scholarly journals KIFC1 Is Associated with Basal Type, Cisplatin Resistance, PD-L1 Expression and Poor Prognosis in Bladder Cancer

2021 ◽  
Vol 10 (21) ◽  
pp. 4837
Author(s):  
Yohei Sekino ◽  
Quoc Thang Pham ◽  
Kohei Kobatake ◽  
Hiroyuki Kitano ◽  
Kenichiro Ikeda ◽  
...  

Kinesin family member C1 (KIFC1), a minus end-directed motor protein, is reported to play an essential role in cancer. This study aimed to analyze KIFC1 expression and examine KIFC1 involvement in cisplatin resistance in bladder cancer (BC). Immunohistochemistry showed that 37 of 78 (47.4%) BC cases were positive for KIFC1. KIFC1-positive cases were associated with high T stage and lymph node metastasis. Kaplan-Meier analysis showed that KIFC1-positive cases were associated with poor prognosis, consistent with the results from public databases. Molecular classification in several public databases indicated that KIFC1 expression was increased in basal type BC. Immunohistochemistry showed that KIFC1-positive cases were associated with basal markers 34βE12, CK5 and CD44. KIFC1 expression was increased in altered TP53 compared to that in wild-type TP53. Immunohistochemistry showed that KIFC1-positive cases were associated with p53-positive cases. P53 knockout by CRISPR-Cas9 induced KIFC1 expression in BC cell lines. Knockdown of KIFC1 by siRNA increased the sensitivity to cisplatin in BC cells. Kaplan-Meier analysis indicated that prognosis was poor among KIFC1-positive BC patients treated with cisplatin-based chemotherapy. Immunohistochemistry showed that KIFC1-positive cases were associated with PD-L1-positive cases. High KIFC1 expression was associated with a favorable prognosis in patients treated with atezolizumab from the IMvigor 210 study. These results suggest that KIFC1 might be a promising biomarker and therapeutic target in BC.

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Shan Liang ◽  
Zhulin Yang ◽  
Daiqiang Li ◽  
Xiongying Miao ◽  
Leping Yang ◽  
...  

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant disease, but the genetic basis of PDAC is still unclear. In this study, Nectin-2 and DDX3 expression in 106 PDAC, 35 peritumoral tissues, 55 benign pancreatic lesions, and 13 normal pancreatic tissues were measured by immunohistochemical methods. Results showed that the percentage of positive Nectin-2 and DDX3 expression was significantly higher in PDAC tumors than in peritumoral tissues, benign pancreatic tissues, and normal pancreatic tissues (P<0.01). The percentage of cases with positive Nectin-2 and DDX3 expression was significantly lower in PDAC patients without lymph node metastasis and invasion and having TNM stage I/II disease than in patients with lymph node metastasis, invasion, and TNM stage III/IV disease (P<0.05orP<0.01). Positive DDX3 expression is associated with poor differentiation of PDAC. Kaplan-Meier survival analysis showed that positive Nectin-2 and DDX3 expression were significantly associated with survival in PDAC patients (P<0.001). Cox multivariate analysis revealed that positive Nectin-2 and DDX3 expression were independent poor prognosis factors in PDAC patients. In conclusion, positive Nectin-2 and DDX3 expression are associated with the progression and poor prognosis in PDAC patients.


2021 ◽  
Author(s):  
Zhiqiang Yao ◽  
Jiajia Zhang ◽  
Chaohu Chen ◽  
Pan Li ◽  
Jinlong Cao ◽  
...  

Abstract Background: Bladder cancer (BLCA) is the most common malignancy of urinary system with a high recurrence rate. We aimed to explore the relationship between cathepsin V (CTSV) expression and prognosis in patients with bladder cancer.Methods: The RNA-Seq gene expression data and corresponding clinical information with BLCA were downloaded from TCGA database. The gene expression profiles of GSE13507 and GSE133624 were downloaded from GEO database. BLCA patients were divided into high and low expression group according to the cutoff value of CTSV expression. The relationship between clinicopathologic characteristics and CTSV expression was analyzed with the Wilcoxon signed-rank test and logistic regression. Kaplan-Meier analysis and Cox regression were used to analyze the relationship between overall survival and clinicopathologic characteristics. Gene set enrichment analysis (GSEA) was utilized to identify enriched KEGG pathway.Results: High expression of CTSV was significantly correlated with pathological grade (OR = 1.662 for low vs. high), clinical stage (OR = 1.589 for I-II vs. III-IV), status (OR = 1.435 for normal vs. tumor), T stage (OR = 1.589 for T1-2 vs. T3-4), and M stage (OR = 4.499 for M0 vs M1). The expression of CTSV was significantly increased in BLCA compared with normal tissue (P < 0.001). Kaplan-Meier survival analysis showed that BLCA patients with high expression of CTSV had a poorer prognosis than low expression of CTSV patients (P = 0.0016). Univariate Cox analysis showed that high expression of CTSV was significantly associated with poorer overall survival (HR:1.662, 95%CI:1.209-2.286, P = 0.002). Multivariate Cox regression showed that high expression of CTSV was an independent risk factor for poor prognosis in BLCA patients (HR: 1.495, 95%CI: 1.069-2.089, P = 0.019). We also used the GSE13507 and GSE133624 to verify whether CTSV was differently expressed in bladder cancer tissues and normal tissues. The results showed that CTSV expression was significantly increased in BLCA patients (P < 0.05). Finally, GSEA was used to show 22 enriched signaling pathways in a high phenotype.Conclusion: High expression of CTSV in bladder cancer is associated with poor prognosis and may serve as a new biomarker. In addition, the chemokine signaling pathway, MAPK signaling pathway, Wnt signaling pathway, JAK-STAT signaling pathway, tight Junction and cell adhesion molecules may be the key pathway regulated by CTSV in BLCA.


