scholarly journals KRAS Mutation as a Potential Prognostic Biomarker of Biliary Tract Cancers

2016 ◽  
Vol 7 ◽  
pp. JCM.S40549 ◽  
Author(s):  
Masaaki Yokoyama ◽  
Hiroaki Ohnishi ◽  
Kouki Ohtsuka ◽  
Satsuki Matsushima ◽  
Yasuo Ohkura ◽  
...  

Background The aim of this study was to identify the unique molecular characteristics of biliary tract cancer (BTC) for the development of novel molecular-targeted therapies. Materials and Methods We performed mutational analysis of KRAS, BRAF, PIK3CA, and FBXW7 and immunohistochemical analysis of EGFR and TP53 in 63 Japanese patients with BTC and retrospectively evaluated the association between the molecular characteristics and clinicopathological features of BTC. Results KRAS mutations were identified in 9 (14%) of the 63 BTC patients; no mutations were detected within the analyzed regions of BRAF, PIK3CA, and FBXW7. EGFR overexpression was observed in 5 (8%) of the 63 tumors, while TP53 overexpression was observed in 48% (30/63) of the patients. Overall survival of patients with KRAS mutation was significantly shorter than that of patients with the wild-type KRAS gene ( P = 0.005). By multivariate analysis incorporating molecular and clinicopathological features, KRAS mutations and lymph node metastasis were identified to be independently associated with shorter overall survival ( KRAS, P = 0.004; lymph node metastasis, P = 0.015). Conclusions Our data suggest that KRAS mutation is a poor prognosis predictive biomarker for the survival in BTC patients.

2021 ◽  
pp. 1-15
Author(s):  
Gabriel da Silva ◽  
Leandro Luongo de Matos ◽  
Luiz Paulo Kowalski ◽  
Marco Kulcsar ◽  
Andreia Machado Leopoldino

BACKGROUND: Sphingolipids are bioactive lipids that play a role in cancer development. However, the clinical role of sphingolipid (SPL)-related genes in oral cancer (OC) remains not fully understood. OBJECTIVE: This study, aimed to examine the mRNA expression of 14 sphingolipid-related genes in oral cancer patients and their implication with clinicopathological features and prognosis. METHODS: qPCR analysis was performed in 50 OC tissues and their matched surgical margins. Next, Kaplan-Meier, Cox regression, and Receiver operating characteristics (ROC) analysis were applied to evaluate the impact of sphingolipid-related genes expression on the prognosis of OC. RESULTS: The genes SET, ACER3, SK1 and S1PR5 were predominantly up-regulated, while ABCG2, S1PR1, ABCB1 and SPNS2 were down-regulated in OC patients. Analyzing the Cancer Genome Atlas Head-Neck Squamous Cell Carcinoma (TCGA-HNSC) data, which are predominantly composed of OC samples, these genes displayed a similar profile. In OC patients, high levels of SK1 were associated with lymph node metastasis, extracapsular invasion, desmoplasia, locoregional relapse, and disease status. Low levels of SPNS2 were associated with lymph node metastasis, perineural invasion, and disease status. Furthermore, OC and HNSC patients with higher SK1 expression demonstrated shorter disease-free survival (p= 0.0037; p= 0.0087), whereas those with lower SPNS2 expression exhibited shorter overall survival (p= 0.051; p= 0.0012). High levels of ACER3 and low levels of S1PR1 were associated with shorter disease-free and overall survival in HNSC patients. CONCLUSION: Several sphingolipid-related genes are deregulated in OC at the mRNA level and are associated with clinicopathological features and presented potencial for the prediction of poor prognosis in OC patients.


2020 ◽  
Author(s):  
Yongfeng Li ◽  
Xinmiao Rui ◽  
Daobao Chen ◽  
Haojun Xuan ◽  
Hongjian Yang ◽  
...  

