scholarly journals Bioinformatic Identification of Potential Hub Genes in Muscle-Invasive Bladder Urothelial Carcinoma

2020 ◽  
Vol 29 ◽  
pp. 096368972096517
Author(s):  
Changgang Guo ◽  
Ting Shao ◽  
Dadong Wei ◽  
Chunsheng Li ◽  
Fengjun Liu ◽  
...  

Despite aggressive treatment approaches, muscle-invasive bladder urothelial carcinoma (MIBC) patients still have a 50% chance of developing general incurable metastases. Therefore, there is an urgent need for candidate markers to enhance diagnosis and generate effective treatments for this disease. We evaluated four mRNA microarray datasets to find differences between non-MIBC (NMIBC) and MIBC tissues. Through a gene expression profile analysis via the Gene Expression Omnibus database, we identified 56 differentially expressed genes (DEGs). Enrichment analysis of gene ontology, Kyoto Encyclopedia of Genes and Genomes, and Reactome pathways revealed the interactions between these DEGs. Next, we established a protein-protein interaction network to determine the interrelationship between the DEGs and selected 10 hub genes accordingly. Bladder urothelial carcinoma (BLCA) patients with COL1A2, COL5A1, and COL5A2 alterations showed poor disease-free survival rates, while BLCA patients with COL1A1 and LUM alterations showed poor overall survival rates. Oncomine analysis of MIBC versus NMIBC tissues showed that COL1A1, COL5A2, COL1A2, and COL3A1 were consistently among the top 20 overexpressed genes in different studies. Using the TCGAportal, we noted that the high expression of each of the four genes led to shorter BLCA patient overall survival. It was evident that BLCA patients with an elevated high combined gene expression had significantly shorter overall survival and relapse-free survival than those with low combined gene expression using PROGgeneV2. Using Gene Expression Profiling Interactive Analysis, we noted that COL1A1, COL1A2, COL3A1, and COL5A2 were positively correlated with each other in BLCA. These genes are considered as clinically relevant genes, suggesting that they may play an important role in the carcinogenesis, development, invasion, and metastasis of MIBC. However, considering we adopted a bioinformatic approach, more research is crucial to confirm our results. Nonetheless, our findings may have important prospective clinical implementations.

Oncotarget ◽  
2018 ◽  
Vol 9 (51) ◽  
pp. 29743-29752 ◽  
Author(s):  
Kevin B. Givechian ◽  
Chad Garner ◽  
Hermes Garban ◽  
Shahrooz Rabizadeh ◽  
Patrick Soon-Shiong

2019 ◽  
Vol 18 ◽  
pp. 153303381987660 ◽  
Author(s):  
Yu Ding ◽  
Qifeng Cao ◽  
Chen Wang ◽  
Huangqi Duan ◽  
Haibo Shen

Background: To identify the hub genes related to urothelial carcinoma of the bladder prognosis and to understand their underlying mechanism. Methods: The expression profiles of 18 pairs of urothelial carcinoma of the bladder patient tissue and paired adjacent tissue obtained from the Cancer Genome Atlas were performed. Weighted gene coexpression network analysis was employed to screen gene modules and hub genes with significant differential expressions in urothelial carcinoma of the bladder. The hub genes expression in urothelial carcinoma of the bladder tissues was validated by reverse transcription-quantitative polymerase chain reaction. The overall survival curve and disease-free survival curve of prognostic factor ( LGALS4) were plotted using the Kaplan-Meier method. Furthermore, LGALS4 messenger RNA and protein expression were also assessed in 2 urothelial carcinoma of the bladder cell lines (T24 and 5637) by quantitative reverse transcription–polymerase chain reaction and Western blot. The functions of urothelial carcinoma of the bladder cells with transfected pcDNA3.1- LGALS4 were identified through MTT assay, plate clone formation assay, flow cytometry, and cell migration experiments. Results: LGALS4 was the hub gene of pink module and it was related to prognosis. Higher LGALS4 expression predicted higher probabilities of overall survival and disease-free survival. Overexpression of LGALS4 in urothelial carcinoma of the bladder cells suppressed cell viability and migration but induced apoptosis. Conclusion: LGALS4 played a critical role in the progression of urothelial carcinoma of the bladder and held a promise to be the biomarker for diagnosis and treatment of urothelial carcinoma of the bladder. It predicted good prognosis of urothelial carcinoma of the bladder and restrained the growth and migration of urothelial carcinoma of the bladder cells.


2012 ◽  
Vol 31 (1) ◽  
pp. 5-11 ◽  
Author(s):  
Harun Fajkovic ◽  
Eugene K. Cha ◽  
Evanguelos Xylinas ◽  
Michael Rink ◽  
Armin Pycha ◽  
...  

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5517-5517 ◽  
Author(s):  
A. A. Forastiere ◽  
M. Maor ◽  
R. S. Weber ◽  
T. Pajak ◽  
B. Glisson ◽  
...  