2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Qi Zhang ◽  
Junxiu Wu ◽  
Xinpeng Chen ◽  
Ming Zhao ◽  
Dahong Zhang ◽  
...  

Objective. This work analyzes the role of versican (VCAN) on bladder cancer (BLCA). Versican (VCAN) is a chondroitin sulfate proteoglycan which is important for tumorigenesis and the development of cancer. However, the expression of VCAN on human bladder cancer (BLCA) has been rarely reported. Methods. The clinical significance of VCAN in BLCA has been determined by our bioinformatics tools. Then, we performed immunohistochemical staining (IHC) and analyzed the correlation between VCAN expression and clinicopathological features. Results. The bioinformatics results reveal that a high VCAN mRNA level was significantly associated with stage, histological subtype, molecular subtype, and metastasis in BLCA. Furthermore, IHC reveals that expression of VCAN was significantly correlated with the number of tumors, invasion depth, lymph node metastasis, distant metastasis, and histological grade. Kaplan-Meier survival analysis reveals that patients with a high expression of VCAN have poor prognosis than those patients with a low expression of VCAN. According to our result from the bioinformatics database, the mechanism of VCAN in BLCA revealed that VCAN was related to FBN1 and genes of the ECM remodeling pathway (MMP1, MMP2). Conclusion. VCAN expression might be included in the process of carcinogenesis and prognosis. Hence, VCAN could be a reliable biomarker of the clinical prognosis on BLCA.


BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Nada Albarakati ◽  
Dareen Khayyat ◽  
Asharf Dallol ◽  
Jaudah Al-Maghrabi ◽  
Taoufik Nedjadi

Abstract Background The glutathione S-transferases (GSTs) are a superfamily of phase II detoxifying enzymes that inactivates a wide variety of potential carcinogens through glutathione conjugation. Polymorphic changes in the GST genes have been reported to be associated with increased susceptibility to cancer development and anticancer drug resistance. In this study, we investigated the association between genetic variants in GSTM1 and GSTP1 and patients’ clinicopathological parameters. The prognostic values of such associations were evaluated among bladder cancer patients. Methods Genotyping of GSTM1 and GSTP1 in bladder cancer patients was assessed using polymerase chain reaction followed by DNA sequencing. Overall survival was estimated using the Kaplan-Meier method and multiple logistic regression and correlation analysis were performed. Results The GSTM1 null genotype was significantly associated with poor overall survival compared with the wild-type GSTM1 genotype. There was a trend towards better overall survival in patients with wild-type GSTP1 allele (AA) compared with GSTP1 (AG/GG) genotype. Interestingly, Kaplan-meier survival curve for GSTM1 null patients adjusted for sub-cohort with amplified HER2 gene showed poor survival compared with the GSTM1 null/ non-amplified HER2 gene. Also the same population when adjusted with HER2 protein expression, data showed poor survival for patients harboring GSTM1 null/high HER2 protein expression compared with low protein expression. Conclusion This study focuses on the impact of GSTM1 null genotype on bladder cancer patients’ outcome. Further investigations are required to delineate the underlying mechanisms of combined GSTM−/− and HER2 status in bladder cancer.


2020 ◽  
Author(s):  
Keqian Zhang ◽  
Tianqi Mao ◽  
Zhicheng He ◽  
Xiaojiao Wu ◽  
Yu Peng ◽  
...  

Abstract Background: Breast cancer is one of the most common cancers among females with high morbidity and mortality. MicroRNAs (miRNAs) have been reported to play important roles in the development of cancers. However, the prognostic value of microRNA-421 (miR-421) in breast cancer have not been extensively explored.Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the relative expression of miR-421 in breast cancer tissue samples. Relationships between miR-421 expression and clinicopathological factors were analyzed by chi-square test. The effects of several variables on survival status were tested by Kaplan-Meier curve and Cox proportional hazards regression analyses.Results: MiR-421 expression was significantly decreased in breast cancer tissues, compared with adjacent noncancerous tissues (P<0.001). Moreover, abnormal miR-421 expression was closely correlated with lymph node metastasis (P<0.001), TNM stage (P=0.021), and differentiation (P=0.044) of breast cancer patients. Kaplan-Meier analysis revealed that patients with low miR-421 expression had a shorter overall survival time than those with high miR-421 expression (P=0.001). Furthermore, multivariate analysis demonstrated that miR-421 (P=0.014, HR=2.000, 95%CI: 1.149-3.480) was an independent prognostic indicator in breast cancer patients, as well as lymph node metastasis (P=0.016, HR=1.987, 95%CI: 1.137-3.474).Conclusion: The reduced expression of miR-421 may predict the poor prognosis of breast cancer and miR-421 may be involved in the progression of breast cancer.


