ABSTRACT
Background: PLAC8 has been identified in the progression of various cancers by inducing tumorigenesis, immune response, chemotherapy resistance and metastasis. Nevertheless, the precise biological function of PLAC8 in renal cancer remains unknown. Methods: We obtained the expression profile and associated clinical characteristics of patients diagnosed with clear cell renal cell carcinoma (ccRCC) from The Cancer Genome Atlas database. The biological behavior of specific cell lines was detected using Cell Counting Kit-8 (CCK-8), colony formation, and 5-ethynyl-2'-deoxyuridine (EdU) assay. A prognostic model was constructed based on PLAC8-related molecules through a machine-learning algorithm. Results: We observed overexpression of PLAC8 in ccRCC patients. In addition, PLAC8 has been identified as being linked to unfavorable clinical characteristics and adverse prognosis outcomes. Biological enrichment analysis revealed the potential involvement of PLAC8 in cell cycle checkpoints, mitotic phase transformation, immunotherapy-predicted and reactive oxygen species (ROS) related pathways. In addition, immune analyses showed that PLAC8 was involved in remodeling the tumor microenvironment (TME) and affecting the effect of immunotherapy in ccRCC patients. In vitro experiments demonstrated a significant reduction in the proliferation, invasion and migration of renal cancer cells following the knockdown of PLAC8. Finally, LASSO logistics regression was applied to construct a prognosis model, which presented a favorable prediction ability on the prognosis of ccRCC. Conclusion: Our results implied that PLAC8 may be a novel immunotherapy biomarker of ccRCC, which is a crucial molecule in remodeling the cancer microenvironment. PLAC8 can predict immunotherapy response and is expected to guide precise treatment.
ABSTRACT
Background: Post-renal transplant patients have a high likelihood of developing renal cancer. However, the underlying biological mechanisms behind the development of renal cancer in post-kidney transplant patients remain to be elucidated. Therefore, this study aimed to investigate the underlying biological mechanism behind the development of renal cell carcinoma in post-renal transplant patients. Methods: Next-generation sequencing data and corresponding clinical information of patients with clear cell renal cell carcinoma (ccRCC) were obtained from The Cancer Genome Atlas Program (TCGA) database. The microarray data of kidney transplant patients with or without rejection response was obtained from the Gene Expression Omnibus (GEO) database. In addition, statistical analysis was conducted in R software. Results: We identified 55 upregulated genes in the transplant patients with rejection from the GEO datasets (GSE48581, GSE36059, and GSE98320). Furthermore, we conducted bioinformatics analyses, which showed that all of these genes were upregulated in ccRCC tissue. Moreover, a prognosis model was constructed based on four rejection-related genes, including PLAC8, CSTA, AIM2, and LYZ. The prognosis model showed excellent performance in prognosis prediction in a ccRCC cohort. In addition, the machine learning algorithms identified 19 rejection-related genes, including PLAC8, involved in ccRCC occurrence. Finally, the PLAC8 was selected for further research, including its clinical and biological role. Conclusion: In all, our study provides novel insight into the transition from the rejection of renal transplant to renal cancer. Meanwhile, PLAC8 could be a potential biomarker for ccRCC diagnosis and prognosis in post-kidney transplant patients.
ABSTRACT
Background: MicroRNA-497(miR-497) has been studied for its irreplaceable role of predicting the prognosis of various cancers, but there has been no systematic study to summarize the data. Consequently, we performed this meta-analysis to reveal the association between the expression level of miR-497 and cancer prognosis systematically. Materials and Methods: PubMed was searched for appropriate studies and a total of 12 eligible publications with 989 cancer patients were recruited into our analysis to assess the strength of the association. Hazard ratios (HRs) and odds ratios (ORs) were analyzed to finish this work. Results: The cancer patients who have high expressing level of miR-497 are less possible to have lymph node metastasis (OR = 0.25, 95% CI: 0.16-0.40, P < 0.001) and more likely to have favourable tumor-node-metastasis stage (OR = 0.29, 95% CI: 0.17-0.49, P < 0.001). Also, high miR-497 expression level was notably connected to better overall survival (pooled HR = 0.41, 95% CI: 0.32-0.53, P < 0.001). Conclusions: High expressing levels of miR-497 might be a potential biomarker which can be used to predict the better prognosis of different cancer types.
ABSTRACT
Tau, a microtubule-associated protein, has been investigated primarily in neurons. Recently, tau has been explored to be associated with increased drug resistance in various kinds of cancers. We found that the tau was expressed in prostate cancer cell lines DU145 and PC-3. We also reported that recurrent prostate cancer cells after docetaxel treatment have higher levels of microtubule-associated protein tau. In vitro, inactivation of tau by gene knockdown suppressed cell proliferation and sensitized docetaxel cytotoxicity. Also, our results demonstrated that the PI3K/Akt/mTOR pathway was upregulated in DU145 docetaxel-resistant cells compared with the DU145-naïve cells. Thus, targeting tau protein and PI3K/Akt/mTOR pathway are promising strategies to enhance docetaxel response for the treatment of prostate cancer.
ABSTRACT
IgG4-related inflammatory pseudotumors are lesions characterized by plasma cell-rich histologic pattern, abundant IgG4-positive plasma cells and high serum IgG4 levels. A 64-year-old man was admitted to our hospital for an ultrasound-documented space-occupying lesion of the left kidney. Renal tumor of the left kidney was suspected based upon results of computed tomography and nuclear magnetic resonance, and laparoscopic radical nephrectomy was conducted. The final diagnosis of IgG4-related inflammatory pseudotumor was made based on histopathological examination and IgG4 immunostaining. The patient received steroid therapy. To our knowledge, this is the first case of IgG4-related inflammatory pseudotumor of the kidney reported in China.
