Identification of docetaxel-related biomarkers for prostate cancer.

Prostate cancer (PCa) which was the second commonly diagnosed malignancy, contributed to the top fifth carcinoma death in men. Nevertheless, the main chemotherapeutic agent docetaxel came to failure due to chemoresistance. Recently, increasing evidence suggested the importance of tumour microenvironment (TME) in PCa. The present study aimed to explore the specific TME in PCa and find biomarkers related to both immune infiltration and docetaxel. The docetaxel-specific genes and differential expression genes comparing PCa with normal control samples were derived using DESeq2 and zinbwave with GSE140440, TCGA and GTEx datasets. Immune-infiltration-related genes were identified using CIBERSORT and co-expression network analysis. Key genes related to both docetaxel and immune infiltrating in PCa, including nine genes, namely ZNF486, IFI6, TMOD2, HSPA4L, ITPR1, LRRC37A7P, APOC1, APOBEC3G, and ITGA2, were determined by overlapping above three gene sets. ITGA2 was then defined as the hub gene for its significant prognostic implications. Further validations conducted on Oncomine, GEO, TISIDB, MSigDB, and The Human Protein Atlas confirmed the docetaxel-specific and immune infiltrating characteristics of ITGA2. To sum up, our findings could provide a better understanding of immune infiltrating and docetaxel-resistance in PCa, mostly, ITGA2 could serve as potential prognosis biomarkers and targets for the combination of docetaxel.

Pan-Cancer Analysis of the Prognostic and Immunotherapeutic Value of MITD1.

Microtubule-interacting and trafficking domain containing 1 (MITD1) is associated with abscission during cytokinesis. However, systematic investigation into its role in cancer is lacking. Therefore, we explored the pan-cancer role of MITD1 using multiple databases. Expression and clinical survival, immunological, and enrichment analyses were performed using R packages and online tools. For breast cancer, single-cell level analysis, immunochemistry, and in vitro experiments were performed to explore the mechanism of MITD1. A nomogram was established to predict the prognosis of patients with breast cancer and evaluate the immunotherapy biomarker based on two datasets. In some cancers, high MITD1 expression was associated with a more favorable prognosis. For instance, it inhibited tumor cell proliferation and migration in breast cancer. MITD1 may regulate cancer development by altering the tumor microenvironment, and MITD1 expression may predict the response to immune checkpoint blockade, platinum, and poly ADP-ribose polymerase inhibitor therapies. Our nomogram was used to determine the prognosis of patients with breast cancer. MITD1 can also predict the response to immunotherapy. Our first pan-cancer study of MITD1 has shown that it plays different roles in cancer development and therapy. In breast cancer, MITD1 inhibited cell proliferation and migration and serves as a new biomarker.

Key sunitinib-related biomarkers for renal cell carcinoma.

BACKGROUND: Renal cell carcinoma (RCC) contributed to 403,262 new cases worldwide in 2018, which constitutes 2.2% of global cancer, nevertheless, sunitinib, one of the major targeted therapeutic agent for RCC, often developed invalid due to resistance. Emerging evidences suggested sunitinib can impact tumor environment which has been proven to be a vital factor for tumor progression. METHODS: In the present study, we used ssGSEA to extract the immune infiltrating abundance of clear cell RCC (ccRCC) and normal control samples from GSE65615, TCGA, and GTEx; key immune cells were determined by Student's t-test and univariable Cox analysis. Co-expression network combined with differentially expressed analysis was then applied to derive key immune-related genes for ccRCC, followed by the identification of hub genes using differential expression analysis. Subsequently, explorations and validations of the biological function and the immune-related and sunitinib-related characteristics were conducted in KEGG, TISIDB, Oncomine, ICGC, and GEO databases. RESULTS: We refined immature dendritic cells and central memory CD4 T cells which showed associations with sunitinib and ccRCC. Following, five hub genes (CRYBB1, RIMBP3C, CEACAM4, HAMP, and LYL1) were identified for their strong relationships with sunitinib and immune infiltration in ccRCC. Further validations in external data refined CRYBB1, CEACAM4, and HAMP which play a vital role in sunitinib resistance, immune infiltrations in ccRCC, and the development and progression of ccRCC. In conclusion, our findings could shed light on the resistance of sunitinib in ccRCC and provide novel biomarkers or drug targets for ccRCC.

Benefits from standalone durvalumab treatment in an elderly patient with advanced prostatic sarcoma: a case report.