Abstract Background: Long noncoding RNA associated with poor prognosis of hepatocellular carcinoma (AWPPH) is a novel oncogene and dysregulated in a variety of human cancers. It has been revealed to be associated with the clinicopathological features and prognosis. However, the prognostic value of AWPPH in various cancers remains unclear. Therefore, we perform this meta-analysis to evaluate the relationship between AWPPH expression and clinical outcomes in human cancers.Methods: Comprehensive literature search was performed in PubMed, Web of Science, CNKI and Wangfang databases, and eligible studies were obtained according to the inclusion and exclusion criteria. The pooled hazard ratios (HRs) and odds ratios (ORs) were applied to assess the clinical value of AWPPH expression for overall survival (OS) and clinicopathological features.Results: A total of 19 articles including 1699 cancer patients were included in the study. The pooled results demonstrated that evaluated AWPPH expression was positively related to a poorer overall survival of patients with cancers (HR=1.79, 95%CI: 1.44-2.14, P<0.001). Subgroup analysis revealed that tumor type and sample size affect the predictive value of AWPPH on OS, whereas cut-off value and HR estimation method have no impact on it. In addition, the pooled data also showed that AWPPH was positively linked to advanced TNM stage (OR=2.67, 95%CI: 1.86-3.83, P<0.001) , bigger tumor size (OR=2.64, 95%CI:1.47-4.73, P=0.001), macro-vascular invasion (OR=2.08, 95%CI: 1.04-4.16, P=0.04) and lymph node metastasis (OR=2.68, 95%CI: 1.82-3.96, P<0.001). Moreover, the results of the trim and fill analysis confirmed the reliability of our finding. Conclusions: Upregulation of AWPPH was associated with advanced TNM stage, bigger tumor size, worse lymph node metastasis, macro-vascular invasion, and shorter overall survival, suggesting that AWPPH may serve as a biomarker for prognosis and clinicopathological characteristics in human cancers.


1994 ◽  
Vol 31 (1) ◽  
pp. 119
Author(s):  
Young Soo Do ◽  
Byung Hee Lee ◽  
Kie Hwan Kim ◽  
Soo Yil Chin ◽  
Ah Ra Lee

2010 ◽  
Vol 20 (6) ◽  
pp. 1000-1005 ◽  
Author(s):  
Masamichi Hiura ◽  
Takayoshi Nogawa ◽  
Takashi Matsumoto ◽  
Takashi Yokoyama ◽  
Yuko Shiroyama ◽  
...  

Objective:The purposes of this study were to assess modified radical hysterectomy including systematic pelvic and para-aortic lymphadenectomy followed by adjuvant chemotherapy in patients with para-aortic lymph node (PAN) metastasis in endometrial carcinoma and to identify the multivariate independent prognostic factors for long-term survival during the past 10 years.Methods:Between December 1987 and December 2002, we performed modified radical hysterectomy with bilateral salpingo-oophorectomy including systematic pelvic and para-aortic lymphadenectomy and peritoneal cytology in 284 endometrial carcinoma patients according to the classification of the International Federation of Gynecology and Obstetrics (stage IA, n = 66; stage IB, n = 96; stage IC, n = 33; stage IIA, n = 5; stage IIB, n = 20; stage IIIA, n = 28; stage IIIC, n = 28; and stage IV, n = 8) who gave informed consents at our institute. Patients with tumor confined to the uterus (stages IC and II) were treated by 3 courses of cyclophosphamide 750 mg/m2, epirubicin 50 mg/m2, and cisplatin 75 mg/m2 regimen 3 to 4 weeks apart, and patients with extrauterine lesions involving adnexa and/or pelvic lymph node (PLN) were treated by 5 courses. In addition, 10 courses were given to patients with PAN metastasis. Patients with PLN metastasis received adjuvant chemotherapy, and adjuvant radiation was not part of our institutional protocol. For multivariate regression modeling with proportional hazards, the regression model of Cox was used. Survival curves were analyzed by the Kaplan-Meier method, and analysis of the differences was performed by the log-rank test.Results:The overall incidence of retroperitoneal lymph node metastasis assessed by systematic pelvic and para-aortic lymphadenectomy was 12.0% (34/284) in stages I to IV endometrial carcinoma, and incidences of PLN and PAN metastases were 9.2% (26/284) and 7.4% (21/284), respectively. However, PAN metastasis rate is 50% (13/26) in patients with PLN metastasis. Univariate analysis of prognostic factors revealed that International Federation of Gynecology and Obstetrics clinical stage (P < 0.0001), histological finding (P = 0.0292), myometrial invasion (P < 0.0001), adnexal metastasis (P < 0.0001), lymphovascular space invasion (P < 0.0001), tumor diameter (P = 0.0108), peritoneal cytology (P = 0.0001), and retroperitoneal lymph node metastasis (P < 0.0001) were significantly associated with 10-year overall survival. Survival was not associated with age (P = 0.1558) or cervical involvement (P = 0.1828). A multivariate analysis showed that adnexal metastasis (P = 0.0418) and lymphovascular space invasion (P = 0.0214) were significantly associated with 10-year overall survival. The 5- and 10-year overall survival rates in patients with negative PAN were 96% and 93% versus 72% and 62% in patients with positive PAN (P = 0.006).Conclusions:It is suggested that surgery with systematic pelvic and para-aortic lymphadenectomy followed by adjuvant chemotherapy could improve long-term survival in patients with PAN metastasis, although there are only 21 patients with PAN metastasis.


