scholarly journals Prognostic Significance of KIF11 and KIF14 Expression in Pancreatic Adenocarcinoma

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3017
Author(s):  
Anna Klimaszewska-Wiśniewska ◽  
Izabela Neska-Długosz ◽  
Karolina Buchholz ◽  
Justyna Durślewicz ◽  
Dariusz Grzanka ◽  
...  

Available biomarkers for pancreatic adenocarcinoma (PAC) are inadequate to guide individual patient prognosis or therapy. Therefore, herein we aimed to verify the hypothesis that differences in the expression of KIF11 and KIF14, i.e., molecular motor proteins being primarily implicated in cell division events could account for the differences in the clinical outcome of PAC patients. In-house immunohistochemistry was used to evaluate the protein expressions of KIF11 and KIF14 in PAC, whereas RNA-seq datasets providing transcript expression data were obtained from public sources. IHC and mRNA results were correlated with clinicopathological features and overall survival (OS). Furthermore, the genes co-expressed with KIF11 or KIF14 were predicted and functionally annotated. In our series, malignant ducts displayed more intense but less abundant KIF11 staining than normal-appearing ducts. The former was also true for KIF14, whereas the prevalence of positive staining was similar in tumor and normal adjacent tissues. Based on categorical immunoreactive scores, we found KIF11 and KIF14 to be frequently downregulated or upregulated in PAC cases, respectively, and those with elevated levels of either protein, or both together, were associated with better prognosis. Specifically, we provide the first evidence that KIF11 or KIF14 proteins can robustly discriminate between patients with better and worse OS, independently of other relevant clinical risk factors. In turn, mRNA levels of KIF11 and KIF14 were markedly elevated in tumor tissues compared to normal tissues, and this coincided with adverse prognosis, even after adjusting for multiple confounders. Tumors with low predicted KIF11 or KIF14 expression were seen to have enrichment for circadian clock, whereas those with high levels were enriched for the genomic instability-related gene set. KIF11 and KIF14 were strongly correlated with one another, and CEP55, ASPM, and GAMT were identified as the main hub genes. Importantly, the combined expression of these five genes emerged as the most powerful independent prognostic indicator associated with poor survival outcome compared to classical clinicopathological factors and any marker alone. In conclusion, our study identifies novel prognostic biomarkers for PAC, which await validation.

2021 ◽  
Vol 12 ◽  
Author(s):  
Jun Liu ◽  
Yi Lu ◽  
Wenan Huang ◽  
Zhibo He

Inhibitors of apoptosis proteins (IAPs) have been associated with tumor development and progression by affecting apoptosis through cell death signaling pathways. To date, eight IAPs (BIRC1–8) have been identified in mammalian cells. However, the role of IAPs in non–small cell lung cancer (NSCLC) development and progression has not been explored in depth. In this study, we used public datasets and bioinformatics tools to compare the expression, prognostic significance, and function of IAPs in NSCLC and its subtypes. Expression of IAPs in cancer and normal tissues and at different stages of NSCLC was compared with gene expression profiling interactive analysis, and their prognostic significance was analyzed with the Kaplan–Meier Plotter database. The correlations among IAPs were analyzed with the STRING database and SPSS19.0. Functional annotation of IAPs was analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment on the basis of the DAVID tool. Among patients with lung adenocarcinoma (LUAD), the expression level of BIRC5 was higher than that in normal samples, and the expression of BIRC1 and BIRC5 significantly varied in different stages. Moreover, the BIRC1–3 and BIRC5 mRNA levels were associated with overall survival (OS), and the BIRC1–2 and BIRC5–6 mRNA levels were associated with progression-free survival (PFS). Among patients with lung squamous cell carcinoma (LUSC), the expression level of BIRC1 was lower and that of BIRC5 was higher than those in normal tissues, and BIRC5 expression significantly varied in different stages. BIRC1 expression was associated with OS, whereas BIRC2 and BIRC6 expression was associated with PFS. Enrichment analysis showed that most IAPs are associated with ubiquitin- and apoptosis-related pathways. Collectively, this study suggests BIRC5 as a potential diagnostic and staging marker, BIRC1 as a potential marker of OS, and BIRC2 and BIRC6 as potential PFS markers for patients with NSCLC. These highlight new targets for the early detection, treatment, and management of NSCLC.


