TSC2 nonsense mutation in angiomyolipoma with epithelial cysts: a case report and literature review.

Background: Angiomyolipoma with epithelial cysts (AMLEC) is an extremely rare subtype of kidney angiomyolipoma that contains epithelial-lined cysts. The most distinctive immunohistochemical feature of AMLEC is its immunoreactivity with melanocytic markers. AMLEC also has a distinct histological structure, which aids in its pathological diagnosis. To date 27 cases of AMLEC have been reported in 11 case series. However, the molecular biology underlying the pathogenesis of AMLEC remains unexplored. Case report: A 30-year-old female was diagnosed with AMLEC and underwent partial nephrectomy. Histologically, the cross-section of cystic tissue revealed a multilocular appearance, with some cysts containing thrombus-like material, and the wall thickness was approximately 0.2 ~ 0.3 cm. Additionally, the compact subepithelial cellular stroma showed strong and diffuse nuclear labeling for estrogen receptor, progesterone receptor, and CD10, as well as HMB45 and Melan A, which are markers of melanocytic differentiation. Furthermore, using a DNA targeted sequencing panel with next-generation sequencing, we identified a nonsense mutation in TSC Complex Subunit 2 (TSC2) gene, resulting in the formation of a premature termination codon. Moreover, the mutated genes found to be enriched in the PI3K-AKT pathway. The patient in this case had a favorable postoperative follow-up at 3 months. Conclusion: To the best of our knowledge, this study represents the first analysis of genotype mutations in AMLEC, providing valuable insights for future clinical practice. These findings have significant potential in guiding the understanding and management of AMLEC, paving the way for further research and advancements in the field.

Exploring the Diagnostic and Prognostic Predictive Values of Ferroptosis- Related Markers in Lung Adenocarcinoma.

BACKGROUND: Lung Adenocarcinoma (LUAD), a common and aggressive form of lung cancer, poses significant treatment challenges due to its low survival rates. AIM: To better understand the role of ferroptosis driver genes in LUAD, this study aimed to explore their diagnostic and prognostic significance, as well as their impact on treatment approaches and tumor immune function in LUAD. METHOD: To accomplish the defined goals, a comprehensive methodology incorporating both in silico and wet lab experiments was employed. A comprehensive analysis was conducted on a total of 233 ferroptosis driver genes obtained from the FerrDB database. Utilizing various TCGA databases and the RT-qPCR technique, the expression profiles of 233 genes were examined. Among them, TP53, KRAS, PTEN, and HRAS were identified as hub genes with significant differential expression. Notably, TP53, KRAS, and HRAS exhibited substantial up-regulation, while PTEN demonstrated significant down-regulation at both the mRNA and protein levels in LUAD samples. The dysregulation of hub genes was further associated with poor overall survival in LUAD patients. Additionally, targeted bisulfite-sequencing (bisulfite-seq) analysis revealed aberrant promoter methylation patterns linked to the dysregulation of hub genes. RESULT & DISCUSSION: Furthermore, hub genes were found to participate in diverse oncogenic pathways, highlighting their involvement in LUAD tumorigenesis. By leveraging the diagnostic and prognostic potential of ferroptosis driver hub genes (TP53, KRAS, PTEN, and HRAS), significant advancements can be made in the understanding and management of LUAD pathogenesis. CONCLUSION: Therapeutic targeting of these genes using specific drugs holds great promise for revolutionizing drug discovery and improving the overall survival of LUAD patients.

Improvement in the performance of an autoantibody panel in combination with heat shock protein 90a for the detection of early­stage lung cancer.

