Correlation between BRCA1 and TopBP1 protein expression and clinical outcome of non-small cell lung cancer treated with platinum-based chemotherapy

Wang, Linrun; He, Linjuan; Wang, Yan; Li, Yinyan; Lou, Yan; Zhang, Guobing; Li, Ying; Chen, Jian

doi:10.1007/s00280-015-2773-0

Cited by 10 publications

(6 citation statements)

References 19 publications

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“…The status of KRAS mutation has also been suggested as a prognostic biomarker for advanced NSCLC patients undergoing ICIs [33]. Some molecular predictive markers have been applied for NSCLC patients with platinum-based chemotherapy, such as excision repair cross-complementing 1 (ERCC1) [34], ribonucleotide reductase subunit M1 (RRM1) [35], class III β-tubulin (TUBB3) [36] and breast cancer 1 (BRCA1) expression [37]. Another circulating biomarker, the neutrophil-to-lymphocyte ratio (NLR) has been recommended as a potential predictor for outcomes in NSCLC patients treated with nivolumab [38].…”

Section: Discussionmentioning

confidence: 99%

Pretreatment albumin/fibrinogen ratio as a promising predictor for the survival of advanced non small-cell lung cancer patients undergoing first-line platinum-based chemotherapy

Ying

Zhou

et al. 2019

BMC Cancer

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Background This study aimed to identify potential predictive factors for the survival of advanced non small-cell lung cancer (NSCLC) patients undergoing first-line platinum-based chemotherapy. Methods A total of 270 advanced NSCLC patients who underwent first-line platinum-based chemotherapy from June, 2011 to June, 2015 were enrolled. A receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive value of the albumin-to-fibrinogen ratio (AFR) for overall survival (OS). The predictive factors for survival were evaluated by univariate and multivariate analyses via the Cox proportional hazards regression model. The OS and progression free survival (PFS) results were determined via the Kaplan–Meier method using the log-rank analysis. Results Based on the results of the ROC curve analysis, 8.02 was accepted as the cut-off AFR value for OS. The metastasis stage (M0 vs M1a/b, HR: 1.73, 95% CI: 1.15–2.59, P = 0.020) and AFR (≤8.02 vs > 8.02, HR: 1.80, 95% CI: 1.09–2.78, P = 0.025) were two independent risk factors for PFS by multivariate Cox regression analysis. The AFR (≤8.02 vs > 8.02, HR: 1.79, 95% CI: 1.11–2.59, P = 0.029) was a significant predictive factor for OS in advanced NSCLC patients. The PFS ( P = 0.008) and OS ( P = 0.003) in the high AFR group were significantly improved compared with those in the low AFR group via the Kaplan–Meier method using the log-rank analysis. Conclusions The AFR could be a potential effective predictive factor for the survival in advanced NSCLC patients undergoing first-line platinum-based chemotherapy.

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Section: Discussionmentioning

confidence: 99%

Pretreatment albumin/fibrinogen ratio as a promising predictor for the survival of advanced non small-cell lung cancer patients undergoing first-line platinum-based chemotherapy

Ying

Zhou

et al. 2019

BMC Cancer

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“…PTPRJ is expressed in CRC cells, and it is reported that the sustained inhibition of PTPRJ increased cell resistance to 5-fluorouracil (5-FU)-induced apoptosis [ 43 ]. Wang et al indicated that the TopBP1 expression level was related to the prognosis of non-small cell lung cancer patients treated with platinum-based chemotherapy [ 44 ]. The CIAPIN1 R132W and PTPRJ L738 V mutations were identified among the post-FOLFOX unique mutations in case 2.…”

Section: Discussionmentioning

confidence: 99%

Comparative sequence analysis of patient-matched primary colorectal cancer, metastatic, and recurrent metastatic tumors after adjuvant FOLFOX chemotherapy

et al. 2019

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BackgroundIn the era of genome-guided personalized cancer treatment, we must understand chemotherapy-induced genomic changes in tumors. This study evaluated whether adjuvant FOLFOX chemotherapy modifies the mutational profile of recurrent colorectal cancer (CRC).MethodsWhole exome sequencing was performed on samples from primary CRC tumors, untreated metastatic tumors, and recurrent tumors following adjuvant FOLFOX chemotherapy. The samples were resected from four patients.ResultsThe number of mutations or the mutation spectrum in individual patients was nearly identical. Copy number variants persisted regardless of FOLFOX therapy administration. The genomic signature of oxaliplatin exposure (G > T/C > A, T > A/A > T) was not enriched after FOLFOX chemotherapy. Overlapping single nucleotide variants (SNVs) and indels remained in 26–65% of the patient-matched tumor samples. One patient harbored an AKT1 E17K mutation in the recurrent tumor, whereas PIK3CA E542K and E88Q mutations were detected in the primary and untreated metastatic tumor samples. Genes related to intracellular Ca2+ homeostasis were enriched among the genes uniquely mutated after FOLFOX chemotherapy.ConclusionsWe found that the mutation rates, mutation spectrum, and copy number variants were nearly identical regardless of the administration of FOLFOX therapy in the four CRC cases. The mutational discordance between the patient-matched tumor samples is likely caused by tumor heterogeneity and chemotherapy-induced clonal selection. These findings might be useful as pilot data for larger studies to clarify the changes in the mutational landscape induced by adjuvant FOLFOX chemotherapy.Electronic supplementary materialThe online version of this article (10.1186/s12885-019-5479-6) contains supplementary material, which is available to authorized users.

