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  • 1
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. e21616-e21616
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e21616-e21616
    Abstract: e21616 Background: In Chinese patients with lung adenocarcinoma, the positive rate of EGFR mutation was 40% - 50%, EGFR-TKIs therapy for lung cancer was also aimed at this part of patients. However, different EGFR mutation types have different therapeutic effects, this study focuses on different EGFR mutation types to divide the population of lung adenocarcinoma. Methods: We retrospectively reviewed gene test results of two hundred and sixty-two treatment-naïve adenocarcinoma patients. Tumor tissues (199, 76%), plasma (46, 17.5%) and other samples (17, 6.5%) were subject to next-generation sequencing using a 59-gene panel, which enables simultaneously assess SNV, Indel, rearrangements and CNV variations. Results: There were 174 females. These patients were divided into four groups, which 139 were EGFR L858R, 99 were EGFR exon 19 deletion, 7 were EGFR 20 ins and 17 were uncommon EGFR mutations, the co-mutation proportions with EGFR were 84.9% (118/139), 76.8% (76/99), 71.4% (5/7) and 94.1% (16/17) respectively. The mean numbers of co-mutation genes in L858R and exon 19 deletion were 4.173 and 3.258 (p 〈 0.05). TP53 mutation was detected in 14.3% (1/7) 20ins group, which had a significant difference to L858R (59.7%, 83/139) and uncommon mutation groups (70.6%, 12/17) (p 〈 0.05). Meanwhile, EGFR amplification proportion in L858R (18%, 25/139) and exon 19 deletion (6.1%, 6/99) were significantly different (p 〈 0.05). The actionable mutations associated with target therapy involved in multiple pathways, for example, the HRR pathway and cell cycle pathway, related genes had no significant difference among the four groups. In these lung adenocarcinoma patients, we also found 6 EGFR T790M (2.3%, 6/262). Three cases accompanied with exon 19 deletion, and another three were L858R, no distribution in 20ins and uncommon groups. Conclusions: The phenomenon of concurrent gene mutation in treatment-naïve EGFR-mutant lung adenocarcinoma is common. EGFR mutant subgroups have different co-mutation features, like gene number and mutated genes. It may be the factor leading to different therapeutic effects of EGFR-TKIs, and indicate the importance of multiplex molecular test and further researches of target therapies.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 2
    In: BMC Cancer, Springer Science and Business Media LLC, Vol. 21, No. 1 ( 2021-12)
    Abstract: EGFR and ALK alternations often contribute to human malignancies, including lung cancer. EGFR and ALK mutations are usually sensitive to EGFR-tyrosine kinase inhibitors (TKIs) and ALK-TKIs. Although generally mutually exclusive, these mutations do co-exist in rare cases. This study investigated the frequencies, clinical characteristics, therapeutic efficacies, and genetic profiles of lung cancer patients with EGFR and ALK co-mutations. Methods Patients with concurrent EGFR and ALK mutations were included in this study, which analyzed mutation profiles and treatment histories. SPSS20.0 were used for survival analysis. Results Among 271 ALK-positive (ALK-pos) and 2975 EGFR-positive (EGFR-pos) patients in our database, nine (2.6% of ALK-pos and 0.2% of EGFR-pos) patients had concurrent EGFR and ALK mutations (including three exon19 Indel + EML4-ALK, two exon19 Indel + STRN-ALK, two L858R + L1152R, one L858R + EML4-ALK, and one G719C + S768I + STRN-ALK). Eight patients had at least one type of EGFR-TKIs treatment. The median progression free survival (PFS) of these patients on first-generation EGFR-TKIs was 14.5 months (95% CI: 11 - NR). Of these eight patients, one who progressed on Gefitinib and subsequently on Osimertinib had a T790M + C797G. The other seven EGFR-TKIs resistance patients had no known resistance mutations. No patients had ALK mutations before treatment, so ALK mutations may have developed as resistance mechanisms during EGFR-TKIs therapies. EGFR-TKIs-treated patients with EGFR/ALK L1152R mutations generally had a shorter PFS than patients with other mutation combinations. Conclusions ALK and EGFR mutations coincide at a relatively low frequency in lung cancer patients. ALK mutations developed either synchronously or heterochronously with EGFR mutations. Two ALK mutations (L1152R and STRN-ALK) may co-exist with EGFR mutations at a higher frequency than others. Most EGFR/ALK co-alteration patients (other than the EGFR/ALK L1152R type) can benefit from first line EGFR-TKIs.