The early diagnosis of lung cancer is closely associated with the decline of mortality. A panel consisting of seven lung cancer-related autoantibodies (7-AABs) has been shown to be a reliable and specific indicator for the early detection of lung cancer, with a specificity of ~90% and a positive predictive value of ~85%. However, its low sensitivity and negative predictive value limit its wide application. To improve its diagnostic value, the diagnostic efficiencies of 7-AABs in combination with non-specific tumor markers were retrospectively investigated for the detection of early-stage lung cancer. A total of 217 patients with small lung nodules who presented with ground-glass opacity or solid nodules as well as 30 healthy controls were studied. The concentrations of 7-AABs and heat shock protein 90a (HSP90a) were assessed using ELISA. Automated flow fluorescence immune analysis was used for the assessment of CEA, CYFRA21-1, CA199 and CA125 levels. The results showed that 7-AABs + HSP90a possessed a remarkably improved diagnostic efficiency for patients with small pulmonary nodules or for patients with lung nodules of different types, which suggested that 7-AABs in combination with HSP90a could have a high clinical value for the improvement of the diagnostic efficiency of early-stage lung cancer.

Hsa_circ_0040809 regulates colorectal cancer development by upregulating methyltransferase DNMT1 via targeting miR-515-5p.

BACKGROUND: Circular RNAs (circRNAs) are key regulators in the progression of various cancers. Abnormal DNA methylation patterns feature prominently in the regulation of the expression of tumor-related genes. This study is aimed at investigating the molecular mechanism of circ_0040809 affecting colorectal cancer (CRC) progression by regulating DNA methyltransferase 1 (DNMT1). METHODS: circ_0040809 was selected from the circRNA microarray datasets (GSE142837 and GSE138589). Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to examine the expression of circ_0040809, miR-515-5p, and DNMT1 mRNA in paired cancerous and paracancerous tissues of 40 CRC patients, as well as in cell lines. Western blotting was conducted for detecting DNMT1 protein expression in CRC cells. Cell proliferation, migration, and apoptosis were assessed through CCK-8, Transwell, and flow cytometry assays. Bioinformatics and dual-luciferase gene assay were conducted to predict and verify, respectively, the targeted relationships between circ_0040809 and miR-515-5p, as well as between miR-515-5p and DNMT1 mRNA. RESULTS: In CRC tissues and cells, circ_0040809 and DNMT1 expression are markedly increased, whereas miR-515-5p expression is decreased. Also, high circ_0040809 expression is significantly linked to shorter overall survival. Cell function compensation experiments reveal that circ_0040809 silencing inhibits CRC cell proliferation and migration and promotes apoptosis, while circ_0040809 overexpression has the opposite effects. Mechanistically, circ_0040809 competitively binds to miR-515-5p to elevate DNMT1 expression. Rescue assay reveals that overexpressed miR-515-5p partly counteracts the tumor-facilitating impact of circ_0040809. CONCLUSIONS: circ_0040809 facilitates CRC cell proliferation and migration, and inhibits apoptosis, through modulating miR-515-5p/DNMT1 axis. Our study implies that targeting circ_0040809 may be a therapy strategy for CRC treatment.

CXCL11 Correlates With Antitumor Immunity and an Improved Prognosis in Colon Cancer.

The chemokine ligand C-X-C motif chemokine ligand 11 (CXCL11) is involved in the progression of various cancers, but its biological roles in colorectal cancer (CRC) remain confused. Therefore, the prognostic value and underlying mechanism of CXCL11 in CRC were preliminarily evaluated. Three independent datasets were used for mRNA-related analysis: one dataset from the Cancer Genome Atlas (TCGA, n = 451) and two single-cell RNA sequencing (scRNA-seq) datasets from Gene Expression Omnibus (GEO): GSE146771 and GSE132465. In addition, a colon adenocarcinoma (COAD) patient cohort (the Yijishan Hospital cohort, YJSHC, n = 108) was utilized for analysis of cell infiltration by immunohistochemistry. We determined the distribution of CXCL11 in tumor tissue across all TCGA cancers and found that CXCL11 expression was significantly upregulated in both COAD and rectal adenocarcinoma (READ). However, the upregulation of CXCL11 mRNA was associated with a better prognosis in COAD, but not in READ. Within the YJSHC, the patients with a high abundance of intratumoral CXCL11+ cells had prolonged survival (p = 0.001). Furthermore, we found that the high CXCL11 expression group had a higher proportion of antitumor immune cells, and a lower proportion of protumor immune cells. Additionally, we discovered the changes of gene expression and enriched immune pathway network mediated by CXCL11. Interestingly, both cytotoxic genes (IFNG, GZMA, GZMB, GZMK, GZMM, and PRF1) and immunosuppressive molecules, including PD-L1, were positively correlated with CXCL11 expression. CXCL11, which promoted antitumor immunity to benefit survival, was identified as an independent prognostic biomarker in patients with COAD.

