CD44 Isoform Status Predicts Response to Treatment with Anti-CD44 Antibody in Cancer Patients

Abnormal long non-coding RNAs (lncRNAs) expression has been documented to have oncogene or tumor suppressor functions in the development and progression of cancer, emerging as promising independent biomarkers for molecular cancer stratification and patients’ prognosis. Examining the relationship between lncRNAs and the survival rates in malignancies creates new scenarios for precision medicine and targeted therapy. Breast cancer (BRCA) is a heterogeneous malignancy. Despite advances in its molecular classification, there are still gaps to explain in its multifaceted presentations and a substantial lack of biomarkers that can better predict patients’ prognosis in response to different therapeutic strategies. Here, we performed a re-analysis of gene expression data generated using cDNA microarrays in a previous study of our group, aiming to identify differentially expressed lncRNAs (DELncRNAs) with a potential predictive value for response to treatment with taxanes in breast cancer patients. Results revealed 157 DELncRNAs (90 up- and 67 down-regulated). We validated these new biomarkers as having prognostic and predictive value for breast cancer using in silico analysis in public databases. Data from TCGA showed that compared to normal tissue, MIAT was up-regulated, while KCNQ1OT1, LOC100270804, and FLJ10038 were down-regulated in breast tumor tissues. KCNQ1OT1, LOC100270804, and FLJ10038 median levels were found to be significantly higher in the luminal subtype. The ROC plotter platform results showed that reduced expression of these three DElncRNAs was associated with breast cancer patients who did not respond to taxane treatment. Kaplan–Meier survival analysis revealed that a lower expression of the selected lncRNAs was significantly associated with worse relapse-free survival (RFS) in breast cancer patients. Further validation of the expression of these DELncRNAs might be helpful to better tailor breast cancer prognosis and treatment.

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Evaluation of Prognostic and Predictive Significance of Circulating MicroRNAs in Ovarian Cancer Patients

Disease Markers ◽

10.1155/2017/3098542 ◽

2017 ◽

Vol 2017 ◽

pp. 1-9 ◽

Cited By ~ 22

Author(s):

Ann Rita Halvorsen ◽

Gunnar Kristensen ◽

Andy Embleton ◽

Cybil Adusei ◽

Maria Pilar Barretina-Ginesta ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Patients ◽

Prognostic Significance ◽

Response To Treatment ◽

Rank Test ◽

Specific Marker ◽

High Grade ◽

Standard Chemotherapy ◽

Validation Set ◽

Serous Tumors

Ovarian cancer patients are recognized with poor prognosis. This study aimed to identify microRNAs in plasma for predicting response to treatment and outcome. We have investigated microRNAs in plasma from ovarian cancer patients enrolled in a large multicenter study (ICON7), investigating the effect of adding bevacizumab to standard chemotherapy in patients diagnosed with epithelial ovarian cancer. Patients with different histology, grade, and FIGO stages were included (n=207) in this study. Screening of 754 unique microRNAs was performed in the discovery phase (n=91) using TaqMan Low Density Arrays. The results were validated using single assays and RT-qPCR. Low levels of miR-200b, miR-1274A (tRNALys5), and miR-141 were significantly associated with better survival, confirmed with log-rank test in the validation set. The level of miR-1274A (tRNALys5) correlated with outcome was especially pronounced in the high-grade serous tumors. Interestingly, low level of miR-200c was associated with 5-month prolongation of PFS when treated with bevacizumab compared to standard chemotherapy. We found prognostic significance of miR-200b, miR-141, and miR-1274A (tRNALys5) in all histological types, where miR-1274A (tRNALys5) may be a specific marker in high-grade serous tumors. The level of miR-200c may be predictive of effect of treatment with bevacizumab. However, this needs further validation.

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Impact of IGF-I and CYP19 Gene Polymorphisms on the Survival of Patients With Metastatic Prostate Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2005.02.9439 ◽

2006 ◽

Vol 24 (13) ◽

pp. 1982-1989 ◽

Cited By ~ 58

Author(s):

Norihiko Tsuchiya ◽

Lizhong Wang ◽

Hiroyoshi Suzuki ◽

Takehiko Segawa ◽

Hisami Fukuda ◽

...

Keyword(s):

