Comprehensive Analysis of the Value of SMYD Family Members in the Prognosis and Immune Infiltration of Malignant Digestive System Tumors
Donghui LiuXuyao WangEnhong ShiLiru WangMing-hao NieLong LiQingxin JiangPengyu KongShuai ShiChao WangSen YanZhihui QinShuang Zhao
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The SET and MYND domain-containing (SMYD) gene family comprises a set of genes encoding lysine methyltransferases. This study aimed to clarify the relationship between the expression levels of SMYD family members and the prognosis and immune infiltration of malignant tumors of the digestive system.The Oncomine, Ualcan, Kaplan-Meier Plotter, cBioPortal, Metascape, and TIMER databases and tools were used to analyze the correlation of SMYD family mRNA expression, clinical stage, TP53 mutation status, prognostic value, gene mutation, and immune infiltration in patients with esophageal carcinoma (ESCA), liver hepatocellular carcinoma (LIHC), and stomach adenocarcinoma (STAD).In ESCA, the mRNA expression of SMYD2/3/4/5 was significantly correlated with the incidence rate, that of SMYD2/3 with the clinical stage, that of SMYD2/3/4/5 with TP53 mutation status, that of SMYD2/4/5 with overall survival (OS), and that of SMYD1/2/3/4 with relapse-free survival (RFS). In LIHC, the mRNA expression of SMYD1/2/3/4/5 was significantly correlated with the incidence rate, that of SMYD2/4/5 with the clinical stage, that of SMYD3/5 with TP53 mutation status, that of SMYD2/3/4/5 with OS, and that of SMYD3/5 with RFS. In STAD, the mRNA expression of SMYD2/3/4/5 was significantly correlated with the incidence rate, that of SMYD1/4 with the clinical stage, that of SMYD1/2/3/5 with TP53 mutation status, that of SMYD1/3/4 with OS, and that of SMYD1/3 with RFS. Furthermore, the function of SMYD family mutation-related genes in ESCA, LIHC, and STAD patients was mainly related to pathways, such as mitochondrial gene expression, mitochondrial matrix, and mitochondrial translation. The expression of SMYD family genes was significantly correlated with the infiltration of six immune cell types and eight types of immune check sites.SMYD family genes are differentially expressed and frequently mutated in malignant tumors of the digestive system (ESCA, LIHC, and gastric cancer). They are potential markers for prognostic prediction and have important significance in immunity and targeted therapy.Keywords:
Retinoblastoma
The authors analyze the pathohistological archives of the Tashkent Research Institute of Ophthalmic Diseases for the years 1985-1994 and their own materials collected in recent years: 44 eyes enucleated for retinoblastoma. The microscopic picture of 44 tumors is as follows: retinoblastoma A in 12 (27.3%) cases, retinoblastoma B in 16 (36.3%), retinoblastoma C in 9 (20.4%), and mixed form in 7 (16%) cases. The total level of retinoblastoma A and B is almost 64%; this condition is positively life-threatening. The authors emphasize the necessity of health education of the population and improvement of primary health care and prophylactic check-ups of preschool children.
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Purpose of review Retinoblastoma is a pediatric eye tumor that serves as a paradigm for understanding the genetic basis of cancer. This review will highlight recent advances in retinoblastoma genetic research and discuss how these new findings influence our knowledge of retinoblastoma tumorigenesis and management. Recent findings Current data demonstrate that retinomas, benign retinal tumors found in some retinoblastoma patients, exhibit bi-allelic mutations in RB1, the retinoblastoma gene, and lack of expression of the retinoblastoma protein. Interestingly, retinomas demonstrate a low level of genomic instability that becomes progressively more severe in retinoblastoma tumors. Additionally, a subset of retinomas share genomic alterations with retinoblastoma. Collectively, these data suggest that retinomas represent true premalignant lesions and not regressed retinoblastoma tumors, as previously thought. Translational advances in retinoblastoma genetic research include development of an allele-specific assay that now enables the identification of mutational mosaicism, thereby increasing the rate of RB1 mutation detection in bilaterally affected patients to as high as 95%. Summary These and related research efforts reveal novel data that enhance our understanding of the biology of retinoblastoma. These observations may facilitate new therapeutic approaches to further decrease the morbidity and mortality associated with retinoblastoma and other more common forms of cancer.
