Somatic genetic aberrations in gallbladder cancer: comparison between Chinese and US patients

Yang, Po; Javle, Milind; Pang, Fei; Zhao, Wei; Abdel-Wahab, Reham; Chen, Xiaofeng; Meric‐Bernstam, Funda; Chen, Huanwei; Borad, Mitesh J.; Liu, Yu; Zou, Chuntao; Mu, Shuo; Xing, Yanfeng; Wang, Kai; Peng, Chuang; Che, Xu

doi:10.21037/hbsn.2019.04.11

Cited by 35 publications

(25 citation statements)

References 32 publications

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“…However, these models were based on analyses of the SEER database, and patients’ characteristics may differ from patients in other areas. More studies have been proposed regarding patients’ gene expression levels, but these methods are not convenient to use clinically[ 31 - 33 ]; thus, an appropriate model to evaluate the prognosis of GBC patients in China is still an urgent need.…”

Section: Discussionmentioning

confidence: 99%

γ-glutamyl transferase-to-platelet ratio based nomogram predicting overall survival of gallbladder carcinoma

Sun¹,

Guan²,

Xu³

et al. 2020

WJGO

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BACKGROUND Gallbladder carcinoma (GBC) carries a poor prognosis and requires a prediction method. Gamma-glutamyl transferase–to–platelet ratio (GPR) is a recently reported cancer prognostic factor. Although the mechanism for the relationship between GPR and poor cancer prognosis remains unclear, studies have demonstrated the clinical effect of both gamma-glutamyl transferase and platelet count on GBC and related gallbladder diseases. AIM To assess the prognostic value of GPR and to design a prognostic nomogram for GBC. METHODS The analysis involved 130 GBC patients who underwent surgery at Peking Union Medical College Hospital from December 2003 to April 2017. The patients were stratified into a high- or low-GPR group. The predictive ability of GPR was evaluated by Kaplan–Meier analysis and a Cox regression model. We developed a nomogram based on GPR, which we verified using calibration curves. The nomogram and other prognosis prediction models were compared using time-dependent receiver operating characteristic curves and the concordance index. RESULTS Patients in the high-GPR group had a higher risk of jaundice, were older, and had higher carbohydrate antigen 19-9 levels and worse postoperative outcomes. Univariate analysis revealed that GPR, age, body mass index, tumor–node–metastasis (TNM) stage, jaundice, cancer cell differentiation degree, and carcinoembryonic antigen and carbohydrate antigen 19-9 levels were related to overall survival (OS). Multivariate analysis confirmed that GPR, body mass index, age, and TNM stage were independent predictors of poor OS. Calibration curves were highly consistent with actual observations. Comparisons of time-dependent receiver operating characteristic curves and the concordance index showed advantages for the nomogram over TNM staging. CONCLUSION GPR is an independent predictor of GBC prognosis, and nomogram-integrated GPR is a promising predictive model for OS in GBC.

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Section: Discussionmentioning

confidence: 99%

γ-glutamyl transferase-to-platelet ratio based nomogram predicting overall survival of gallbladder carcinoma

Sun¹,

Guan²,

Xu³

et al. 2020

WJGO

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“…is significantly higher (8.3% vs. 1.9%, p = .03%) [17]. Therefore, the evidence of efficacy of olaparib for treating individuals with ATM-inactivation is more adequate.…”

Section: Genotyping Results and Interpretation Of The Molecular Resultsmentioning

confidence: 94%

Effectiveness of Olaparib Treatment in a Patient with Gallbladder Cancer with an ATM-Inactivating Mutation

Zhang

Shi

et al. 2020

The Oncologist

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Here, we report a case of postoperative recurrence of gallbladder carcinoma (GBC) in a patient who declined systemic chemotherapy. ATM S1905Ifs*25 and STK11 K262Sfs*25 mutations were detected by next-generation sequencing. Oral administration of olaparib was initiated. One month later, the patient experienced relief of clinical symptoms, a decrease in CA19-9 level, and a reduction in abnormal signal in the subcapsular region. The tumor response remained stable for approximately 13 months. This is the first case to demonstrate the clinical benefits of olaparib treatment in a patient with GBC harboring an ATM-inactivating mutation. This observation helps to better inform treatment options to enhance the care of patients with advanced GBC. The Oncologist 2020;25:375-379 KEY POINTS • A patient with gallbladder carcinoma harboring an ATM-inactivating mutation responded to olaparib with a progression-free survival of 13 months. • This is the first report that demonstrates the clinical benefits of olaparib treatment in a patient with gallbladder carcinoma with an ATM-inactivating mutation. • It also highlights the importance of next-generation sequencing, which can provide valuable information for planning effective targeted therapies for gallbladder carcinoma. • Evidence-based decisions help determine the best choice of treatment for individualized patient care.

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“…320 More interestingly, the coincidence of ERBB2 genetic mutations with CDKN2A/B variations in US patients was stronger (odds ratio 10.8, P = 0.0001) than those in Chinese cohort (odds ratio 5.4, P = 0.0014), which suggests that CDKN2A/B alterations were significantly associated with distant metastases. 321 Our previous study showed that CDKN2A/B mutation rate was~5.9% in GBC. 58,228 There were other reports supporting the notion that CDKN2A/B mutations mediate the pathogenesis of GBC.…”

Section: Tp53mentioning

confidence: 95%

Overview of current targeted therapy in gallbladder cancer

Song

et al. 2020

Sig Transduct Target Ther

106

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Gallbladder cancer (GBC) is rare, but is the most malignant type of biliary tract tumor. Unfortunately, only a small population of cancer patients is acceptable for the surgical resection, the current effective regimen; thus, the high mortality rate has been static for decades. To substantially circumvent the stagnant scenario, a number of therapeutic approaches owing to the creation of advanced technologic measures (e.g., next-generation sequencing, transcriptomics, proteomics) have been intensively innovated, which include targeted therapy, immunotherapy, and nanoparticle-based delivery systems. In the current review, we primarily focus on the targeted therapy capable of specifically inhibiting individual key molecules that govern aberrant signaling cascades in GBC. Global clinical trials of targeted therapy in GBC are updated and may offer great value for novel pathologic and therapeutic insights of this deadly disease, ultimately improving the efficacy of treatment.

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Somatic genetic aberrations in gallbladder cancer: comparison between Chinese and US patients

Cited by 35 publications

References 32 publications

γ-glutamyl transferase-to-platelet ratio based nomogram predicting overall survival of gallbladder carcinoma

γ-glutamyl transferase-to-platelet ratio based nomogram predicting overall survival of gallbladder carcinoma

Effectiveness of Olaparib Treatment in a Patient with Gallbladder Cancer with an ATM-Inactivating Mutation

Overview of current targeted therapy in gallbladder cancer

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