in the oxidative stress pathway to inhibit the proliferation of renal cell carcinoma.
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【Objective】 To establish a prognostic model of fatty acid metabolism related genes for predicting the prognosis of renal clear cell carcinoma. 【Methods】 The differentially expressed fatty acid metabolism-related genes in renal clear cell carcinoma samples and normal samples in TCGA database were screened by R language software. The Cox proportional hazard regression model was used to select and establish a multigene prognostic model and the prognostic score was calculated. Patients were divided into high-risk group and low-risk group according to the median prognostic score. Kaplan-Meier survival curve was used to analyze the difference in two groups. The clinical pathological factors and prognostic score factors were included in the Cox regression model to analyze the factors affecting the survival of patients with renal clear cell carcinoma. ROC receiver operating curve analysis was used to evaluate the accuracy of the prognostic prediction model. The prognostic model of fatty acid metabolism-related genes and their correlation with clinical factors were analyzed. GSEA enrichment analysis analyzed the differences of gene sets in risk groups. 【Results】 A total of 4 differential genes (CPT1B, HADH, CYP4A11, and ACADSB) were selected to establish a prognostic model for genes related to fatty acid metabolism in renal cell carcinoma. The prognostic risk score (RS) formula is as follows: RS=0.490×CPT1B-0.428×HADH-0.11 × CYP4A11-0.372 × ACADSB. Kaplan-Meier survival analysis confirmed that the overall survival rate of patients with low-risk prognostic score was significantly higher in patients with overall renal clear cell carcinoma, and the difference was statistically significant (P<0.001). Cox regression analysis showed that the prognostic model of genes related to age and fatty acid metabolism is an independent influencing factor for the prognosis of patients with renal clear cell carcinoma (P<0.01). The 5 years’ AUC of the renal clear cell carcinoma ROC curve of the renal cancer fatty acid metabolism related gene model was 0.802. GSEA analysis showed that the difference of 81 gene sets in the low-risk group was statistically significant (P<0.05). 【Conclusion】 The prognostic model of renal cancer fatty acid metabolism-related genes can be used to predict the prognosis of patients with renal clear cell carcinoma, which is conducive to further guide clinical treatment.
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Renal collecting duct carcinoma(CDC) is rare in clinic, complicated with clear cell renal cell carcinoma(ccRCC) of one kidney is extremely rare. We reported a case CDC complicated with ccRCC of one kidney. The patient was admitted as left low back pain and gross hematuria, preoperative CT examination showed that one tumor was found in the upper middle pole and another tumor at lower pole of the left kidney, and multiple enlarged lymph nodes in the medial edge of the kidney. CT diagnosis was renal collecting duct carcinoma complicated with clear cell carcinoma of the left kidney, retroperitoneal lymphatic metastasis and underwent radical nephrectomy. Postoperative pathological diagnosis was CDC(upper middle pole) complicated with ccRCC(lower pole)of the left kidney. The patients were treated with sunitinib for 6 months and survived 13 months, and died of extensive metastasis.
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The metastasis of renal cell carcinoma to the ureter is a rare phenomenon, and synchronal detection of metastasis to the contralateral ureter is a rarer phenomenon. A 62-year-old male patient with painless hematuria was examined and detected a renal cell carcinoma on the right kidney and bleeding from the left ureter. Ureteroscopy revealed a tumor in the left upper ureter, and biopsy suggested clear cell carcinoma. Laparoscopic radical nephrectomy was performed to resect the right renal cell carcinoma, and the pathology revealed a clear cell carcinoma, with Fuhrman nuclear grade 2 class. The ureteral tumor was resected 3 months later and the pathology revealed renal clear cell carcinoma. Sunitinib was used for 37 months, and there was no tumor recurrence or metastasis so far.
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Background: Alpha-methylacyl-coenzyme A racemase (AMACR, P504S) is a commonly used marker in immunohistochemical diagnosis of prostate cancer. Recent studies identified P504S markers of the clear cell histotype in the ovary and/or endometrium. Gastric-type adenocarcinoma (GAS) is difficult to diagnose histologically, particularly when there is crossover with clear cell carcinoma (CCC). However, the significance of P504S for differentially diagnosing GAS and CCC is unclear. Aim: To evaluate P504S as a potential diagnostic marker of GAS and CCC. Settings and Design: We analyzed P504S expression in 48 cervical carcinomas (32 GAS and 16 CCC), as well as the expression of other markers including hepatocyte nuclear factor-1 beta (HNF-1?) and NapsinA. Material and Methods: The expression differences of HNF-1?, NapsinA, and P504S in GAS and CCC were detected by immunohistochemistry. Immunohistochemical histoscores based on the intensity and extent of staining were calculated. Results: The positive rates of HNF-1? in GAS and CCC were 90.32% and 75%, respectively. (?2 = 2.251, P = 0.663). The positive rates of NapsinA in GAS and CCC were 19.36% and 81.25%, respectively. (?2 = 47.332, P < 0.01). The positive rates of P504S in GAS and CCC were 16.13% and 81.25%, respectively. (?2 = 41.420, P < 0.01). HNF-1? was frequently expressed in GAS and CCC, while NapsinA and P504S were frequently expressed in CCC, and reduced or lost in GAS. Conclusion: NapsinA and P504S can be used to differentiate between GAS and CCC.
