Anoikis resistance regulates immune infiltration and drug sensitivity in clear-cell renal cell carcinoma: insights from multi omics, single cell analysis and in vitro experiment.

Background: Anoikis is a form of programmed cell death essential for preventing cancer metastasis. In some solid cancer, anoikis resistance can facilitate tumor progression. However, this phenomenon is underexplored in clear-cell renal cell carcinoma (ccRCC). Methods: Using SVM machine learning, we identified core anoikis-related genes (ARGs) from ccRCC patient transcriptomic data. A LASSO Cox regression model stratified patients into risk groups, informing a prognostic model. GSVA and ssGSEA assessed immune infiltration, and single-cell analysis examined ARG expression across immune cells. Quantitative PCR and immunohistochemistry validated ARG expression differences between immune therapy responders and non-responders in ccRCC. Results: ARGs such as CCND1, CDKN3, PLK1, and BID were key in predicting ccRCC outcomes, linking higher risk with increased Treg infiltration and reduced M1 macrophage presence, indicating an immunosuppressive environment facilitated by anoikis resistance. Single-cell insights showed ARG enrichment in Tregs and dendritic cells, affecting immune checkpoints. Immunohistochemical analysis reveals that ARGs protein expression is markedly elevated in ccRCC tissues responsive to immunotherapy. Conclusion: This study establishes a novel anoikis resistance gene signature that predicts survival and immunotherapy response in ccRCC, suggesting that manipulating the immune environment through these ARGs could improve therapeutic strategies and prognostication in ccRCC.

Immunotherapeutic Value of Transcription Factor 19 (TCF19) Associated with Renal Clear Cell Carcinoma: A Comprehensive Analysis of 33 Human Cancer Cases.

Background: We aimed to study the relationship between transcription factor 19 (TCF19) and cancer immunotherapy in the 33 types of human cancers. Methods: The Cancer Genome Atlas database was analyzed to obtain the gene expression data and clinical characteristics for the cases of 33 types of cancers. GSE67501, GSE78220, and IMvigor 210 were included in the immunotherapy cohorts. Relevant data were obtained by analyzing the gene expression database. The prognostic value of TCF19 was determined by analyzing various clinical parameters, such as survival duration, age, the stage of the tumor, and sex of the patients. The single-sample gene set enrichment analysis method was used to determine the activity of TCF19 and the method was also used to assess the differences between the TCF19 transcriptome and protein levels. The correlation between TCF19 and various immune processes and elements such as immunosuppressants, stimulants, and major histocompatibility complexes were analyzed to gain insights into the role of TCF19. The coherent paths associated with the process of TCF19 signal transduction and the influence of TCF19 on immunotherapy biomarkers have also been discussed herein. Finally, three independent immunotherapy methods were used to understand the relationship between TCF19 and immunotherapy response. Results: It was observed that TCF19 was not significantly influenced by the age (5/33), sex (3/33), or tumor stage (3/21) of cancer patients. But the results revealed that TCF19 exhibited a potential prognostic value and could predict the survival rate of the patients. In some cases of this study, the activity and expression of TCF19 were taken at the same level (7/33). Conclusion: TCF19 is strongly related to immune cell infiltration, immunomodulators, and immunotherapy markers. Our study demonstrated that high expression levels of TCF19 are strongly linked with the immune-related pathways. Nevertheless, it is noteworthy that TCF19 is not significantly associated with immunotherapy response.

Ferroptosis-related long non-coding RNA signature predicts the prognosis of bladder cancer.