2018 ◽  
Vol 36 (2) ◽  
pp. 137-143 ◽  
Author(s):  
Hiroaki Saito ◽  
Yusuke Kono ◽  
Yuki Murakami ◽  
Yuji Shishido ◽  
Hirohiko Kuroda ◽  
...  

Background: Although preoperative lymphopenia is reportedly a prognostic factor in cancer patients, the association between postoperative lymphopenia and patient prognosis has not been widely studied. Methods: We enrolled 352 patients who underwent surgery for gastric cancer (GC) between January 2005 and April 2013 to analyze correlations among pre- and postoperative lymphocyte counts (LCs) and prognosis in GC patients. Results: Pre- and postoperative (obtained 1 day after surgery) LCs were significantly correlated (r = 0.496, p < 0.0001). Pre- and postoperative LCs of elderly patients were significantly lower than those of non-elderly patients. Postoperative lymphocyte count was significantly lower in patients with a differentiated tumor than in those with an undifferentiated tumor. Based on the results of receiver operating characteristic analysis, patients were classified into subgroups as: preoperative LC ≥1,676 (pre-LCHigh), preoperative LC <1,676 (pre-LCLow); and as postoperative LC ≥855 (post-LCHigh), and postoperative LC <855 (post-LCLow). Five-year overall survival rates significantly differed between pre-LCHigh (82.5%) and pre-LCLow (71.6%) groups (p = 0.023); and also between the post-LCHigh (81.5%) and post-LCLow (69.5%) groups (p = 0.0072). The 5-year disease specific survival rates were 91.3 and 82.4% in patients with post-LCHigh and those with post-LCLow, respectively, and differences were statistically significant (p = 0.015). Multivariate analysis indicated that postoperative lymphocyte count was an independent prognostic indicator, along with age, gender, tumor size, lymph node metastasis, and venous invasion. Conclusions: Postoperative lymphocyte count is a useful predictive factor for prognosis in GC patients.


2018 ◽  
Vol 38 (5) ◽  
Author(s):  
Yan-Wu Zhou ◽  
Rong Li ◽  
Chao-Jun Duan ◽  
Yang Gao ◽  
Yuan-Da Cheng ◽  
...  

Chromosome 14 ORF 166 (C14orf166), a protein involved in the regulation of RNA transcription and translation, has been reported to possess the potency to promote tumorigenesis; however, the role of C14orf166 in non-small-cell lung cancer (NSCLC) remains unknown. The purpose of the present study was to assess C14orf166 expression and its clinical significance in NSCLC. Immunohistochemical staining, quantitative real-time PCR (qRT-PCR), and Western blotting were used to detect the C14orf166 protein and mRNA expression levels in NSCLC tissues compared with adjacent normal tissues, as well as in NSCLC cells lines compared with normal human bronchial epithelial cells (HBE). Then, the correlations between the C14orf166 expression levels and the clinicopathological features of NSCLC were analyzed. Additionally, the Cox proportional hazard model was used to evaluate the prognostic significance of C14orf166. We found that C14orf166 expression increased in carcinoma tissues compared with their adjacent normal tissues at the protein (P&lt;0.001) and mRNA levels (P&lt;0.001). High expression of C14orf166 was significantly associated with the T stage (P=0.006), lymph node metastasis (P=0.001), advanced TNM stage (P&lt;0.001), and chemotherapy (P&lt;0.001). Moreover, according to the survival analysis, patients with overexpressed C14orf166 were inclined to experience a shorter overall survival and disease-free survival time (P&lt;0.001). Multivariate COX analysis implied that C14orf166 was an independent prognostic biomarker. Taken together, our findings indicate that the overexpression of C14orf166 may contribute to the disease progression of NSCLC, represent a novel prognostic predictor and help high-risk patients make better decisions for subsequent therapy.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhiguo Liu ◽  
Hongyan Liu ◽  
Qian Dong ◽  
Hongyu Li ◽  
Bin Zhang ◽  
...  