Elevated Glutathione Peroxidase 2 Expression Promotes Cisplatin Resistance in Lung Adenocarcinoma.

The aim of this study was to explore the roles of GPX2, a member of the glutathione peroxidase family (GPXs, GSH-Px), in cisplatin (DDP) resistance in lung adenocarcinoma (LUAD). GPX2 was found to be the most significantly upregulated gene in a DDP-resistant A549/DDP cell line compared with the parental A549 cell line by RNA sequencing. The knockdown of GPX2 expression in A549/DDP cells inhibited cell proliferation in vitro and in vivo, decreased the IC50 values of DDP, induced apoptosis, inhibited the activities of GSH-Px and superoxide dismutase (SOD), inhibited ATP production and glucose uptake, and increased malondialdehyde (MDA) and reactive oxygen species (ROS) production; while GPX2 overexpression in A549 cells resulted in the opposite effects. Using gene set enrichment analysis (GSEA), we found that GPX2 may be involved in DDP resistance through mediating drug metabolism, the cell cycle, DNA repair and energy metabolism, and the regulation of an ATP-binding cassette (ABC) transporters member ABCB6, which is one of the hallmark genes in glycolysis. Moreover, immunohistochemistry revealed that GPX2 was upregulated in 58.6% (89/152) of LUAD cases, and elevated GPX2 expression was correlated with high expression of ABCB6, high 18-fluorodeoxyglucose (18F-FDG) uptake, and adverse disease-free survival (DFS) in our cohort. The Cancer Genome Atlas (TCGA) data also indicated that GPX2 expression was higher in LUAD than it was in normal lung tissues, and the mRNA expression levels of GPX2 and ABCB6 were positively correlated. In conclusion, our study demonstrates that GPX2 acts as oncogene in LUAD and promotes DDP resistance by regulating oxidative stress and energy metabolism.

Upregulation of HOXA10 Protein Expression Predicts Poor Prognosis for Colorectal Cancer.

AIMS: The homeobox (HOX) genes function as transcriptional factors that can promote tumorigenesis. However, the expression profile of HOXA10 and the role this protein plays in solid tumors are unclear. Here we examined HOXA10 protein expression in samples from colorectal cancer (CRC) patients to address the clinical significance of this protein. MATERIALS AND METHODS: Seven independent investigations from the Oncomine database were retrieved. A total of 85 patients who underwent radical excision followed by 5-fluorouracil (5-FU)-based adjuvant chemotherapy were enrolled. Immunohistochemistry was performed on pairs of cancerous and normal tissues to detect the expression of both HOXA10, and the phosphatase and tensin homolog deleted on chromosome ten (PTEN). Lentivirus-mediated RNA interference was used to knock down HOXA10 expression in LoVo and HT-29 cell lines, then cells' proliferation, apoptosis, and tumor growth in vivo were detected. RESULTS: Oncomine data showed that HOXA10 expression was significantly upregulated in CRC tissues compared with relevant normal controls. In our study, 58 cases (68.2%) showed positive HOXA10 protein expression in tumor tissue and negative expression in normal tissues. HOXA10 protein upregulation was consistent with PTEN downregulation. Although not related to clinicopathological parameters, a significant correlation was found between HOXA10 upregulation and a decreased 5-year disease-free survival (DFS). A Cox proportional hazards model further suggested that HOXA10 overexpression was an independent factor to predict DFS of CRC patients. Furthermore, HOXA10 knockdown significantly increased sensitivity to 5-FU chemotherapy in vitro and in vivo. CONCLUSIONS: Significant HOXA10 overexpression in CRC may be a potential biomarker indicating poor prognosis and 5-FU resistance.

