Abstract:
BACKGROUND:High amplification of epiregulin (EREG) and amphireglin (AREG) in tumour tissues has been previously reported to be associated with better outcome in metastatic colorectal cancer (mCRC) patients who were treated with anti-EGFR antibodies. Here we investigated associations between the expression of other candidate prognostic biomarkers and outcome in mCRC patients receiving similar treatment. METHODS:The relative mRNA levels of seven genes including ERBB2, MET, VEGFA, EREG, AREG, PTEN and ERCC1 between tumour (T) and non-tumour (NT) tissue sections were analysed by quantitative real-time PCR. Relative mRNA values, that is, T/NT ratios, of target genes were calculated and hazard ratios (HRs) for each gene of interest were adjusted for age, gender, performance status, minor RAS mutations and other clinicopathological variables which exhibited P-values<0.1 on the basis of univariate analysis. RESULTS:Among 108 cases who received anti-EGFR antibodies, there were 96 cases of KRAS exon2 wild-type patients enroled in this study. When the cutoff values for relative mRNA levels were set to the upper 25th percentile of all patients, there were statistically significant differences in overall survival (OS) between the patients with high and low levels of EREG (HR: 0.326, 95% CI: 0.136-0.772, P=0.011), ERBB2 (HR: 1.31, 95% CI: 1.084-1.652, P=0.040), MET (HR: 2.48, 95% CI: 1.356-5.463, P=0.026), and VEGF-A (HR: 1.29, 95% CI: 1.036-1.606, P=0.046). In addition, patients with high ERBB2 had shorter progression-free survival (PFS) compared with low ERBB2 (HR: 1.98, 95% CI: 1.062-3.850). There were no significant differences in PFS and OS with respect to relative expression levels of PTEN and ERCC1. The prognostic role of AREG was evaluated in only T sections, as the mRNA expression level of this gene was mostly (91% cases) undetectable in NT sections. Patients with high AREG had longer OS compared with low AREG (HR: 0.227, 95% CI: 0.095-0.808). CONCLUSIONS:Our study has shown that higher T/NT ratios of ERBB2, MET and VEGFA mRNA were associated with worse OS in mCRC patients treated with anti-EGFR antibodies, with higher EREG and AREG were associated with better prognosis in the same setting. These findings will contribute the further understanding and management of anti-EGFR antibody treatment in mCRC patients.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Takahashi N,Iwasa S,Taniguchi H,Sasaki Y,Shoji H,Honma Y,Takashima A,Okita N,Kato K,Hamaguchi T,Shimada Y,Yamada Ydoi
10.1038/bjc.2016.74subject
Has Abstractpub_date
2016-04-26 00:00:00pages
1003-11issue
9eissn
0007-0920issn
1532-1827pii
bjc201674journal_volume
114pub_type
杂志文章abstract::Doxorubicin- and paclitaxel-selected variants of an in vitro invasive clonal population of the human breast cancer cell line, MDA-MB-435S, were established by pulse selection, and exhibited a novel 'superinvasive' phenotype. This phenotype is characterised by an ability to relocate to another surface following invasio...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6602221
更新日期:2004-11-15 00:00:00
abstract::To identify tumour and tumour-associated antigens in patients with hepatocellular carcinoma (HCC) one may find potential diagnostic markers and immunotherapeutic targets. In the current study, 30 distinct antigens reactive with serum IgG from HCC patients were identified by serological analysis of cDNA expression libr...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6602460
更新日期:2005-03-14 00:00:00
abstract:BACKGROUND:To evaluate the prognostic value of lymph node density (LND) in patients with lymph node-positive cervical cancer. METHODS:A total of 88 consecutive patients were included in our study. Patients were treated with cisplatin-based concomitant chemoradiotherapy after surgical staging was performed at the Medic...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6605801
更新日期:2010-08-24 00:00:00
abstract::Counter-irritation (CI) triggered by different non-specific irritant stimuli delayed the growth of a murine tumour of non-detected immunogenicity. The syngeneic LB tumour transplant by itself also induced CI and decreased the number of leukocytes migrating to a secondary s.c. irritant stimulus, e.g. sponge or carragee...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1989.349
更新日期:1989-11-01 00:00:00
abstract::Phorbol-12-myristate-13-acetate (PMA) induces p21WAF-1 expression in human myeloid leukaemic HL-60 cells. We show that this induction is specifically mediated by protein kinase C (PKC). In addition, the PKC inhibitor Ro 31-8220 with predominant PKC-alpha isoform specificity almost completely inhibited PMA-induced up-r...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1997.595
更新日期:1997-01-01 00:00:00
abstract::The aim of this study was to assess the relationship between haemoglobin level and quality-of-life in anaemic cancer patients. Patients, diagnosed with one of four cancers, were recruited if their haemoglobin level was <12 g dl(-1) (female) or <13 g dl(-1) (male). The condition-specific Functional Assessment of Cancer...