2019 ◽  
Vol 18 ◽  
pp. 153303381989680
Author(s):  
Hongxiao Chen ◽  
Xiufang Tian ◽  
Yajing Luan ◽  
Hui Lu

Emerging evidence have indicated that dysregulated long noncoding ribonucleic acids act as a novel diagnostic and therapeutic target in the progression of ovarian cancer. Long noncoding RNA DiGeorge syndrome critical region gene 5 has been reported to participate in some types of human cancer progresses, but its clinical roles in ovarian cancer had been rarely reported. This study aimed to explore the expression, clinicopathological features, diagnostic, and prognostic values of DiGeorge syndrome critical region gene 5 in ovarian cancer. The total levels of DiGeorge syndrome critical region gene 5 transcript variant 1 (NR_002733.2) and 2 (NR_045121.1) in patients with ovarian cancer were determined by quantitative reverse transcription polymerase chain reaction. The correlation of DiGeorge syndrome critical region gene 5 expression with clinicopathological factors was statistically analyzed by χ2 test. Overall survival analysis was carried out with the Kaplan–Meier curves with the log-rank test. Univariate and multivariate Cox regression analyses were performed to identify the prognostic significance of DiGeorge syndrome critical region gene 5 expression. Receiver operating characteristic curves were constructed to estimate the diagnostic and prognostic usefulness of DiGeorge syndrome critical region gene 5 in ovarian cancer. Results showed that relative DiGeorge syndrome critical region gene 5 expression was reduced by 36.81% and 65.79% in ovarian cancer tissues of patients and Gene Expression Omnibus DataSets (GSE119056) in contrast to normal tissues, respectively. Patients with lymph node metastasis and distant metastasis exhibited lower levels of DiGeorge syndrome critical region gene 5 in contrast to those patients with non-lymph node metastasis and non-distant metastasis, respectively. Low expression of DiGeorge syndrome critical region gene 5 was significantly associated with large tumor size, more lymph node metastasis, present distant metastasis, advanced clinical stage, and short overall survival in patients with ovarian cancer. Low expression of DiGeorge syndrome critical region gene 5 was an independent unfavorable prognostic factor for overall survival in patients with ovarian cancer. Receiver operating characteristics curves for prognosis yielded significant area under curves for lymph node metastasis, clinical stage, and overall survival. In conclusion, our study demonstrated that downregulated DiGeorge syndrome critical region gene 5 may be a new promising biomarker for predicting clinical progression and prognosis in patients with ovarian cancer.


2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Ahmad Aizat Abdul Aziz ◽  
Md Salzihan Md Salleh ◽  
Ravindran Ankathil

Triple negative breast cancer (TNBC) is associated with aggressive tumour phenotype and early tumour relapse following diagnosis. Generally, clinicopathological features such as tumour size, patient’s age at diagnosis, tumour histology subtypes, grade and stage, involvement of lymph nodes, and menopausal status are commonly used for predicting disease progression, prospects of recurrence, and treatment response. Prognostic value of clinicopathological features on Malaysian TNBC patients is limited. Thus, this study is aimed at investigating the association of clinicopathological features on disease-free survival (DFS) and overall survival (OS) of Malaysian TNBC patients undergoing TAC chemotherapy. Seventy-six (76) immunohistochemistry-confirmed TNBC patients were recruited. The clinicopathological features of TNBC patients were collected and recorded. Kaplan-Meier and log-rank followed by a Cox proportional hazard regression model were performed to evaluate the TNBC patients’ survival. Out of 76 TNBC patients, 25 were chemoresistant and 51 were chemoresponders to the TAC chemotherapy regimen. The overall 5-year cumulative DFS and OS of TNBC patients were 63.5% and 76.3%, respectively. Multivariate Cox analysis demonstrated that medullary and metaplastic histology subtypes and positive axillary lymph node metastasis were significant prognostic factors associated with relapse with adjusted HR: 5.76, 95% CI: 2.35, 14.08 and adjusted HR: 3.55, 95% CI: 1.44, 8.74, respectively. Moreover, TNBC patients with medullary and metaplastic histology subtypes and positive axillary lymph node metastases had a higher risk to death than patients who had infiltrating ductal carcinoma and negative axillary lymph node metastasis (adjusted HR: 8.30, 95% CI: 2.38, 28.96 and adjusted HR: 6.12, 95% CI: 1.32, 28.42, respectively). Our results demonstrate the potential use of medullary and metaplastic histology subtype and positive axillary lymph node metastasis as a potential biomarker in predicting relapse and survival of the TNBC patients. This warrants further studies on intensification of chemotherapy and also identification and development of targeted therapy to reduce relapses and improve survival of TNBC patients.