There is a lacking of effective therapeutic strategies in the treatment of advanced prostatic sarcoma with high-frequency microsatellite instability (MSI-H) or mismatch repair deficient (dMMR). In this study, we present the first described a case of advanced MSI-H and dMMR prostatic sarcoma in elderly patients with multiple comorbidities, who received an anti-PD-L1 monoclonal antibody (durvalumab) as the first-line treatment and achieved partial remission (PR) without visible adverse events. A 91-year-old male patient presented with frequent urination and defecation difficulty for over three months, aggravating for ten days. Digital rectal examination showed the prostate gland was III° enlargement and tough with a smooth surface. The MRI showed occupying lesions in the prostate without distant metastasis. Then, the prostate biopsy showed poorly differentiated small round cell malignant tumor and considered prostatic sarcoma. Immunohistochemistry showed MSI-H and dMMR prostatic sarcoma. Durvalumab alone was applied at a cycle of every 21 days (500 mg/day) for 18 months and achieved PR two months since the treatment. During the treatment, we didn't observe rash, immune-related pneumonia, hepatitis, and other adverse events. Also, no recurrence or metastasis was observed until now. Durvalumab is effective and safe in the treatment of advanced MSI-H or dMMR prostatic sarcoma in an elderly patient. It is promising to be an available choice for advanced prostate sarcoma, which is unsuitable for surgery, conventional chemotherapy, and radiotherapy.

A comprehensive characterization of the transcriptome in enzalutamide resistance prostate cancer.

BACKGROUND: Prostate cancer (PCa) contributes to more than 1.2 million newly diagnosed cases and more than 350,000 deaths each year, making it the second most common malignancy and the fifth leading cause of cancer-related deaths in men worldwide. Treatment of PCa is further complicated by drug resistance to enzalutamide. The present study comprehensively details the genomic characteristics of enzalutamide-resistant PCa. METHODS: The determination of enzalutamide-related genes in GSE163240 and GSE136129 was conducted by differential expression analysis, gene set enrichment analysis (GSEA) suggested that these genes were highly correlated with immune-related pathways. Subsequently, network analysis including module analysis and degree analysis and univariable cox analysis were conducted, which led to the identification of both hub genes [contactin 2 (CNTN2) and frizzled class receptor 2 (FZD2)]. RESULTS: GSEA suggested that these genes were highly correlated with immune-related pathways. Subsequently, network analysis, including module analysis and degree analysis, and univariable Cox analysis resulted in the identification of two hub genes, CNTN2 and FZD2, which were further validated using the Gene Expression Omnibus (GEO) and Molecular Signatures Database (MSigDB). GSEA and CIBERSORT indicated that both hub genes were highly correlated with immune-related functions in PCa. CONCLUSIONS: In conclusion, this study comprehensively described the transcriptome landscape of enzalutamide-resistant PCa and identified two hub genes, CNTN2 and FZD2, that play an important role in enzalutamide-mediated immune infiltration in PCa.

An Unusual Case of Metastatic Basal Cell Carcinoma of the Prostate: A Case Report and Literature Review.

Background: Primary basal cell carcinoma (BCC) is a rare prostate cancer. Currently, a standard treatment regime for BCC of the prostate is lacking and most patients have a poor prognosis. We reported on a patient with BCC of the prostate whose cancer metastasized after undergoing a radical prostatectomy and whose prognosis improved after treatment with etoposide. Case Presentation: A 62-year-old male with a history of seminoma was admitted complaining of intermittent gross hematuria for 1 month. Following a prostate biopsy, the patient was diagnosed with BCC of the prostate and received radical prostatectomy and radiotherapy. Initially, the patient's symptoms improved; however, 2 years later, a chest computed tomography (CT) scan revealed lung nodules. The patient did not exhibit any symptoms of BCC of the prostate; however, pathological examination and immunohistochemical staining of the nodules confirmed metastatic BCC of the prostate. Chemotherapy with docetaxel and cisplatin was well-tolerated but did not slow disease progression. Next-generation sequencing revealed mutations in the ataxia telangiectasia-mutated (ATM), SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily b-member 1 (SMARCB1), and phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) genes. The patient did not receive targeted therapy owing to financial limitations and instead, etoposide was administered. A 9-month follow-up chest CT scan showed an 80% reduction in existing lung nodules and no new nodules had developed. Conclusion: Our patient, diagnosed with recurrent prostate BCC after receiving a radical prostatectomy, responded to treatment with etoposide. Radical prostatectomy and radiotherapy should remain first-line therapy; however, etoposide may be an alternative second-line therapy when other options are not available. Consensus regarding treatment plans, and the molecular mechanisms behind prostate BBC, must be elucidated.

Experimental Study of the Formation Rate and Distribution of Methane Hydrate in Layered Sand.

The geological structure and gas hydrate occurrence are stratification-dependent in the vertical direction. It is necessary to explore the formation processes and distribution characteristics of methane hydrate in layered porous media. The sand sample consists of two equal parts in a testing cylinder. The upper part is 0.5-1 mm sand in particle diameter, and the lower parts are 0.075∼0.5, 0.5∼1, and 1∼2 mm. The experimental results show that the formation rate of methane hydrate gradually decreases as the reaction goes on, and it is higher in layered sand than in nonlayered sand in the beginning. With the increase of the sand size in the lower part, saturation of methane hydrate gradually decreases in the upper part and increases in the lower part. In the layered sand, saturation of methane hydrate is higher in the sand layer whose particle size is bigger. The abovementioned results can be used to predict the favorable area where methane hydrate may appear in different stratigraphic structures in nature.