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Metastatic seminal vesicle carcinoma is rare in clinic. The case of renal clear cell carcinoma metastasis to the seminal vesicle gland is more rare, which is difficult to be identified with bladder, prostate and colorectal tumors. In November 2017, 1 case of renal clear cell carcinoma metastasis to the left side of the seminal vesicle gland was admitted in our hospital.Laparoscopy seminal vesicle metastasis tumor resection was performed. Regular bladder irrigation and sunitib oral intake were conducted. No evidence of local recurrence was found within 19 months follow-up.
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@#Hyalinizing clear cell carcinoma presents as a painless submucosal mass commonly located at the palate and base of tongue. It is a rare tumour and has often been misdiagnosed for other more common tumours with clear cytoplasm, such as acinic cell carcinoma, clear cell oncocytoma or mucoepidermoid carcinoma. HCCC has been reported as a low grade malignant tumour with a high rate of cervical metastases. Due to its rarity, there is no treatment protocol. However, the treatment of choice is wide local excision and the neck disease is treated with neck dissection or radiotherapy or both with no conclusive outcome as incidence is too low or underreported with no long term follow up. Our case highlights the diagnosis difficulties in such rare cases, and the need for longer follow up post excision to determine outcome and recurrence rates.
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Metastatic seminal vesicle carcinoma is rare in clinic.The case of renal clear cell carcinoma metastasis to the seminal vesicle gland is more rare,which is difficult to be identified with bladder,prostate and colorectal tumors.In November 2017,1 case of renal clear cell carcinoma metastasis to the left side of the seminal vesicle gland was admitted in our hospital.Laparoscopy seminal vesicle metastasis tumor resection was performed.Regular bladder irrigation and sunitib oral intake were conducted.No evidence of local recurrence was found within 19 months follow-up.
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@#A 24-year-old male presented with worsening right buccal pain and numbness of the anterior right tip of the tongue. A fixed, hard, non-tender mass was found on the right floor of the mouth. Subsequently, maxillofacial surgery evaluation, MRI scan of the head and neck, and biopsy confirmed a low-grade hyalinising clear cellcarcinoma, likely of salivary gland origin. This clinical encounter led to a review for the variety of masses that can occur in each site in the oral cavity and the commonmasses that may present to a GP. A suggested management approach is presented. In addition,common salivary gland pathologies are highlighted, andsalivary gland tumours as was present in this patient are further discussed.
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O adenocarcinoma de células claras (CCA) primário de colo uterino em pacientes jovens é uma doença rara, de etiologia desconhecida e que no passado estava associada ao uso do dietilestilbestrol durante a gestação, quando sua comercialização era permitida. A queixa mais frequente do CCA é o sangramento vaginal irregular. Relatamos o caso de CCA de endocérvice em paciente jovem que engravidou naturalmente após o diagnóstico da neoplasia.(AU)
Primary cervical clear cell adenocarcinoma (CCA) in young patients is a rare disease of unknown etiology in the past associated with the use of diethylstilbestrol during pregnancy when its use was permitted. The most frequent complaint is irregular vaginal bleeding. We report the case of endocervous clear cell adenocarcinoma in a young patient who became naturally pregnant, even after the diagnosis of the neoplasia.(AU)
Subject(s)
Humans , Female , Pregnancy , Adult , Pregnancy Complications/physiopathology , Adenocarcinoma, Clear Cell , Pregnancy, High-RiskABSTRACT
Clear cell carcinoma of ovary is a rare tumour with a very low incidence in pregnancy. It is attributed to develop from an existing background of endometriosis. There are very few case reports of the above combination tumours in pregnancy. It is a very aggressive tumour with a worse prognosis and low survival rate because of its peculiar chemo resistant nature. Early detection and effective treatment are the best approach. The treatment options for advanced stages are still under research.
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Although cancers of rectum and kidney are common malignancies, the occurrence of primary synchronous neoplasms of these organs has been reported rarely. Very few case reports are available in literature till date. The relationship between these two events remains unclear, probably because of the rarity of the association. In this report, we describe incidentally detected renal cell carcinoma in an elderly man, during staging workup of rectal adenocarcinoma and both malignancies were surgically managed simultaneously with curative intent.