scholarly journals A Pan-Cancer Analysis of Clinical Prognosis and Immune Infiltration of CKS1B in Human Tumors

2021 ◽  
Vol 2021 ◽  
pp. 1-25
Author(s):  
Yan Jia ◽  
Quan Tian ◽  
Kaitai Yang ◽  
Yi Liu ◽  
Yanfeng Liu

Although more and more evidence supports CDC28 protein kinase subunit 1B (CKS1B) is involved significantly in the development of human cancers, most of the researches have focused on a single disease, and pan-cancer studies conducted from a holistic perspective of different tumor sources have not been reported yet. Here, for the first time, we investigated the potential oncogenic and prognostic role of CKS1B across 33 tumors based on public databases and further verified it in a small scale by RNA sequencing or quantitative real-time PCR. CKS1B was generally highly expressed in a majority of tumors and had a notable correlation with the prognosis of patients, but its prognostic significance in different tumors was not exactly the same. In addition, CKS1B expression was also closely related to the infiltration of cancer-associated fibroblasts in tumors such as breast invasive carcinoma, kidney chromophobe, lung adenocarcinoma, and tumor-infiltrating lymphocytes in tumors such as glioblastoma multiforme, bladder urothelial carcinoma, and brain lower grade glioma. Moreover, reduced CKS1B methylation was observed in certain tumors, for example, adrenocortical carcinoma. Cell cycle and kinase activity regulation and PI3K-Akt signaling pathway were found to be involved in the functional mechanism of CKS1B. In conclusion, our first pan-cancer analysis of CKS1B contributes to a better overall understanding of CKS1B and may provide a new target for future cancer therapy.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 673-673
Author(s):  
Amir Ishaq Khan ◽  
Caroline Stewart Jansen ◽  
Jennifer Wilkinson Carlisle ◽  
Kevin Richard Melnick ◽  
Kyu Seo Kim ◽  
...  

673 Background: Renal cell carcinoma (RCC) has been shown to be a genetically and morphologically heterogeneous cancer. As studies show the significance of tumor-infiltrating lymphocytes (TIL) in cancer, it is critical to examine how the phenotype of TILs manifests in RCC. Such analysis may help explain the role of the immune landscape in developing resistance and its contribution to the high treatment failure observed in immunotherapy for RCC. This study compares the immune phenotype of primary tumors, venous tumor thrombi (VTT), and metastases, as well as multiple sites within primary tumors, and investigates whether inter- and intra-tumoral immune heterogeneity is present in RCC. The association of TIL levels and clinical prognosis will also be assessed and compared with current RCC prognostic scores. Methods: Our cohort included 15 VTT and 6 metastases (3 adrenal, 2 bone, 1 liver) with 20 matched primary tumors, as well as 25 non-metastatic primary tumors. The RCC tissue was collected and digested into single cell suspensions. Suspensions were stained for TIL surface markers and processed using flow cytometry. The data was analyzed to capture %CD8+ and %CD4+ in total tumor. The %CD28+ and %PD1+ of CD8+ cells were measured to describe the co-stimulatory and co-inhibitory receptor expression, respectively. Clinical data was obtained to calculate the Mayo Stage, Size, Grade, and Necrosis (SSIGN) and UCLA Integrated Staging System (UISS) scores for each patient and to evaluate recurrence. Results: Immunologic concordance was observed in all measured parameters (%CD8+, %CD4+, %CD28+, and %PD1+) for primary tumors and VTT, for primary tumors and their metastases, and for different sites within 10 primary tumors. In our overall cohort, %CD8+ was found to be inversely associated with recurrence (p = 0.02). Furthermore, %CD8+ was not significantly associated with patient Mayo SSIGN and UISS scores. Conclusions: Despite the genetic and morphologic heterogeneity seen in RCC, immunologic concordance was observed for both inter- and intra-tumoral analysis. The association between %CD8+ and recurrence presents a novel and objective immune-based prognostic factor for RCC, independent of Mayo SSIGN and UISS scores.