Decreased expression of PinX1 protein predicts poor prognosis of colorectal cancer patients receiving 5-FU adjuvant chemotherapy.

Previous studies suggest that Pin2/TRF1 interacting protein X1 (PinX1) is an intrinsic telomerase inhibitor and a putative tumor suppressor gene in human cancers. The aims of this study were to investigate PinX1 expression status in colorectal cancer (CRC) specimens and to clarify its clinical significance. A total of 83 CRC patients treated with radical resection and 5-fluorouracil (5-FU) based adjuvant chemotherapy were enrolled in this study. Immunohistochemistry was used to detect PinX1 and human telomerase reverse transcriptase (hTERT) protein expression in paired tumor and adjacent normal tissues. Results showed that PinX1 expression was significantly reduced in tumor tissues as compared to normal tissues, the rate of PinX1 protein low/negative expression in CRC and normal tissues was 43.4% (36/83) and 9.6% (8/83), respectively (P<0.001), while hTERT protein expression was upregulated in CRC and negative correlated with PinX1 expression. Although no correlations with clinicopathological features, PinX1 downregulation was significantly associated with adverse 5-year overall survival (OS) and disease-free survival (DFS). Cox proportional hazards model further revealed that PinX1 expression was an independent factor in predicting OS and DFS for CRC patients, apart from lymph metastasis. In conclusion, PinX1 protein expression is decreased in CRC, which may be a new promising tumor marker for CRC prognosis and 5-FU chemosensitivity.

Mesothelial/monocytic incidental cardiac excrescence: a case report and review of literature.

Mesothelial/monocytic incidental cardiac excrescence (MICE) is a rare and distinctive benign lesion often found during cardiac valve replacement. To date, 43 cases have been reported in the English literature. This lesion is important because of the potential for confusion with primary or metastatic malignancy. We report a case of MICE in a 47-year-old Chinese man with rheumatic heart disease whose MICE was discovered during mitral and aortic valve replacement. Histopathological examination of the lesion combined with immunohistochemistry confirmed the diagnosis of MICE.

Methylation of DLEC1 promoter is a predictor for recurrence in Chinese patients with gastric cancer.

PURPOSE: To investigate promoter methylation in the deleted in lung and esophageal cancer 1 (DLEC1) gene in Chinese patients with gastric cancer. METHODS: A total of 227 patients with gastric cancer were enrolled. The methylations of the promoter regions of DLEC1 and ACTB were determined using quantitative methylation-specific PCR. The DLEC1 methylation was compared to the clinicopathological variables of gastric cancer. RESULTS: DLEC1 methylation was not associated with the clinicopathological variables of gastric cancer. Patients with DLEC1-hypermethylated gastric cancer had significantly higher recurrence rate than those with DLEC1-hypomethylated gastric cancer (P = 0.025; hazard ratio = 2.43). CONCLUSIONS: Methylation of DELC1 promoter may be a valuable predictor for recurrence in Chinese patients with gastric cancer.

CDH13 and FLBN3 gene methylation are associated with poor prognosis in colorectal cancer.

