Cytoskeleton-associated protein 2-like (CKAP2L), a cell cycle-related protein, is correlated to tumor progression in some tumors. But there were no pan-cancer studies on CKAP2L, and its role in cancer immunotherapy is also unclear. The expression levels, expression activity, genomic alterations, DNA methylation and functions of CKAP2L in various tumors, as well as the associations between CKAP2L expression and patient prognosis, chemotherapy sensitivity, and tumor immune microenvironment, were all analyzed in a comprehensive pan-cancer analysis of CKAP2L by various databases, analysis websites, and R software. The experiments were also conducted to verify the analysis results. In the majority of cancers, CKAP2L expression and activity were markedly elevated. Elevated CKAP2L expression led to poor prognostic outcomes in patients, and is an independent risk factor for most tumors. Elevated CKAP2L causes decreased sensitivity to chemotherapeutic agents. Knockdown of CKAP2L significantly inhibited the proliferation and metastasis capacity of the KIRC cell lines and resulted in cell cycle G2/M arrest. In addition, CKAP2L was closely related to immune subtypes, immune cell infiltration, immunomodulators and immunotherapy markers (TMB, MSI), patients with high CKAP2L expression were more sensitive to immunotherapy in the IMvigor210 cohort. The results indicate that CKAP2L is a pro-cancer gene that serves as a potential biomarker for predicting patient outcomes. By inducing cells to transition from the G2 phase to the M phase, CKAP2L may promote cell proliferation and metastasis. Furthermore, CKAP2L is closely related to the tumor immune microenvironment and can be used as a biomarker to predict tumor immunotherapy.
Objectives Anoikis plays an active role in the metastasis and progression of many tumors and is emerging as a new target for tumor therapy. We aimed to develop an anoikis-related risk model to assess the prognosis of patients with bladder urothelial carcinoma (BLCA) and to explore its potential application value in immunotherapy. Methods Patient expression data and clinical data were obtained from GEO and TCGA database. Lasso regression was used to obtain a risk model and the clinical efficacy of risk model was evaluated with Cox regression, calibration curves, nomogram diagram, and receiver operating characteristics (ROC). Next, GSEA analysis was performed to estimate potential biological pathways for ARGS. The tumor microenvironment (TME) was also assessed, including cancer-associated fibroblast (CAF), CIBERSORT, XCELL, tumor immune exclusion, and tumor-associated macrophage (TAM). Then, ggpubr and ggplot2 packages were utilized to compare immune checkpoint expression discrepancies in different risk groups. Then, we also discussed the survival relevance of ARGS combined with immune checkpoints using survival and survminer packages and evaluated the sensitivity of immunotherapy for ARGS through the cancer immunome atlas (TCIA) and IMvigor210 cohort. Results 15 anoikis genes were identified to construct prognostic ARGS. ARGS can effectively divide BLCA cases into 2 groups with different clinical outcomes and reflect different TME. It was obvious that patients in the high-risk group could not benefit from immunotherapy. Conclusions ARGS can be used to stratify hazards and predict prognosis events in patients with BLCA and give remarkable guidance for personalized and precise immunotherapy.
BackgroundCHMP4C is one of the charged multivesicular protein (CHMP), and is involved in the composition of the endosomal sorting complex required for transport III (ESCRT-III), facilitating the necessary separation of daughter cells. CHMP4C has been proposed to be involved in the progression of different carcinomas. However, the value of CHMP4C in prostate cancer has not yet been explored. Prostate cancer is the most frequently occurring malignancy among male and remains a leading cause of deaths in cancers. So far, clinical therapy of prostate cancer is more inclined to molecular classification and specific clinical treatment and research. Our study investigated the expression and clinical prognosis of CHMP4C and explored its potential regulatory mechanism in prostate cancer. The immune status of CHMP4C in prostate cancer and relative immunotherapy were then analyzed in our study. Based on CHMP4C expression, a new subtype of prostate cancer was established for precision treatment.MethodsWe studied the expression of CHMP4C and relative clinical outcome using the online databases TIMER, GEPIA2, UALCAN, and multiple R packages. Meanwhile, the biological function, immune microenvironment and immunotherapy value of CHMP4C in prostate cancer were further explored on the R software platform with different R packages. Then we performed qRT-PCR, Western Blotting, transwell, CCK8, wound healing assay, colony formation assay and immunohistochemistry to verify the expression of CHMP4C, carcinogenesis and potential regulatory mechanisms in prostate cancer.ResultsWe found that the expression of CHMP4C is significant in prostate cancer and the high expression of CHMP4C represents a poor clinical prognosis and malignant progression of prostate cancer. In subsequent vitro validation, CHMP4C promoted the malignant biological behavior of prostate cancer cell lines by adjusting the cell cycle. Based on CHMP4C expression, we established two new subtypes of prostate cancer and found that low CHMP4C expression has a better immune response while high CHMP4C expression was more sensitive to paclitaxel and 5-fluorouracil. Above findings revealed a new diagnostic marker for prostate cancer and facilitated the subsequent precise treatment of prostate cancer.
Purpose: Establishment of Sister Chromatid Cohesion N-Acetyltransferase 2 (ESCO2) is a member of histone acetyltransferases. ESCO2 is involved in the mitotic S-phase adhesins acetylation and is responsible for bridging two sister chromatids. However, present ESCO2 cancer research is limited to a few cancers. No systematic pan-cancer analysis has been conducted to investigate its role in diagnosis, prognosis, and effector function. Methods:We thoroughly examined the ESCO2 carcinogenesis in pan-cancer by combining public databases such as The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression Project (GTEx), cBioPortal, Human Protein Atlas (HPA), UALCAN, Xena Shiny databases, and TISCH. The analysis includes differential expression analysis, survival analysis, cellular effector function, gene mutation, single cell analysis, and tumor immune cell infiltration. Furthermore, we confirmed ESCO2's impacts on ccRCC cells' proliferative and invasive capacities in vitro. Results: In our study, ESCO2 is overexpressed in most cancers and has prognostic, predictive ability in various cancers. Moreover, ESCO2 expression positively correlates with tumor stage, grade, and tumor metastasis in several cancers. Function analysis revealed that ESCO2 participates in mitosis, cell cycle, DNA damage repair, and other processes. CDK1 was identified as a downstream gene regulated by ESCO2. Furthermore, ESCO2 might also be implicated in immune cell infiltration. Finally, ESCO2'S knockdown significantly inhibited the A498 cells' proliferation, invasion, and migration. Conclusions: In conclusion, ESCO2 is a possible pan-cancer biomarker and oncogene that can reliably predict the prognosis of cancer patients. ESCO2 was also implicated in the cell cycle and proliferation regulation. In a nutshell, ESCO2 is a therapeutically viable and dependable target.
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