Abstract Background The gasdermin E gene (GSDME, also known as DFNA5) is mutated in familial aging-related hearing loss. Recent studies have also revealed that the expression of DFNA5 is suppressed in many cancer types; however, little is known about the function of DFNA5 in head and neck squamous cell carcinoma (HNSCC). Accordingly, the aim of the present study was to evaluate the expression of DFNA5 and explore its prognostic value in HNSCC. Result We used a set of bioinformatics tools, including Oncomine, TIMER, TISIDB, cBioPortal, and GEPIA, to analyze the expression of DFNA5 in patients with HNSCC from public databases. Kaplan-Meier plotter was used to evaluate the potential prognostic significance of DFNA5. DFNA5 mRNA levels were significantly higher in HNSCC tissues than in normal tissues, and high DFNA5 expression was correlated with worse survival. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses showed that DFNA5 expression has a strong positive correlation with cell adhesion and the integrin signaling pathway, whereas its expression was negatively correlated with the levels of infiltrating B cells (cor = − 0.223, P = 8.57e-07) and CD8 T cells (cor = − 0.223, P = 2.99e-07). Conclusion This study demonstrates that DFNA5 expression has prognostic value for HNSCC patients. Moreover, these results suggest that regulation of lymphocyte infiltration is the mechanism underlying the function of DFNA5 in HNSCC.


2020 ◽  
Vol 40 (8) ◽  
Author(s):  
Limei Liu ◽  
Jiaomin Yang ◽  
Chao Wang

Abstract Background: Breast cancer (BC) is the most common malignancy in females and remains a main cause of cancer-associated death worldwide. The solute carrier (SLC) groups of membrane transport proteins, which control the influx of zinc, participate in ranging of physiological processes and may provide novel therapeutic targets of cancers. However, the prognostic values of individual SLC family 39 (SLC39A) genes in patients with BC are not clarified. Materials and Methods: The mRNA expression of SLC family 39 genes in BC was evaluated by using the UALCAN database. The prognostic values of overall survival (OS) of SLC family 39 genes in patients with BC were investigated by Kaplan–Meier plotter. The survival analysis of cells was determined by Project Achilles. Results: The analytic results suggested that SLC39A1, SLC39A3, SLC39A4, SLC39A5, SLC39A6, SLC39A7, SLC39A9, SLC39A10, SLC39A11 and SLC39A13 were significantly up-regulated in BC tissues compared with normal breast tissues. However, SLC39A8 and SLC39A14 were expressed higher in normal tissues than in BC tissues. High expression of SLC39A2, SLC39A3, SLC39A4, SLC39A5, SLC39A7, SLC39A12 and SLC39A13 was significantly associated with worse OS in patients with BC. In contrast, high mRNA levels of SLC39A6 and SLC39A14 indicated favorable OS. Through subgroup analysis, all abnormal expressed SLC family members were correlated with prognoses of patients with specific BC. Moreover, SLC39A7 was associated with proliferation and cloning of BC. Conclusions: Our results suggested that SLC family 39 members were promising prognostic biomarkers of BC. The SLC39A7 played a key role in growth and survival of BC cells.


2020 ◽  
Author(s):  
Zhiguo Liu ◽  
Hongyan Liu ◽  
Qian Dong ◽  
Hongyu Li ◽  
Bin Zhang ◽  
...  

Abstract The gasdermin E gene (GSDME, also known as DFNA5) is mutated in familial aging-related hearing loss. Recent studies have also revealed that the expression of DFNA5 is suppressed in many cancer types; however, little is known about the function of DFNA5 in head and neck squamous cell carcinoma (HNSCC). Accordingly, the aim of the present study was to evaluate the expression of DFNA5 and explore its prognostic value in HNSCC. We used a set of bioinformatics tools, including Oncomine, TIMER, TISIDB, cBioPortal, and GEPIA, to analyze the expression of DFNA5 in patients with HNSCC from public databases. Kaplan-Meier plotter was used to evaluate the potential prognostic significance of DFNA5. DFNA5 mRNA levels were significantly higher in HNSCC tissues than in normal tissues, and high DFNA5 expression was correlated with worse survival. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses showed that DFNA5 expression has a strong positive correlation with cell adhesion and the integrin signaling pathway, whereas its expression was negatively correlated with the levels of infiltrating B cells (cor = –0.223, P = 8.57e-07) and CD8 T cells (cor = –0.223, P = 2.99e-07). Overall, this study demonstrates that DFNA5 expression has prognostic value for HNSCC patients. Moreover, these results suggest that regulation of lymphocyte infiltration is the mechanism underlying the function of DFNA5 in HNSCC.