2021 ◽  
Vol 104 (2) ◽  
pp. 003685042110109
Author(s):  
Haiwei Wang ◽  
Xinrui Wang ◽  
Liangpu Xu ◽  
Ji Zhang ◽  
Hua Cao

CD133 is a valuable prognostic marker in multiple types of cancer. However, the expression, methylation levels, and prognostic relevance of CD133 have not been evaluated in a pan-cancer perspective. The expression and methylation levels of CD133 across different types of cancer were determined using The Cancer Genome Atlas (TCGA) dataset. Univariate cox regression and Kaplan-Meier survival were used to determine the prognostic significance of CD133 expression and methylation. CD133 was highly expressed in papillary renal cell carcinoma (PRCC) or pancreatic adenocarcinoma (PAAD). Correspondingly, PAAD and PRCC had low CD133 methylation levels. Through pan-cancer perspective analysis, we found that CD133 high expression was a poor prognostic factor in lower grade glioma (LGG), while, CD133 high expression was a good prognostic factor in PRCC. Moreover, genes positively correlated with CD133 expression were associated with the poor clinical outcomes of LGG. In PRCC, genes negatively correlated with CD133 expression were correlated with the poor overall survival. Furthermore, CD133 expression levels were highly correlated with the CD133 methylation levels in LGG or PRCC. Correspondingly, CD133 hypermethylation was a good prognostic factor in LGG. On the contrary, CD133 hypomethylation was a good prognostic factor in PRCC. We also found that CD133 was highly expressed and hypomethylated in wild type IDH subgroup of LGG. CD133 was highly expressed and hypomethylated in low stages and type1 of PRCC. CD133 high expression and hypomethylation were bad prognostic factors in LGG, while, CD133 high expression and hypomethylation were good prognostic factors in PRCC.


2021 ◽  
Vol 32 ◽  
Author(s):  
Mengdi He ◽  
Yiying Wang ◽  
Guodong Zhang ◽  
Kankan Cao ◽  
Moran Yang ◽  
...  

2021 ◽  
Author(s):  
Hongjuan Niu ◽  
Peiqiong Chen ◽  
Lu Fan ◽  
Boyu Sun

Abstract Background: Increased evidence supports the relationship between chromobox protein homolog 3 (CBX3) and tumorigenesis of some cancers. However, the role of CBX3 in pan-cancers remains poorly defined. In the research, we aimed to investigate the prognostic value and the immunological functions of CBX3. Results: We explored the potential oncogenic roles of CBX3 in mRNA and protein levels based on the diverse databases, including the expression, the correlation with prognosis, tumor microenvironment (TME), DNA methylation, protein phosphorylation and enrichment analysis across all TCGA tumors. The results show that CBX3 is overexpressed in multiple cancers, and significant correlations exist between high expression and adverse prognosis in most tumor patients. We observed an enhanced phosphorylation level in uterine corpus endometrial carcinoma, colon cancer and lung adenocarcinoma. A distinct relationship was also found between CBX3 expression and TME, including immune infiltration of tumor-infiltrating lymphocytes (TILs) and cancer-associated fibroblasts (CAFs), immune score or matrix score, immune checkpoints. The correlative transcription factors and miRNAs of CBX3-binding hub genes were analyzed to investigate the molecular mechanism. Moreover, alcoholism and alteration of DNA cellular biology may be involved in the functional mechanisms of CBX3. Conclusion: The first pan-cancer study offers a relatively comprehensive cognition on the oncogenic roles of CBX3 as a prognostic and immunological marker in various malignant tumors.


2007 ◽  
Vol 25 (7) ◽  
pp. 869-875 ◽  
Author(s):  
Rebecca C. Taylor ◽  
Ami Patel ◽  
Katherine S. Panageas ◽  
Klaus J. Busam ◽  
Mary S. Brady

Purpose Tumor-infiltrating lymphocytes (TILs) are considered a manifestation of the host immune response to tumor, but the influence of TILs on outcome remains controversial. Studies evaluating the prognostic significance of TILs were published before routine examination of draining lymph nodes by sentinel lymph node (SLN) biopsy, the most important predictor of survival in patients with melanoma. The prognostic implications of TILs were re-evaluated in a large group of patients undergoing SLN biopsy at our institution. Patients and Methods All patients who underwent SLN mapping for primary cutaneous melanoma between January 1996 and July 2005 were evaluated. Univariate and multivariate analyses were performed to assess factors that predict SLN positivity and survival. Factors analyzed included Breslow thickness, ulceration, anatomic site, sex, Clark level, age, mitotic rate, and the presence (brisk or nonbrisk) or absence of TIL. Results Eight hundred eighty-seven patients underwent SLN mapping, and a SLN was identified in 875 patients (98.8%). The SLN was positive for tumor in 156 patients (17.6%). Multivariate analysis revealed that only Breslow thickness (P < .0001), ulceration (P = .0004), male sex (P = .03), and absent TILs (P = .0003) were independently predictive of the presence of SLN metastases. In melanomas with a brisk TIL infiltrate, the probability of a positive SLN was 3.9% as compared with 26.2% for melanomas in which TILs were absent. TILs were not an independent predictive factor for survival. Conclusion The absence of TILs, together with increasing Breslow thickness, presence of ulceration and male sex, predicts SLN metastasis in patients undergoing SLN biopsy for primary cutaneous melanoma.


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