    Type of Medium: Online Resource
    ISSN: 1471-2407
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2041352-X
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  • 3
    In: BMC Cancer, Springer Science and Business Media LLC, Vol. 23, No. 1 ( 2023-01-31)
    Abstract: Early diagnosis of lung adenocarcinoma (LUAD), one of the most common types of lung cancer, is very important to improve the prognosis of patients. The current methods can’t meet the requirements of early diagnosis. There is a pressing need to identify novel diagnostic biomarkers. Secretory proteins are the richest source for biomarker research. This study aimed to identify candidate secretory protein biomarkers for early diagnosis of LUAD by integrated bioinformatics analysis and clinical validation. Methods Differentially expressed genes (DEGs) of GSE31210, gene expression data of early stage of LUAD, were analyzed by GEO2R. Upregulated DEGs predicted to encode secreted proteins were obtained by taking the intersection of the DEGs list with the list of genes encoding secreted proteins predicted by the majority decision-based method (MDSEC). The expressions of the identified secreted proteins in the lung tissues of early-stage LUAD patients were further compared with the healthy control group in mRNA and protein levels by using the UALCAN database (TCGA and CPTAC). The selected proteins expressed in plasma were further validated by using Luminex technology. The diagnostic value of the screened proteins was evaluated by receiver operating characteristic (ROC) analysis. Cell counting kit-8 assay was carried out to investigate the proliferative effects of these screened proteins. Results A total of 2183 DEGs, including 1240 downregulated genes and 943 upregulated genes, were identified in the GSE31210. Of the upregulated genes, 199 genes were predicted to encode secreted proteins. After analysis using the UALCAN database, 16 molecules were selected for further clinical validation. Plasma concentrations of three proteins, Midkine (MDK), WAP four-disulfide core domain 2 (WFDC2), and C-X-C motif chemokine ligand 14 (CXCL14), were significantly higher in LUAD patients than in healthy donors. The area under the curve values was 0.944, 0.881, and 0.809 for MDK, WFDC2, and CXCL14, 0.962 when combined them. Overexpression of the three proteins enhanced the proliferation activity of A549 cells. Conclusions MDK, WFDC2, and CXCL14 were identified as candidate diagnostic biomarkers for early-stage LUAD and might also play vital roles in tumorigenesis.