journal_title:British journal of cancer
pub_type: 杂志文章,多中心研究
doi:10.1038/sj.bjc.6600247
更新日期:2002-04-22 00:00:00
abstract:BACKGROUND:Radio- and chemotherapy (RT/CT) resistance hampers success in combating small and non-small cell lung cancers (SCLC/NSCLC). The underlying molecular mechanisms of RT/CT resistance of LCs are multifactorial and have been understood in part hitherto. miRNAs, key regulators of mRNAs, are well-recognised oncomir...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2012.382
更新日期:2012-10-09 00:00:00
abstract::HER2/neu-derived peptides inducing MHC class II-restricted CD4+ T helper lymphocyte (Th) responses, although critical for tumour rejection, are not thoroughly characterized. Here, we report the generation and characterization of CD4+ T cell clones specifically recognizing a HER-2/neu-derived peptide (776-788) [designa...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1054/bjoc.2001.2089
更新日期:2001-11-16 00:00:00
abstract:BACKGROUND:Platinum-based doublet chemotherapy is the standard first-line treatment for advanced non-small cell lung cancer (NSCLC), but earlier studies have suggested that non-platinum combinations are equally effective and better tolerated. We conducted a national, randomised study to compare a non-platinum with a pl...
journal_title:British journal of cancer
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1038/bjc.2012.284
更新日期:2012-07-24 00:00:00
abstract:BACKGROUND:Although inequalities in cancer survival are thought to reflect inequalities in stage at diagnosis, little evidence exists about the size of potential survival gains from eliminating inequalities in stage at diagnosis. METHODS:We used data on patients diagnosed with malignant melanoma in the East of England...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2015.50
更新日期:2015-03-31 00:00:00
abstract::A correction to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title:British journal of cancer
pub_type: 已发布勘误
doi:10.1038/s41416-019-0505-7
更新日期:2019-07-01 00:00:00
abstract::An apparently unique circulating common oncofoetal protein has been identified in rat small-bowel, colonic and pancreatic adenocarcinomas. The tumours were induced by ionizing radiation (small bowel), an alkyl hydrocarbon, 1,2-dimethylhydrazine (colon) and a polyaromatic hydrocarbon, 7,12-dimethylbenz[a]anthracene (pa...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1981.120
更新日期:1981-06-01 00:00:00
abstract::We have previously reported that interleukin 10 (IL-10) signalling stimulated activation of a specific enhancer element, termed HTE-1, to promote tissue inhibitor of matrix metalloproteinase1 (TIMP-1) expression in human bone metastatic PC-3 subclone (PC-3 ML) cells. Recently, we have identified an IL-10 responsive si...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6600855
更新日期:2003-05-19 00:00:00
abstract::This study sought to use a microdialysis technique to relate clinical and biochemical responses to the time course of melphalan concentrations in the subcutaneous interstitial space and in tumour tissue (melanoma, malignant fibrous histiocytoma, Merkel cell tumour and osteosarcoma) in patients undergoing regional chem...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章
doi:10.1054/bjoc.2001.1902
更新日期:2001-07-20 00:00:00
abstract:METHODS:Maternally reported congenital abnormalities (CAs) were examined in a case-control study of 278 cases of paediatric germ cell tumours (GCTs) and 423 controls. RESULTS AND CONCLUSIONS:Germ cell tumours were significantly associated with cryptorchidism in males (OR=10.8, 95% CI: 2.1-55.1), but not with any other...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6605169
更新日期:2009-08-04 00:00:00
abstract::Several techniques are under development to diagnose oesophageal adenocarcinoma at an earlier stage. We have demonstrated the potential of Raman spectroscopy, an optical diagnostic technique, for the identification and classification of malignant changes. However, there is no clear recognition of the biochemical chang...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6603102
更新日期:2006-05-22 00:00:00
abstract::We examined bone marrow aspirates from 100 metastasis-free primary breast cancer patients. In 38/100 patients (38%), tumour cells were detected in the marrow using an immunocytochemical technique with a cocktail of two monoclonal antibodies: anti-EMA and anti-cytokeratin. Median follow-up was 34 months: 15/38 (39%) tu...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1994.103
更新日期:1994-03-01 00:00:00
abstract::Many theories mention hypersensitive, promiscuous, outlaw or bypass signalling pathways to explain the acquisition of hormone independence in prostate cancer. Hormonal escape of prostate tumours is marked by many biological changes, including mucinous and neuroendocrine differentiation. Since expression of several muc...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6601570
更新日期:2004-02-09 00:00:00