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In recent years, the treatment concept of retinoblastoma has changed from focusing on saving children's life to preserving the eyeballs and useful visual function. As a promising way to retain the eyeball, the application of vitrectomy in patients with retinoblastoma has long been debated. In view of the special anatomical structure of eyes and the biological characteristics of retinoblastoma cells, retinoblastoma is always prone to recurrence and metastasis after vitrectomy. Therefore, vitrectomy could hardly be a routine treatment and it should be used in retinoblastoma patients cautiously. (Chin J Ophthalmol, 2018, 54: 649-651).近年来视网膜母细胞瘤（RB）的治疗理念已从关注保护患者的生命转变为尽可能保留患者的眼球和有用视功能。玻璃体切除术作为一种保留眼球的治疗方式，是否可以应用于RB的治疗一直存在很大争议。鉴于眼球特殊的解剖结构及RB细胞的生物学特性，本文通过分析玻璃体切除术治疗RB存在的问题以及术后复发性RB的组织病理学改变，指出RB患者进行玻璃体切除术存在较高的肿瘤复发及转移风险，玻璃体切除术不宜作为RB的常规治疗方式，应审慎选择玻璃体切除术治疗RB。（中华眼科杂志，2018，54：649-651）.
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Of 726 eyes consecutively enucleated at the Mayo Clinic from 1954 through 1974, 41 contained retinoblastoma. In no instance was unsuspected retinoblastoma identified, nor could retinoblastoma be confirmed pathologically in an additional eight eyes in which retinoblastoma was considered in the differential diagnosis. In each of our eight misdiagnosed cases, the eyes were already blind and were cosmetically defective. The frequency of clinical misdiagnosis of retinoblastoma is high in part because it must be considered in every case of leukokoria. Although every effort was made to arrive at an accurate clinical diagnosis, the clinical misdiagnosis of retinoblastoma in a blind eye is of far less serious consequence than the clinical misdiagnosis of a tumor in a seeing eye.
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Objective To investigate the siginificance of Fas/FasL and p53 expression in retinoblastoma.Methods FasL,Fas and bcl 2 were detected immunohistochemically in 45 cases of retinoblastoma and 12 cases of normal retina.Results The expression of Fas in retinoblastoma and normal retina were very low with no difference( P 0.05).The expression of FasL in retinoblastoma and normal retina were high,but with no significantly difference( P 0.05).p53 was highly expressed in retinoblastoma and low expressed in normal retina,with significant difference( P 0.0002).Conclusion High expression of FasL and low expression of Fas in retinoblastoma and normal retina suggested that they might be associated with immune escape.The high expression of p53 in retinoblastoma was closely associated with the tumor development.\;
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Human retinoblastoma is caused by mutational inactivation of the retinoblastoma suppressor gene (RB). We have examined intraocular tumorigenicity of retinoblastoma cells in which RB expression was achieved by retroviral transduction. Retinoblastoma cells were injected into the anterior chambers of severe combined immunodeficient mouse eyes, and tumorigenicity was assessed. RB-expressing retinoblastoma cells usually failed to form progressive tumors in the anterior chamber, whereas the parental, RB-negative line, WERI-Rb27, was rapidly tumorigenic. These results support the hypothesis that inactivation of the RB gene is critical for the growth of retinoblastoma tumors. The potential use of RB reconstitution for treating human retinoblastoma is suggested by our finding that intraocular tumor growth can be suppressed by RB expression.
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Objective To investigate the significant of Fas and bcl?2 expression in retinoblastoma.Methods The immunohistochemical staining was performed to detect Fas and bcl?2 in 45 cases of retinoblastoma and 12 cases of normal retina.Results The expression of Fas in retinoblastoma and normal retina were 0.255±0.441 and 0.083±0.289 respectively ( P =0.114?8).bcl?2 was high in retinoblastoma 2.702± 1.082 and low in normal retina 0.167±0.389,showing significant difference( P 0.000?1).Conclusion Low regulation of Fas expression in retinoblastoma and normal retina suggested that it is a throughout event which prohibit the apoptosis. The high expression of bcl?2 in retinoblastoma was close associated with the tumour development.
Retinoblastoma
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