    Type of Medium: Online Resource
    ISSN: 1471-2407
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2041352-X
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  • 4
    In: Journal of Clinical Pathology, BMJ
    Abstract: A new molecular subtype classification was proposed for small-cell lung carcinoma (SCLC). We aimed to further validate the classification in various SCLC patient samples using immunohistochemistry (IHC) to highlight its clinical significance. Methods We analysed the protein expression of four subtype (achaete-scute family BHLH transcription factor 1 (ASCL1), neuronal differentiation 1 (NEUROD1), POU class 2 homeobox 3 (POU2F3) and Yes1-associated transcriptional regulator (YAP1)) and two predictive markers (delta-like ligand 3 (DLL3) and MYC) using IHC in 216 specimens from 195 SCLC patients, including 21 pairs of resected biopsy tumours. Associations among molecular subtypes, clinicopathological features and prognostic implications were also explored. Results The ASCL1, NEUROD1, POU2F3, YAP1, DLL3 and MYC-positive expression rates were 70.3%, 56.9%, 14.9%, 19.0%, 75.4% and 22.6%, respectively. DLL3 expression had positive and negative associations with that of ASCL1 and POU2F3/YAP1, respectively, whereas MYC had the opposite effect. Strong associations of ASCL1 (Ρ=0.8603, p 〈 0.0001), NEUROD1 (Ρ=0.8326, p 〈 0.0001), POU2F3 (Ρ=0.6950, p 〈 0.0001) and YAP1 (Ρ=0.7466, p 〈 0.0001) expressions were detected between paired resected biopsy tumours. In addition to SCLC-A (ASCL1-dominant), SCLC-N (NEUROD1-dominant) and SCLC-P (POU2F3-dominant), unsupervised hierarchical cluster analyses identified a fourth, quadruple-negative SCLC subtype (SCLC-QN) characterised by the low expression of all four subtype-specific proteins, and 55.4% (n=108), 27.2% (n=53), 11.8% (n=23) and 5.6% (n=11) were categorised as SCLC-A, SCLC-N, SCLC-P and SCLC-QN, respectively. Significant enrichment of SCLC-P in the combined SCLC cohort was observed, and adenocarcinoma was more prevalent in SCLC-A, while large-cell neuroendocrine carcinoma was more commonly seen in SCLC-P. No survival difference was found among molecular subtypes. Conclusions Our results provide clinical insights into the diagnostic, prognostic and predictive significance of SCLC molecular subtype classifications.
    Type of Medium: Online Resource
    ISSN: 0021-9746 , 1472-4146
    RVK:
    Language: English
    Publisher: BMJ
    Publication Date: 2023
    detail.hit.zdb_id: 2028928-5
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  • 5
    Online Resource
    Online Resource
    Frontiers Media SA ; 2020
    In:  Frontiers in Oncology Vol. 10 ( 2020-4-24)
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 10 ( 2020-4-24)
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2020
    detail.hit.zdb_id: 2649216-7
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  • 6
    In: Oncology, S. Karger AG, Vol. 83, No. 5 ( 2012), p. 248-256
    Abstract: 〈 b 〉 〈 i 〉 Objective: 〈 /i 〉 〈 /b 〉 To identify the clinicopathological characteristics and clinical outcomes of Chinese patients with non-small cell lung cancer (NSCLC) and to investigate possible associations of NSCLC with echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) and epidermal growth factor receptor (EGFR) mutations. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 Patients with stage IV NSCLC were screened for EML4-ALK rearrangement and EGFR mutations at the Peking University Cancer Hospital. EML4-ALK was identified using fluorescent in situ hybridization and confirmed by immunohistochemistry. EGFR mutations were determined using denaturing high-performance liquid chromatography. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 The incidence of EML4-ALK was 9.7% (11/113). Patients with EML4-ALK were more likely to present the EGFR wild type (WT; p = 0.033). Response to EGFR-tyrosine kinase inhibitor (TKI) was similar between patients with EML4-ALK rearrangement and EGFR mutation (33.3 vs. 46.9%, p = 0.451), but progression-free survival (PFS) was inferior compared to those with EGFR mutation (2.1 vs. 8.8 months, p = 0.032), and similar to patients with WT/nonrearrangement (2.1 vs. 2.2 months, p = 0.696; and general p = 0.023 between the three cohorts). Moreover, 2 patients with concurrent EML4-ALK and EGFR mutations had superior PFS after EGFR-TKI compared to patients with single EML4-ALK rearrangement. 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 Patients with EML4-ALK conferred similar objective response rates after EGFR-TKI although inferior PFS compared to those with EGFR mutation. Coexistence of EML4-ALK and EGFR mutation might represent a separate NSCLC genotype.