abstract:BACKGROUND:Epithelial-to-mesenchymal transition (EMT) is associated with decreased adhesion and acquisition of metastatic potential of breast cancer cells. Epithelial-to-mesenchymal transition is mediated, in part, by two transcription repressors, Snail and Slug, that are known to be targets of the Notch signaling path...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6605486
更新日期:2010-01-19 00:00:00
abstract::Solid tumour cells were shown to express VLA-beta and Thy-1 antigens. For identification of these molecules two monoclonal antibodies, K-20 and ICO-10, characterised in detail previously, were used. Four groups of solid tumours have been identified according to their immunophenotype: VLA-beta+ and Thy-1-; VLA-beta+ an...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1990.39
更新日期:1990-02-01 00:00:00
abstract::Postoperative hyperplasia enhances experimental intestinal carcinogenesis, but the effects of nonsurgical adaptation are uncertain. The tropic and tumour-promoting potentials of moderate hypothermia were tested in two groups of male Sprague-Dawley rats housed at 10 degrees C for 30 weeks. One group (n = 10) received a...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1987.51
更新日期:1987-03-01 00:00:00
abstract::The last 15 years has seen an explosion of interest in the cancer stem cell (CSC). Although it was initially believed that only a rare population of stem cells are able to undergo self-renewing divisions and differentiate to form all populations within a malignancy, a recent work has shown that these cells may not be ...
journal_title:British journal of cancer
pub_type: 杂志文章,评审
doi:10.1038/sj.bjc.6605821
更新日期:2010-08-10 00:00:00
abstract::Between 1980 and 1985, 914 patients with head and neck squamous cell carcinoma underwent lymph node dissection in our institution. The prognostic value of clinical factors has already been reported (Mamelle et al, 1994, Am J Surg 168: 494-498). We present here a comparison of biological characteristics of pharyngeal t...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1998.320
更新日期:1998-06-01 00:00:00
abstract::In the district of Srikakulam in Andhra Pradesh in South India the habit of reverse smoking is widespread. In a house to house survey of oral cancer and precancerous conditions, comprising 10,169 villagers, 43·8% were reverse smokers; the female: male ratio being 1·7: 1. Ten previously undiagnosed cases of oral cancer...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1971.2
更新日期:1971-03-01 00:00:00
abstract:BACKGROUND:This Phase Ib dose-escalating study investigated safety, maximum tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics (PK) and clinical antitumour activity of tosedostat (CHR-2797), an orally bioavailable aminopeptidase inhibitor, in combination with paclitaxel. METHODS:A total of 22 patient...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6605917
更新日期:2010-10-26 00:00:00
abstract:BACKGROUND:Doxorubicin and cyclophosphamide (AC) therapy is an effective treatment for early-stage breast cancer. Doxorubicin is a substrate for ABCB1 and SLC22A16 transporters. Cyclophosphamide is a prodrug that requires oxidation to 4-hydroxycyclophosphamide, which yields a cytotoxic alkylating agent. The initial oxi...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6605587
更新日期:2010-03-16 00:00:00
abstract::The multivariate lognormal survival model can be used to determine the relationship of prognostic covariates to two important parameters of malignancy. Cured fraction and median survival time among uncured patients. Analysis with this model revealed that cured fraction is primarily a function of histologic type and no...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1993.196
更新日期:1993-05-01 00:00:00
abstract:BACKGROUND:Late effects of cisplatin-based chemotherapy in testicular cancer survivors (TCS) include cardiovascular morbidity, but little data is available beyond 20 years. The objective was to assess vascular damage in very long-term TCS. METHODS:TCS (treated with chemotherapy or orchiectomy only) and age-matched hea...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/s41416-020-01049-3
更新日期:2020-11-01 00:00:00
abstract::The c-erbB-2 product is thought to be a unique and useful target for antibody therapy of cancers overexpressing the c-erbB-2 gene. In vitro and in vivo anti-tumour effects of a humanised antibody against the extracellular domain of the c-erbB-2 gene product, rhu4D5, were examined. Rhu4D5 was less effective than its mu...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1996.259
更新日期:1996-06-01 00:00:00
abstract:BACKGROUND:Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are commonly used antihypertensives. Recently, these drugs have been associated with a protective effect against pancreatic cancer, but data on this putative association remain limited. Thus, the objective of this study...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2016.375
更新日期:2017-01-03 00:00:00