2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Feiyu Mao ◽  
Duguang Li ◽  
Zechang Xin ◽  
Yan Du ◽  
Xiaodong Wang ◽  
...  

COL17A1 (collagen type XVII alpha 1 chain) is known to be upregulated and has a prognostic role in many malignancies, as well as contributing to cell proliferation, apoptosis, and invasion. However, little knowledge is available on the expression and prognostic value of COL17A1 in pancreatic adenocarcinoma (PDAC). In our study, we searched the public database and found that mRNA and protein levels of COL17A1 are commonly upregulated in PDAC tissues. The immunohistochemical analysis conducted by us revealed enhanced expression of COL17A1 protein in 169 PDAC samples compared with that in 67 adjacent normal tissues. We also observed a significantly positive correlation between COL17A1 expression and lymph node metastasis ( p < 0.0001 ), TNM clinical stage ( p < 0.0001 ), and pathology differentiation ( p < 0.01 ). The KM-plot results indicated that PDAC patients with a high COL17A1 expression have a poorer overall survival ( p < 0.001 ) than those with a low COL17A1 expression. The result of the Cox regression analysis of multivariate data suggested COL17A1 is an independent prognostic indicator of PDAC patients’ overall survival. CCK-8, wound healing, and transwell assays suggested that COL17A1 knockdown markedly inhibited tumor proliferation and invasion in PDAC cells, and cells with COL17A1 overexpression had a prominently higher proliferative and invasive capacity. Knockdown of COL17A1 significantly upregulated the apoptosis rate. We deduce that upregulated COL17A1 activated the NF-κB pathway in PDAC cells. In summary, our studies showed the prognostic value of COL17A1 in PDAC and that COL17A1 may act as a molecular therapeutic target for PDAC treatment.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15047-e15047
Author(s):  
J. A. Posey ◽  
S. Koya ◽  
V. R. Katkoori ◽  
D. E. Davis ◽  
U. Manne

e15047 Introduction: Inactivation of the vitamin D receptor (VDR) and up-regulation of its down-stream molecules, Dickkopf-1 (DKK-1) and DKK-4 are implicated in the aggressive progression of colorectal adenocarcinomas (CRC). In this study, the expression of these molecules was evaluated in sporadic CRCs, and their expression levels were assessed for correlation with patient prognosis. Methods: By the qRT-PCR, 98 CRCs and matching normal tissues were analyzed for expression of VDR, DKK-1, and DKK-4 at the mRNA level. These levels were normalized to b-actin expression and calculated as ratios of copy numbers. The expression levels were assessed for correlation with clinicopathological features and for their prognostic importance. The survival probabilities were estimated by the Kaplan-Meier method. Results: VDR expression was 1.5 times lower in CRCs (53 of 98, 54%) than in their corresponding normal tissues. Expression of DKK-1 was found in 51 of 98 (52%) of the CRCs and in 29 of 98 (29%) of the normal tissues. Expression of DKK-4 was found in only 14 of 98 (14%) of the CRCs and in none of the normal tissues. VDR expression was 2.0 fold lower in tumors that exhibited metastasis, and poor differentiation and in large tumors ( > 5) cm as compared to tumors without metastasis, well or moderately differentiated tumors and tumors of small size (< 5 cm), respectively. In contrast, increased (3-fold) expression of DKK-1 and DKK-4 was observed in tumors with distant and/or nodal metastases as compared to tumors without such metastases. Expression of DKK-1 was higher in tumors with poor differentiation and in large tumors. There was an inverse relationship between VDR and DKK-4 expression. Survival analyses suggested that CRCs expressing DKK-1 (log rank, P = 0.046) and those with decreased or lack of expression of VDR (log rank, P = 0.043) were associated with poor patient survival. There was, however, no prognostic value for DKK-4 expression (log rank P=0.624). Conclusions: These findings suggest that, for CRCs, increased expression of DKK-1 and reduced or lack of expression of VDR, are associated with aggressiveness and with a poor prognosis for patients. These results provide evidence augmenting the VDR-DKK- pathway may represent a rational therapeutic strategy in colorectal carcinoma. No significant financial relationships to disclose.