The aim of this study was to identify potential epigenetic prognostic biomarkers for colorectal cancer (CRC) in the Chinese population. The methylation status of five tumor suppressor genes (CDH13, DLEC1, FBLN3, hMHL1 and RUNX3) was determined using manual microdissection followed by methylation-specific PCR in 85 paired CRC specimens and adjacent normal tissue. The results showed that methylation frequencies in cancerous tissues were 31.8% for CDH13, 37.6% for DLEC1, 38.8% for FBLN3, 22.4% for hMHL1 and 27.1% for RUNX3, all of which were significantly higher than in corresponding normal tissue. Furthermore, CDH13 methylation was associated with poor differentiation (P = 0.019) and tended to be predominant in advanced stages (P = 0.084); FBLN3 methylation was associated with advanced stages (P = 0.027) and lymph node metastasis (P = 0.029). Accordingly, the methylation status of CDH13 (P = 0.022), FBLN3 (P = 0.008), CDH13 and/or FBLN3 (P = 0.001) predicted adverse overall survival in CRC, while hMHL1 methylation showed a protective role in survival (P = 0.046). Cox proportional hazard models further indicated that CDH13 and/or FBLN3 methylation, but not that of hMHL1, was an independent prognostic factor for CRC. In conclusion, we found CDH13 and FBLN3 gene methylation are potential biomarkers for poor prognosis in CRC.

Effects of osteopontin downregulation on the growth of prostate cancer PC-3 cells.

Osteopontin (OPN) has been recognized as a significant cytokine in the processes of tumorigenicity, tumor progression and metastasis in many types of human cancer. However, the functions of OPN in prostate cancer remain poorly understood. To investigate the function of OPN in human prostate cancer, the growth of prostate cancer PC-3 cells was examined following OPN down-regulation by RNA interference (RNAi). PC-3 cells were transfected by two constructs containing short interfering RNAs designed to cleave two different regions of OPN mRNA. The expression of OPN in the transfected cells was markedly inhibited by RNAi at the mRNA and protein levels. Cell growth was retarded and S-phase arrest and apoptosis were observed in the transfected cells. The number and size of the colonies of the transfected cells in soft agarose were markedly decreased, as compared with those of the control cells. From these results, we conclude that the selective down-regulation of OPN expression by RNAi may lead to S-phase arrest, apoptosis and a decline in the malignant phenotype in PC-3 cells, suggesting that OPN plays a significant role in the growth of prostate cancer and may be a potential therapeutic target.

[Effects of Se-methylselenocysteine on biological behavior of and matrix metalloproteinase-2 expression in human breast cancer MDA-MB-231 cells].

BACKGROUND & OBJECTIVE: Se-methylselenocysteine (MSC), a natural organoselenium compound, has functions on chemoprevention and treatment of many tumors, but the mechanism remains unclear. This study was to investigate the effects of MSC on the biological behavior of and matrix metalloproteinase-2 (MMP-2) expression in human breast cancer MDA-MB-231 cells. METHODS: After treatment of MSC, the proliferation and apoptosis of MDA-MB-231 cells were detected with light microscope and Cell Counting Kit-8 (CCK-8), cell cycle and apoptosis were determined by flow cytometry, malignant phenotype was determined by soft agarose growth assay, and the expression of MMP-2 was determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. The concentration of MMP-2 protein in culture supernatant was measured with enzyme-linked immunosorbent assay (ELISA). RESULTS: MSC induced S phase arrest and apoptosis, inhibited the proliferation and colony formation of MDA-MB-231 cells. When treated with 50 mumol/L MSC for 48 h and 72 h, the mRNA levels of MMP-2 were up-regulated by 32.2% and 47.1%, whereas its protein levels were down-regulated by 42.4% and 50.8%, its concentrations in culture supernatant were down-regulated by 56.7% and 75.2%. When treated with 100 mumol/L MSC for 48 h and 72 h, the mRNA levels of MMP-2 were up-regulated by 52.6% and 61.3%, whereas its protein levels were down-regulated by 72.9% and 81.4%, and its concentrations in culture supernatant were down-regulated by 68.5% and 80.9%. CONCLUSIONS: MSC could inhibit proliferation, and induce apoptosis and S phase arrest in MDA-MB-231 cells. MSC could also up-regulate the mRNA level of MMP-2 while down-regulate its protein level and secretion in the cells.