    Type of Medium: Online Resource
    ISSN: 0030-2414 , 1423-0232
    RVK:
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2012
    detail.hit.zdb_id: 1483096-6
    detail.hit.zdb_id: 250101-6
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  • 7
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 15_suppl ( 2013-05-20), p. e19061-e19061
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. e19061-e19061
    Abstract: e19061^ Background: Retreatment of pemetrexed based chemotherapy (PBC) has been reported in MPM previously, but it is not investigated in non-squamous NSCLC (NS-NSCLC). Methods: We retrospectively enrolled 26 advanced NS-NSCLC patients who had received retreatment of PBC when their response to initial PBC were PR or SD. Chemotherapy regimens administered as retreatment were single pemetrexed (500 mg/m 2 every 3 weeks) or pemetrexed with a platinum. Response was evaluated according to RECIST. Toxicity was evaluated according to NCI-CTC version 3.0. PFS and OS were computed by Kaplan-Meier. Statistical analyses were performed with SPSS13.0. Results: In retreatment, most adverse effects (AE) were tolerable but doublet regimen was associated with higher AE including bone marrow depression and fatigue. In patients who received retreatment of PBC, objective response rate (ORR) and disease control rate (DCR) was 12% (3/26) and 73% (19/26) respectively. Patient with PFS≥10 months in initial PBC therapy would have a longer PFS in retreatment comparing with those PFS 〈 10 months (6.0 vs 3.1 month, p = 0.004); patients with therapy-free interval (TFI) ≥6 months after initial PBC therapy also have a longer PFS in retreatment comparing with those interval 〈 6 months (7.0 vs 3.0 month, p = 0.001). The OS also tend to be longer but not reach statistic significance. The response of first round PBC therapy (PR vs. SD) was not a factor affecting the PFS in retreatment. Conclusions: Patients with PFS over 10 months or TFI over 6 months after first round of PBC could benefit from retreatment of PBC.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
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  • 8
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. e19091-e19091
    Abstract: e19091 Background: To investigate predicting significance of EGFR mutations existing in tissues couples with plasma or either sample alone to EGFR–tyrosine kinase inhibitors (EGFR-TKIs) treatment for advanced non–small-cell lung cancer (A-NSCLC). Methods: Two hundred-eighty-seven A-NSCLC patients met following criteria were included into this study: 1) had received EGFR-TKIs as first- or second-line therapy; 2) had sufficient tissue and plasma samples for EGFR mutation analysis. All patients were divided into four subgroups which were wild-type EGFR in both of specimens (B - /T - ), mutated in both of specimens (B + /T + ), mutated only in one specimen (B + /T - and B - /T + ). EGFR mutation was screened by denaturing high performance liquid chromatograph (DHPLC) and confirmed by ARMS. Objective response rate (ORR) and progression-free survival (PFS) were compared among four subgroups. Results: Of all 287 patients, 101 patients carried EGFR mutation both in tissue and plasma, 103 patients carried mutation only in tissue (65 cases) or plasma (38 cases). Median PFS was 9.2 months (95% CI, 6.3 to 12.1) and 2.0 months (95% CI, 1.3 to 2.7) in B+/T+ and B-/T- group, respectively. For single mutated group, mPFS were 7.87 month for B-/T+ group (95% CI, 5.1 to 10.6) and 11.87 months for B+/T- group (95% CI, 3.3 to 20.5) (P=0.001). For ORR, 53.0% for B+/T+ group, 15.8% for B-/T- group, 40.0% for B-/T+ group and 28.9% for B+/T- group (P=0.000). EGFR-TKIs therapeutic line could not change trend which B+/T- or B+/T+ group had better PFS than B-/T+ group. Conclusions: Detection of EGFR mutation in tissue and plasma may have different significance in predicting response of EGFR-TKIs.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
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  • 9
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 15_suppl ( 2013-05-20), p. e19101-e19101
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. e19101-e19101