2021 ◽  
Vol 12 (1) ◽  
pp. 306
Author(s):  
Justyna Durślewicz ◽  
Anna Klimaszewska-Wiśniewska ◽  
Ewa Domanowska ◽  
Natalia Skoczylas-Makowska ◽  
Paulina Antosik ◽  
...  

The present study aimed to explore the role of SATB1, SMAD3, Ezrin and β-catenin as individual and combined biomarkers for the survival prediction in pancreatic adenocarcinoma (PAC). Notably, this study distinguished for the first time a potential prognostic value of SATB1 corresponding to its subcellular localization in PAC. Immunohistochemical staining on tissue macroarrays, as well as RNA-seq data from public sources, were investigated, and the results correlated with overall survival (OS) and clinicopathological features. The connectivity between the examined factors, as well as their common signaling pathways, were demonstrated by the functional enrichment analysis. Herein, the prognostic ability of cytoplasmic SATB1 in OS analysis was even superior to nuclear SATB1. Both staining patterns tended to have opposite roles in the prognosis of PAC: SATB1c was an independent prognostic factor for poor OS, whereas SATB1n expression reached no statistical significance, but Kaplan–Meier curves separated patients with low expression and adverse prognosis from patients with high expression and favorable prognosis. High levels of SATB1 mRNA appeared as an independent prognostic indicator for better OS. Furthermore, individual expression of SMAD3 or Ezrin, as well as combined expression of SATB1/SMAD3/Ezrin/β-catenin, were associated with OS independently of conventional risk factors, both in our cohort and TCGA dataset. In our series, patients with tumors harboring combined expression of SATB1n-high/SMAD3low/Ezrinlow/β-cateninlow experienced the highest survival rates, while those with SATB1c-present/SMAD3high/Ezrinhigh/β-cateninhigh had the worst survival. In conclusion, protein and/or mRNA expression levels of SATB1, SMAD3, Ezrin and β-catenin may serve as potential prognostic biomarkers for PAC, both as single predictors and even better when combined.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chengwu Xiao ◽  
Wei Zhang ◽  
Meimian Hua ◽  
Huan Chen ◽  
Bin Yang ◽  
...  

Abstract Background The tripartite motif (TRIM) family proteins exhibit oncogenic roles in various cancers. The roles of TRIM27, a member of the TRIM super family, in renal cell carcinoma (RCC) remained unexplored. In the current study, we aimed to investigate the clinical impact and roles of TRIM27 in the development of RCC. Methods The mRNA levels of TRIM27 and Kaplan–Meier survival of RCC were analyzed from The Cancer Genome Atlas database. Real-time PCR and Western blotting were used to measure the mRNA and protein levels of TRIM27 both in vivo and in vitro. siRNA and TRIM27 were exogenously overexpressed in RCC cell lines to manipulate TRIM27 expression. Results We discovered that TRIM27 was elevated in RCC patients, and the expression of TRIM27 was closely correlated with poor prognosis. The loss of function and gain of function results illustrated that TRIM27 promotes cell proliferation and inhibits apoptosis in RCC cell lines. Furthermore, TRIM27 expression was positively associated with NF-κB expression in patients with RCC. Blocking the activity of NF-κB attenuated the TRIM27-mediated enhancement of proliferation and inhibition of apoptosis. TRIM27 directly interacted with Iκbα, an inhibitor of NF-κB, to promote its ubiquitination, and the inhibitory effects of TRIM27 on Iκbα led to NF-κB activation. Conclusions Our results suggest that TRIM27 exhibits an oncogenic role in RCC by regulating NF-κB signaling. TRIM27 serves as a specific prognostic indicator for RCC, and strategies targeting the suppression of TRIM27 function may shed light on future therapeutic approaches.


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