BACKGROUND: Ferroptosis is an iron-dependent programmed cell death modality that may have a tumor-suppressive function. Therefore, regulating ferroptosis in tumor cells could serve as a novel therapeutic approach. This article focuses on ferroptosis-associated long non-coding RNAs (lncRNAs) and their potential application as a prognostic predictor for bladder cancer (BCa). METHODS: We retrieved BCa-related transcriptome information and clinical information from the TCGA database and ferroptosis-related gene sets from the FerrDb database. Least absolute shrinkage and selection operator regression (LASSO) and Cox regression models were used to identify and develop predictive models and validate the model accuracy. Finally, we explored the inter-regulatory relationships between ferroptosis-related genes and immune cell infiltration, immune checkpoints, and m6A methylation genes. RESULTS: Kaplan-Meier analyses screened 11 differentially expressed lncRNAs associated with poor BCa prognosis. The signature (AUC = 0.720) could be utilized to predict BCa prognosis. Additionally, GSEA revealed immune and tumor-related pathways in the low-risk group. TCGA showed that the p53 signaling pathway, ferroptosis, Kaposi sarcoma - associated herpesvirus infection, IL - 17 signaling pathway, MicroRNAs in cancer, TNF signaling pathway, PI3K - Akt signaling pathway and HIF - 1 signaling pathway were significantly different from those in the high-risk group. Immune checkpoints, such as PDCD-1 (PD-1), CTLA4, and LAG3, were differentially expressed between the two risk groups. m6A methylation-related genes were significantly differentially expressed between the two risk groups. CONCLUSION: A new ferroptosis-associated lncRNAs signature developed for predicting the prognosis of BCa patients will improve the treatment and management of BCa patients.

Solitary seminal vesicle metastasis from ileal adenocarcinoma presenting with hematospermia: A case report.

BACKGROUND: Although metastatic adenocarcinoma of the ileum is not uncommon, solitary metastasis to the seminal vesicle has not been reported. We report a patient with recurrent hematospermia diagnosed with metastasis to the seminal vesicle following ileal adenocarcinoma resection, his subsequent management and outcome. CASE SUMMARY: A 46-year-old man presented with recurrent episodes of painless hematospermia. This was not associated with any lower urinary tract symptoms. He had a past medical history of ileal tumor at the terminal ileum with solitary mesenteric lymph node metastasis on presentation, and underwent partial ileectomy and lymphadenectomy 4 years ago. Subsequent investigations included positron-emission tomography and computed tomography imaging confirmed the very unusual diagnosis of a solitary tumor at the left seminal vesicle. Laparoscopic left-sided vesiculectomy was carried out. Histological analysis with immunohistochemistry showed that CDX-2 was positive and CK7 was negative, and the appearance was consistent with the diagnosis of recurrent metastatic adenocarcinoma of his previously treated intestine primary. The patient had an uneventful post-operative recovery. He received adjuvant chemoradiotherapy following surgery. He remained asymptomatic until he developed multiple bone and pulmonary metastases one year after surgery. CONCLUSION: Clinicians should be aware of hematospermia as the first symptom of metastatic recurrence in patients with a history of ileal adenocarcinoma.

Successful endoscopic surgery for emphysematous pyelonephritis in a non-diabetic patient with autosomal dominant polycystic kidney disease: A case report.

BACKGROUND: Emphysema pyelonephritis (EPN) is a very dangerous type of urinary tract infection. It is a lethal disease that develops rapidly and causes the patient to deteriorate rapidly, and it can easily lead to systemic infections and even sepsis. The incidence is extremely low, and it is prevalent in patients with diabetes. We here report a case of EPN in a non-diabetic patient with autosomal dominant polycystic kidney disease (ADPKD). We share the diagnosis and treatment procedure for this extremely rare condition to make this disease easier to identify and address early. CASE SUMMARY: A 47-year-old woman presented to the emergency department of our hospital with a high fever and left back pain lasting 4 d. She had a history of autosomal dominant polycystic kidney and polycystic liver. She was diagnosed with left type I EPN and her vital signs deteriorated so quickly that she underwent an emergency operation in which a D-J tube was inserted into her left ureter on the second day after admission. Two months later, she underwent a second-stage flexible ureteroscopy and lithotripsy. Despite postoperative sepsis, she finally recovered after active symptomatic support treatment and effective anti-infective treatment. CONCLUSION: Although EPN is more likely to occur in diabetic patients, for non-diabetic patients with ADPKD and upper urinary tract obstruction, the disease also causes rapid deterioration. Early and accurate diagnosis and timely removal of the obstruction by invasive means may be able to save the damaged kidney and the patient's life.