5517 Background: The 2-year results of Intergroup RTOG 91–11 were published in 2003 (NEJM 349:2091–8,2003). We now present the 5-year results (after median follow-up for surviving patients of 6.9 years) of 515 eligible pts with resectable stage III or IV (excluding T1 and high volume T4), cancer of the glottic or supraglottic larynx. Methods: Patients were randomized to induction cisplatin/5-FU (CF) with responders then receiving RT (I+RT) (n = 173); or concurrent cisplatin (100 mg/m2 q 21 days × 3) and RT (CRT) (n = 171); or RT alone (R) (n = 171). Laryngectomy was performed for < partial response to induction CF, for persistent/recurrent disease or for laryngeal dysfunction. Results: At 5 years, laryngectomy-free survival (LFS) was significantly better with either I+RT (44.6%, p = 0.011) or CRT (46.6%, p = 0.011) compared to R (33.9%). There was no difference in LFS between I+RT and CRT (p = 0.98). Laryngeal preservation (LP) was significantly better with CRT (83.6%) compared to I+RT (70.5%, p = 0.0029) or R (65.7%, p = 0.00017). Local-regional control (LRC) was significantly better with CRT (68.8%) compared to I+RT (54.9%, p = 0.0018) or R (51%, p = 0.0005). I+RT compared to R for LP and LRC showed no significant difference (p = 0.37 and 0.62, respectively). The distant metastatic rate was low (I+RT 14.3%, CRT 13.2%, R 22.3%) with a trend (p ∼0.06) for benefit from chemotherapy. Disease-free survival (DFS) was significantly better with either I+RT (38.6%, p = 0.016) or CRT (39%, p = 0.0058) compared to R (27.3%). Overall survival rates were similar for the first 5 years (I+RT 59.2%, CRT 54.6%, R 53.5%); thereafter I+RT had a non-significant lower death rate. Compared to CRT, significantly more pts in the R group died of their cancer (34% vs 58.3%, p = 0.0007); the rate for I+RT was 43.8%. Conclusion: These 5-year results differ from the 2-year analysis by a significant improvement in LFS now seen for both I+RT and CRT treatments compared to R. For the endpoints of LP and LRC, CRT is still the superior treatment with no advantage seen to the addition of induction CF to R. There is no significant difference in overall survival. [Table: see text]


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Chun-Kai Liao ◽  
Yen-Lin Yu ◽  
Yueh-Chen Lin ◽  
Yu-Jen Hsu ◽  
Yih-Jong Chern ◽  
...  

Abstract Backgrounds The inflammatory biomarker “C-reactive protein to albumin ratio (CAR)” has been reported to significantly correlate to a variety of human cancers. However, there are conflicting results regarding the prognostic value of CAR in colorectal cancer. Previous studies mainly assessed patients in Eastern countries, so their findings may not be applicable to the Western population. Therefore, this updated meta-analysis aimed to investigate the prognostic value of pre-treatment CAR and outcomes of patients with colorectal cancer. Methods We conducted a systematic search for eligible literature until October 31, 2020, using PubMed and Embase databases. Studies assessing pre-treatment CAR and outcomes of colorectal cancer were included. Outcome measures included overall survival, disease-free survival, progression-free survival, and clinicopathological features. The pooled hazard ratios (HR) with 95% confidence intervals (CI) were used as effective values. Results A total of 15 studies involving 6329 patients were included in this study. The pooled results indicated that a high pre-treatment CAR was associated with poor overall survival (HR 2.028, 95% CI 1.808−2.275, p < 0.001) and poor disease-free survival/progression-free survival (HR 1.768, 95% CI 1.321–2.365, p < 0.001). Subgroup analysis revealed a constant prognostic value of the pre-treatment CAR despite different study regions, sample size, cancer stage, treatment methods, or the cut-off value used. We also noted a correlation between high pre-treatment CAR and old age, male sex, colon cancer, advanced stage (III/IV), large tumor size, poor differentiation, elevated carcinoembryonic antigen levels, neutrophil-to-lymphocyte ratio, and the modified Glasgow prognostic score. Conclusions High pre-treatment CAR was associated with poor overall survival, disease-free survival, and progression-free survival in colorectal cancer. It can serve as a prognostic marker for colorectal cancer in clinical practice.


2020 ◽  
Author(s):  
Chengyu Luo ◽  
Guang Cao ◽  
wenbin Guo ◽  
Jie Yang ◽  
Qiuru Sun ◽  
...  

Abstract Backgroud: Longer follow-up was necessary to testify the exact value of mastoscopic axillary lymph node dissection (MALND).Methods:From January 1, 2003 to December 31, 2005,1027 patients with operable breast cancer were randomly assigned to two groups: MALND and CALND. 996 eligible patients were enrolled. The end points are disease free survival and overall survival.Results:The final cohort of 996 patients was followed for an average of 184 months. The distribution of all events was fairly similar between two groups of patients. The incidence of local in-breast events did not differ in a significant manner between two cohorts. Similarly, the rate of distant metastases was not significantly different with 30.0% in MLND and 32.6% in CALND. And no significant difference was observed in other primary tumor between two groups (p=0.46). Patients who remain alive with no event comprise a total of 37.2% in MALND and 35.4% in CALND. Other primary cancers and deaths from other causes were distributed equally between two groups. The 15-year disease-free survival rates were41.1 percent for the MALND group and 39.6 percent for the CALND group (p=0.79). MALND was found to be not inferior for overall survival (P =0.54). The 15-year overall survival rates were 49.5 percentafter MALND and 51.2 percentafter CALND (p=0.86). Probability of overall survival was not significantly different between two groups.Conclusions:MALND does not increase unfavorable events, and also does not affect the long-term survival of patients. Therefore, MALND should be one of the preferred approaches for breast cancer surgery.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16100-e16100
Author(s):  
T. Koie ◽  
H. Yamamoto ◽  
A. Okamoto ◽  
S. Hatakeyama ◽  
A. Momose ◽  
...  