2008 ◽  
Vol 97 (5) ◽  
pp. 423-427 ◽  
Author(s):  
Haruki Morimoto ◽  
Tetsuo Ajiki ◽  
Takashi Ueda ◽  
Hidehiro Sawa ◽  
Tsunenori Fujita ◽  
...  

2020 ◽  
Vol 86 (2) ◽  
pp. 164-170
Author(s):  
Peilin Zheng ◽  
Chen Lai ◽  
Weimin Yang ◽  
Zhikang Chen

Tumor deposits in colon cancer are related to poor prognosis, whereas the prognostic power of tumor deposits in combination with lymph node metastasis (LNM) is controversial. This study aimed to compare the overall survival between LNM alone and LNM in combination with tumor deposits, and to verify whether the number of tumor deposits can be considered LNM in patients with both LNM and tumor deposits in stage III colon cancer by propensity score matching (PSM). Patients carrying resected stage III adenocarcinoma of colon cancer were identified from the Surveillance, Epidemiology, and End Results database (2010–2015). The Kaplan-Meier method, Cox proportional hazard models and PSM were used. On the whole, 23,168 patients (20,451 (88.3%) with only LNM and 2,717 (11.7%) with both LNM and tumor deposits) were selected. After undergoing PSM, patients with both LNM and tumor deposits showed worse overall survival (hazard ratio = 1.33, 95% confidence interval: 1.20–1.47, P < 0.001). After the number of tumor deposits was added with that of positive regional lymph nodes, patients with both LNM and tumor deposits seemed to have prognostic implications similar to those with LNM alone (hazard ratio = 1.02, 95% confidence interval: 0.93–1.12, P = 0.66). The simultaneous presence of LNM and tumor deposits, as compared with the presence of only LNM, had an association with a worse outcome. Tumor deposits should be considered as LNM in patients with both tumor deposits and LNM in stage III colon cancer.


2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Min Li ◽  
Shuwei Wu ◽  
Yangqin Xie ◽  
Xiaohui Zhang ◽  
Zhanyu Wang ◽  
...  

Abstract Background The aim of this study is to determine pathological factors that increase the risk of LNM and indicate poor survival of patients diagnosed with endometrial cancer and treated with surgical staging. Method Between January 2010 and November 2018, we enrolled 874 eligible patients who received staging surgery in the First Affiliated Hospital of Anhui Medical University. The roles of prognostic risk factors, such as age, histological subtype, tumor grade, myometrial infiltration, tumor diameter, cervical infiltration, lymphopoiesis space invasion (LVSI), CA125, and ascites, were evaluated. Multivariable logistic regression models were used to identify the predictors of LNM. Kaplan–Meier and COX regression models were utilized to study the overall survival. Results Multivariable regression analysis confirmed cervical stromal invasion (OR 3.412, 95% CI 1.631–7.141; P < 0.01), LVSI (OR 2.542, 95% CI 1.061–6.004; P = 0.04) and ovarian metastasis (OR 6.236, 95% CI 1.561–24.904; P = 0.01) as significant predictors of nodal dissemination. Furthermore, pathological pattern (P = 0.03), myometrial invasion (OR 2.70, 95% CI 1.139–6.40; P = 0.01), and lymph node metastasis (OR 9.675, 95% CI 3.708–25.245; P < 0.01) were independent predictors of decreased overall survival. Conclusions Cervical invasion, lymphopoiesis space invasion, and ovarian metastasis significantly convey the risk of LNM. Pathological type, myometrial invasion, and lymph node metastasis are all important predictors of survival and should be scheduled for completion when possible in the surgical staging procedure.


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