2018 ◽  
Vol 97 (7) ◽  
pp. 787-794 ◽  
Author(s):  
L.-L. Yang ◽  
L. Wu ◽  
G.-T. Yu ◽  
W.-F. Zhang ◽  
B. Liu ◽  
...  

Targeted therapy using monoclonal antibodies (mAbs) has emerged as a widely used form of immunotherapy in head and neck squamous cell carcinoma (HNSCC). Membrane-associated glycoprotein CD317 has been preferentially overexpressed by multiple myeloma cells, and its humanized mAb has been previously used in clinical trials. However, overexpression of CD317 in HNSCC and its correlation with tumor immunity is still uncertain. Here, the immunoreactivity of CD317 was detected in human HNSCC tissue microarrays, which contained 43 oral mucosa samples, 48 dysplasia samples, and 165 primary HNSCC. We found that CD317 expression was up-regulated in HNSCC tumor cells, and the CD317 expression level was independent of the histological grade, tumor size, and lymph node metastasis. Moreover, Kaplan–Meier survival curve analysis showed that patients with high expression of CD317 had a poor prognosis compared with patients with low expression. Furthermore, CD317 overexpression in HNSCC was correlated with immune checkpoint molecules PD-L1, B7-H3, and B7-H4 and tumor-associated macrophage markers (CD68 and CD163). We also observed that CD317 was overexpressed in immunocompetent mouse HNSCC tissue compared with normal tissue. Taken together, our findings demonstrate that CD317 overexpression indicates poor prognosis and is correlated with immune-related components in this patient cohort. CD317 may serve as a potential target for effective immunotherapy of HNSCC.


2013 ◽  
Vol 35 ◽  
pp. 163-172 ◽  
Author(s):  
Zhu-lin Yang ◽  
Leping Yang ◽  
Qiong Zou ◽  
Yuan Yuan ◽  
Jinghe Li ◽  
...  

Background. Gallbladder cancers (GBCs) are highly aggressive cancers with high mortality. However, biological markers for the progression and prognosis of GBC are currently unavailable in the clinic.Objective. To identify biomarkers for predicting GBC metastasis and prognosis.Methods. We examined ALDH1A3 and GPX3 expressions in 46 squamous cell/adenosquamous carcinomas (SC/ASC) and 80 adenocarcinomas (AC) by using immunohistochemistry.Results. Positive ALDH1A3 and negative GPX3 expressions were significantly associated with lymph node metastasis and invasion of SC/ASCs and ACs. Univariate Kaplan-Meier analysis showed that either positive ALDH1A3(P<0.001)or negative GPX3(P<0.001)expression significantly correlated with decreased overall survival in both SC/ASC and AC patients. Multivariate Cox regression analysis showed that positive ALDH1A3 expression or negative GPX3 expression was an independent poor-prognostic predictor in both SC/ASC and AC patients.Conclusions. Our study suggested that positive ALDH1A3 and negative GPX3 expressions are closely associated with clinical pathological behaviors and poor prognosis of gallbladder cancer.


2021 ◽  
Vol 11 ◽  
Author(s):  
Jiaxing Lin ◽  
Xiao Xu ◽  
Tianren Li ◽  
Jihang Yao ◽  
Meng Yu ◽  
...  

BackgroundBladder cancer lacks useful and robust prognostic markers to stratify patients at risk. Our study is to identify a robust prognostic marker for bladder cancer.MethodsThe transcriptome and clinical data of bladder cancer were downloaded from multiple databases. We searched for genes with robust prognosis by Kaplan-Meier analysis of the whole genome. CIBERSORT and TIMER algorithm was used to calculate the degree of immune cell infiltration.ResultsWe identified OLFML2B as a robust prognostic marker for bladder cancer in five cohorts. Kaplan-Meier analysis showed that patients with a high level of OLFML2B expression had a poor prognosis. The expression of OLFML2B increased with the increase of stage and grade. We found that patients with high expression of OLFML2B still had a poor prognosis in two small bladder cancer cohorts. OLFML2B also has the prognostic ability in ten other tumors, and the prognosis is poor in high expression. The correlation analysis between OLFML2B and immune cells showed that it was positively correlated with the degree of macrophage infiltration and highly co-expressed with tumor-associated macrophage markers. Finally, the Wound-healing assay and Colony formation assay results showed that the migration and proliferation ability of bladder cancer cell lines decreased after the knockdown of OLFML2B.ConclusionsIn summary, OLFML2B is a robust risk prognostic marker, and it can help patients with bladder cancer improve individualized treatment.


Sign in / Sign up

Export Citation Format

Share Document