e16100 Background: The neoadjuvant M-VAC followed by radical cystectomy for muscle-invasive bladder cancer has improved survival compared to radical cystectomy alone. Nevertheless, M-VAC has been associated with severe toxicity. The objective of this retrospective study was to evaluate the objective response rate, the impact on overall survival, disease-free survival, disease-free survival and toxicity adverse events of gemcitabine and carboplatin (GC) neoadjuvant chemotherapy in patients with locally advanced bladder cancer. Methods: We reviewed the clinical and pathological data of 140 patients who underwent radical cystectomy and bilateral pelvic lymphadenectomy for T2N0M0 to T4aN0M0 bladder cancer at our institution between January 2001 and August 2008. Seventy patients were treated with neoadjuvant GC followed by cystectomy between March 2005 and August 2008 (GC group), and 70 patients were treated with cystectomy alone between January 2001 and May 2007 (cystectomy alone group). In the GC group, the patients received 2 courses of GC therapy consisted of 800mg/m2 gemcitabine on days 1, 8, and 15 and carboplatin (AUC 4) on day 2. The primary endpoint was the objective response rate, and the secondary endpoints were overall survival, cancer-specific survival, disease free survival, and toxicity. Results: Fifteen patients (23.8%) had a complete response and 26 patients (41.3%) had a partial response in the GC group. At a mean follow-up period of 26.7 months, the overall survival was 85.0% in the GC group and 47.8% in the cystectomy alone group (p = 0.003). The cancer-specific survival was 78.4% in the GC group and 44.6% in the cystectomy alone group (p = 0.0018). The disease-free survival was 82.9% in the GC group and 35.7% in the cystectomy alone group (p = 0.0001). Hematologic toxicities were the main adverse events. Grade 3/4 neutropenia occurred in 26 patients (37.1%) and thrombocytopenia in 15 (21.4%). There was no grade 3/4 gastrointestinal toxicity and no renal function abnormalities. Conclusions: Although this is not a randomized study, the GC neoadjuvant therapy followed by radical cystectomy is feasible and may be associated with improved survival among patients with muscle-invasive bladder cancer. A randomized trial is warranted. No significant financial relationships to disclose.


2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 376-376
Author(s):  
Yongjune Lee ◽  
Young Seok Kim ◽  
Bumsik Hong ◽  
Yong Mee Cho ◽  
Jae-Lyun Lee

376 Background: Prospective randomized trials demonstrated efficacy of MVAC (Methotrexate, Vinblastine, Doxorubicin, Cisplatin) neoadjuvant chemotherapy (NAC) in muscle invasive bladder cancer (MIBC). In metastatic setting urothelial cell carcinoma (UCC), clinical trials showed no difference in oncologic outcomes between Gemcitabine-Cisplatin (GC) and MVAC, and another prospective trial proved dose-dense (dd) MVAC had significantly better overall survival (OS) and response rate then MVAC. Comparative data between GC and ddMVAC are limited in neoadjuvant setting. Methods: A retrospective analysis of patients with urothelial carcinoma (cT2-4aN0-1M0) who received NAC from January 2011 and December 2017 in Asan Medical Center was conducted. Patients who received GC were compared to patients received ddMVAC in terms of outcomes including downstaging ( < ypT2 and no N upstaging), pathologic complete response (pCR, ypT0N0), disease-free survival (DFS), and overall survival (OS) and tolerability. Results: In a total of 277 patients, 176 patients received NAC with GC and 41 patients with dose-dense MVAC. The median chemotherapy cycle is 4 (IQR 3-4) cycles for GC group, 4 (IQR 3-5.5) cycles for dose-dense MVAC group. With an exception of age; GC group is associated with younger age (p = 0.002), other baseline characteristics are well balanced between groups. Downstaging rate are 50.8% in GC group, 58.1% in dose-dense MVAC group (p = 0.47). The rates of achieving ypT0 (28.7% vs 22.6%, p = 0.68), ypN0 (78.3% vs 81.5%, p = 0.39). There were no differences in overall survival (OS) at 3 year (72.2% vs 73.2%, p = 0.58), disease-free survival (DFS) at 3 years (54.9% vs 63.3%, p = 0.21) according to chemotherapy regimens. ddMVAC with prophylactic G-CSF are associated with higher incidence of febrile neutropenia (p = 0.004) than GC. NAC regimen is not independent prognostic factor for OS on multivariable analysis. Conclusions: GC regimen had no significant difference in oncologic outcomes compare to ddMVAC as NAC in UCC.


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