    Abstract: e19101 Background: Approximately 50% of advanced non-small cell lung cancer (A-NSCLC) patients with EGFR sensitive mutation who develop acquired resistance to EGFR-TKIs reportedly have a secondary EGFR T790M mutation. Establishing a dynamical, quantitative and noninvasive detection system of EGFR T790M mutation in process of disease therapy for NSCLC is critical to personalized targeted therapy. Methods: 135 A-NSCLC patients with EGFR mutation who received EGFR-TKIs and presented acquired resistance (PFS≥6 months) were included into this study. All patients provided the plasma samples for molecular analysis when disease progressed. 109 patients of them had matched TKI-naive plasma. T790M mutation was measured qualitatively and quantitatively by ARMS and Digital PCR (DggPCR), respectively. Association of T790M mutation with clinical charateristics were evaluated. Results: DgPCR was more sensitive than ARMs to detect T790M mutation in plasma [pre-treatment 29.4% (32/109) VS 5.5% (6/109); post-treatment: 43.0% (58/135) VS 25.2% (34/135)]. 32 patients with pre-treatment T790M mutation predicted shorter PFS and OS compared with 77 T790 M negative patients (PFS, F 12.7 VS 9.2 months, P=0.004, GOS, F 27.0 VS 18.8 months, P=0.002). Patients with or without post-treatment T790M mutation have no significantly different PFS and OS. However, quantified the ratio of copy number of mutant T790M to wild-type by DgPCR, patients were divided into high-frequency groups (≥5%), low-frequency group (0%-5%) and wild-group (0%) according to the number of positive signals observed from DgPCR results. 12 patients in high-frequency group showed shorter PFS and OS compared with wild group and low-frequency group (PFS 9.5 VS 11.9 months, P=0.033, G9.5 VS 13.6 months, P=0.028, GOS, F 18.5 VS 21.2 months, P=0.044, 18.5 VS 28.8 months, P=0.001). Conclusions: Non-invisive and quantitative detection of T790m mutation by digital PCR is feasible in clinical practice. High contents of T790M when disease progression after EGFR-TKIs therapy predicted poor prognosis.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
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  • 10
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2012
    In:  Journal of Clinical Oncology Vol. 30, No. 15_suppl ( 2012-05-20), p. e18035-e18035
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. e18035-e18035
    Abstract: e18035 Background: EML4-ALK rearrangement defines a new molecular subtype of non-small-cell lung cancer (NSCLC). To identify the biological profiles of these patients, we examined the clinico-pathologic characteristics and treatment outcomes of NSCLC patients based on EML4-ALK and EGFR mutations. Methods: Patients with stage IV NSCLC were screened for EML4-ALK rearrangement and EGFR mutations at Peking University Cancer Hospital. EML4-ALK was identified using fluorescent in situ hybridization (FISH) confirmed by immunohistochemistry (IHC), and EGFR mutations were determined using denaturing high-performance liquid chromatography (DHPLC). Results: Of the 151 patients screened, 113 had complete follow-up data as an analysis set. The incidence of EML4-ALK was 9.7% (11/113) using FISH, in which 10 cases had sufficient specimens for IHC confirmation and all were positive. Overall, EML4-ALK and EGFR mutations were largely mutually exclusive (p = 0.033), although two patients harbored concurrent mutations. EML4-ALK rearrangement was associated with resistance to EGFR-TKIs compared with the EGFR mutant type and WT/Nonrearrangement type (p = 0.001 for objective response rate; p = 0.004 for disease control rate; p = 0.021 for progression-free survival [PFS]). In terms of patients who received platinum-based doublet chemotherapy, no significant differences were observed in PFS between the EML4-ALK type, EGFR mutant type, and WT/Nonrearrangement type. Moreover, two patients with concurrent EML4-ALK and EGFR mutations had superior PFS after EGFR-TKI compared with single EML4-ALK-rearranged patients. Conclusions: This study presents several biological features of EML4-ALK NSCLC. It is largely mutually exclusive to EGFR mutations, resistant to EGFR-TKI. Coexistence of ALK rearrangement and EGFR mutation in patients with advanced NSCLC might represent a separate genotype with unique biological characteristics.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
    detail.hit.zdb_id: 2005181-5
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