Prostate Cancer ◽

Bone Metastasis ◽

Cancer Patients ◽

Genetic Polymorphisms ◽

Metastatic Prostate Cancer ◽

Genetic Factors ◽

Response To Treatment ◽

Logrank Test ◽

Ca Repeat ◽

Igf I

Purpose The prognosis of metastatic prostate cancer significantly differs among individuals. While various clinical and biochemical prognostic factors for survival have been suggested, the progression and response to treatment of those patients may also be defined by host genetic factors. In this study, we evaluated genetic polymorphisms as prognostic predictors of metastatic prostate cancer. Patients and Methods One hundred eleven prostate cancer patients with bone metastasis at the diagnosis were enrolled in this study. Thirteen genetic polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism or an automated sequencer with a genotyping software. Results Among the polymorphisms, the long allele (over 18 [CA] repeats) of insulin-like growth factor-I (IGF-I) and the long allele (over seven [TTTA] repeats) of cytochrome P450 (CYP) 19 were significantly associated with a worse cancer-specific survival (P = .016 and .025 by logrank test, respectively). The presence of the long allele of either the IGF-I or CYP19 polymorphisms was an independent risk factor for death (P = .019 or .026, respectively). Furthermore, the presence of the long allele of both the IGF-I and CYP19 polymorphisms was a stronger predictor for survival (P = .001). Conclusion The prognosis of metastatic prostate cancer patients is suggested to be influenced by intrinsic genetic factors. The IGF-I (CA) repeat and CYP19 (TTTA) repeat polymorphisms may be novel predictors in prostate cancer patients with bone metastasis at the diagnosis.

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Genotoxic and Cytotoxic Damage by Cyclophosphamide and Adriamycin as a Response to Treatment in Breast Cancer Patients: Pilot Study

Journal of Cancer Therapy ◽

10.4236/jct.2015.62018 ◽

2015 ◽

Vol 06 (02) ◽

pp. 163-168 ◽

Cited By ~ 1

Author(s):

Jimena Garibay-Garcia ◽

Fernando Mejia-Sanchez ◽

Eduardo Ramírez-San-Juan ◽

Miriam V. Flores-Merino ◽

Julieta Castillo-Cadena

Keyword(s):

Breast Cancer ◽

Pilot Study ◽

Cancer Patients ◽

Response To Treatment ◽

Breast Cancer Patients

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Abstract 504: Circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) are superior to CA 15-3 in predicting tumor burden, patients response to treatment and overall survival (OS) rates in metastatic breast cancer patients from Egypt

10.1158/1538-7445.am2016-504 ◽

2016 ◽

Author(s):

Abdel-Rahman N. Zekri ◽

Abeer A. Bahnassy

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Metastatic Breast Cancer ◽

Cancer Patients ◽

Metastatic Breast ◽

Circulating Tumor Dna ◽

Tumor Burden ◽

Response To Treatment ◽

Breast Cancer Patients ◽

Tumor Dna

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PS02.195: CIRCULATING TUMOUR DNA HAS UTILITY IN THE CLINICAL MANAGEMENT OF ESOPHAGEAL CANCER

Diseases of the Esophagus ◽

10.1093/dote/doy089.ps02.195 ◽

2018 ◽

Vol 31 (Supplement_1) ◽

pp. 177-177

Author(s):

Wayne Phillips ◽

Michael Yates ◽

Sarah-Jane Dawson ◽

Cuong Duong ◽

Nicholas Clemons

Keyword(s):

Esophageal Cancer ◽

Cancer Patients ◽

Advanced Disease ◽

Digital Pcr ◽

Targeted Sequencing ◽

Response To Treatment ◽

Plasma Dna ◽

Blood Samples ◽

Free Dna ◽

Circulating Tumour Dna

Abstract Background Cell-free DNA, a consequence of normal cell death and apoptosis, is found in the blood of all individuals. In cancer patients, a proportion of circulating cell free DNA will be derived from tumour cells, and is termed circulating tumour DNA (ctDNA).We have developed a blood-based ‘liquid biopsy’ to detect ctDNA in plasma of esophageal cancer patients. Methods Tumour, buffy-coat (germline) and plasma samples were obtained from 28 esophageal cancer patients at the time of diagnosis. Serial blood samples were collected from 8 patients. Somatic DNA mutations in 9 genes (TP53, ARID1A, SMAD4, CDKN2A, SMARCA4, NRG1, APC, PIK3CA and KRAS) were evaluated in tumour biopsies and plasma using targeted sequencing. Tumour specific mutations were confirmed by droplet digital PCR, which was used to track patient-specific ctDNA in plasma from serially collected blood samples. Results Somatic mutations in at least one of the targeted genes were detected in 19/28 (68%) tumour biopsies. The same mutations were detected in ctDNA from plasma in 9/19 (48%) patients. Additional mutations that were not detected in the tumour biopsies were detected in plasma DNA from 2 patients, highlighting the issues of intra-tumoural heterogeneity and sampling bias of tumour biopsies. ctDNA was more frequently detected in patients with advanced disease where it represented a greater proportion of the total cell-free plasma DNA than in patients with localised disease. In patients with serial samples, levels of ctDNA correlated with response to treatment, and rises in ctDNA could be detected prior to clinical evidence of relapse. Conclusion Detection of ctDNA using targeted sequencing and digital PCR is feasible in the majority of esophageal cancer patients, particularly those with advanced disease. Dynamic changes in ctDNA levels reflect response to treatment and disease relapse as determined by conventional clinical imaging. We conclude that ctDNA levels can provide supplemental evidence regarding disease staging, as well as prognostic and predictive information that can inform therapeutic pathway decisions in esophageal cancer patients. Disclosure All authors have declared no conflicts of interest.

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