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“…Similarly, Li et al reported that advanced NSCLC patients with downregulation of APE1 , or TUBB3 protein benefited from platinum plus paclitaxel chemotherapy ( 33 ). In a study on unresectable locally advanced or metastatic NSCLC patients treated with cisplatin-based chemotherapy, patients with deficient expression of BRCA1 protein had a significantly higher survival rate than those with intact expression ( 34 ). A similar phenomenon was observed in our study cohort, where alteration of the BRCA1 gene was significantly associated with better clinical outcomes (data not shown).…”

Section: Discussionmentioning

confidence: 99%

“…The presence of DDR mutations has been reported to correlate with improved clinical outcomes in urothelial carcinoma (29), breast cancer (30), and prostate cancer (31). Previous studies have shown that downregulation of proteins of DDR pathways is associated with worse prognosis of stage I NSCLC patients having undergone surgery, as well as with increased efficacy of PC in locally advanced or metastatic NSCLC patients (32)(33)(34), but the correlation between DDR gene mutation and platinum chemotherapy efficacy in advanced NSCLC has not been verified in clinical studies. Similarly, although previous research has shown that DDR gene mutations are associated with immunotherapy efficacy in NSCLC (35), its correlation with IPC has not been reported.…”

Section: Introductionmentioning

confidence: 99%

DNA damage repair gene mutations predict the efficacy of platinum-based chemotherapy and immunotherapy plus platinum-based chemotherapy in advanced non-small cell lung cancer: a retrospective Chinese cohort study

Xiao¹,

Sun²,

Zheng³

et al. 2022

Transl Lung Cancer Res

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Background: Platinum-based chemotherapy (PC) and immunotherapy plus platinum-based chemotherapy (IPC) remain the first-line treatment for advanced NSCLC. But only a minority patients benefit from PC, and existing biomarkers, such as PD-L1, have been shown to be defective in predicting the efficacy of IPC.Highlighting the need to identify novel biomarkers for the efficacy of PC and IPC. DNA damage repair (DDR) mutations are known to predict response to PC in solid tumors. However, the predictive value of DDR in PC and IPC of NSCLC remains unclear.Methods: Patients diagnosed with advanced or metastatic NSCLC were retrospectively included if they underwent next generation sequencing prior to starting treatment. Primary endpoints were to explore whether DDR mutations (DDRmut) are associated with clinical outcomes of PC and IPC. Secondary end point were to explore the association between DDRmut and the choice to add immunotherapy to chemotherapy, and the impact of different DDR pathways on efficacy in PC and IPC.Results: DDRmut showed a strong association with tumor mutation burden-high (TMB-H) versus DDR wild-type (DDRwt) and higher rates of PD-L1 TPS ≥50% positivity. In 63 patients treated with PC, ORRs were 15.38% and 2.86% for DDRmut and DDRwt subgroup (P=0.1536), and DCRs were 88.46% and 45.72% (P=0.00097) at 6 months after PC. The DDRmut patients had significantly improved median PFS (mPFS) and median overall survival (mOS) than DDRwt group (mPFS: 7.6 vs. 3.9 months, HR =1.93, 95% CI: 1.09 to 3.14, P=0.0220. mOS: 29.9 vs. 20.7 months, HR =2.31, 95% CI: 1.09 to 4.9, P=0.0250). Moreover, among 37 patients treated with IPC, ORRs were 45% and 11.76% for DDRmut and DDRwt patients (P=0.0365), and the DCRs were 95% and 70.58% (P=0.0752), respectively at 6 months after IPC. The DDRmut patients had significantly improved mPFS compared to the DDRwt group (19.5 vs. 4.5 months, HR =3.28, 95% CI: 1.53 to 9.56, P=0.0022). In DDRmut group, mPFS of IPC recipients was significantly better than that of PC recipients (19.5 vs. 7.6 months, HR =2.09, 95% CI: 0.98 to 4.42, P=0.050). Conclusions:There is potential for DDR to serve as a positive predictor of PC and IPC in advanced NSCLC patients. Highlight box Key findings• DDR genes may be a positive predictor of platinum-based chemotherapy, and immunotherapy plus platinum-based chemotherapy in patients with advanced NSCLC. What is known and what is new?• DDR mutations are known to predict response to platinum-based chemotherapy in some solid tumors. • The predictive value of DDR mutations in platinum-based chemotherapy, and immunotherapy plus platinum-based chemotherapy of NSCLC. For patients with DDR mutations, median PFS receiving immunotherapy plus platinum-based chemotherapy was significantly better than those receiving platinum-based chemotherapy. What is the implication, and what should change now?• These results suggest that patients with DDR mutations can receive either platinum-based chemotherapy or immunotherapy plus platinum-based chemotherapy better than those with DDR wi...

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Correlation between BRCA1 and TopBP1 protein expression and clinical outcome of non-small cell lung cancer treated with platinum-based chemotherapy

Abstract: The present study indicates NSCLC patients with negative BRCA1 and TopBP1 expression showed better prognosis than those with positive protein expression.

Cited by 10 publications

References 19 publications

Pretreatment albumin/fibrinogen ratio as a promising predictor for the survival of advanced non small-cell lung cancer patients undergoing first-line platinum-based chemotherapy

Pretreatment albumin/fibrinogen ratio as a promising predictor for the survival of advanced non small-cell lung cancer patients undergoing first-line platinum-based chemotherapy

Comparative sequence analysis of patient-matched primary colorectal cancer, metastatic, and recurrent metastatic tumors after adjuvant FOLFOX chemotherapy

DNA damage repair gene mutations predict the efficacy of platinum-based chemotherapy and immunotherapy plus platinum-based chemotherapy in advanced non-small cell lung cancer: a retrospective Chinese cohort study

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