The Prognostic 97 Chemoresponse Gene Signature in Ovarian Cancer

Matondo, Abel; Jo, Yunhee; Shahid, Muhammad; Choi, Tae Gyu; Nguyen, Manh Tuan; Nguyen, Ngoc Ngo Yen; Akter, Salima; Kang, In‐Cheol; Ha, Joohun; Maeng, Chi Hoon; Kim, Sang Yong; Lee, Ju Seog; Kim, Jayoung; Kim, Sung Soo

doi:10.1038/s41598-017-08766-5

Cited by 29 publications

(35 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent study attempted to identify gene signatures predictive of high-risk and low-risk HGS-OvCas [ 87 , 88 ]. In this context, particularly interesting were the results of a study carried out by Matondo and coworkers, reporting the identification of a prognostic 97 chemoresponse gene signature in HGS-OvCa patients [ 88 ].…”

Section: Genetic Abnormalities Of Serous Ovarian Cancersmentioning

confidence: 99%

Ovarian Cancers: Genetic Abnormalities, Tumor Heterogeneity and Progression, Clonal Evolution and Cancer Stem Cells

et al. 2018

View full text Add to dashboard Cite

Four main histological subtypes of ovarian cancer exist: serous (the most frequent), endometrioid, mucinous and clear cell; in each subtype, low and high grade. The large majority of ovarian cancers are diagnosed as high-grade serous ovarian cancers (HGS-OvCas). TP53 is the most frequently mutated gene in HGS-OvCas; about 50% of these tumors displayed defective homologous recombination due to germline and somatic BRCA mutations, epigenetic inactivation of BRCA and abnormalities of DNA repair genes; somatic copy number alterations are frequent in these tumors and some of them are associated with prognosis; defective NOTCH, RAS/MEK, PI3K and FOXM1 pathway signaling is frequent. Other histological subtypes were characterized by a different mutational spectrum: LGS-OvCas have increased frequency of BRAF and RAS mutations; mucinous cancers have mutation in ARID1A, PIK3CA, PTEN, CTNNB1 and RAS. Intensive research was focused to characterize ovarian cancer stem cells, based on positivity for some markers, including CD133, CD44, CD117, CD24, EpCAM, LY6A, ALDH1. Ovarian cancer cells have an intrinsic plasticity, thus explaining that in a single tumor more than one cell subpopulation, may exhibit tumor-initiating capacity. The improvements in our understanding of the molecular and cellular basis of ovarian cancers should lead to more efficacious treatments.

show abstract

Section: Genetic Abnormalities Of Serous Ovarian Cancersmentioning

confidence: 99%

Ovarian Cancers: Genetic Abnormalities, Tumor Heterogeneity and Progression, Clonal Evolution and Cancer Stem Cells

et al. 2018

View full text Add to dashboard Cite

show abstract

“…First, most patients with ovarian cancer ultimately die of bowel obstruction caused by intraperitoneal disease, which was particularly the case in the predominantly peritoneal recurrence group (53%). Secondly, these tumors may differ in their genomic landscape, leading to differences in behavior [17][18][19][20]. Thirdly, patients with intraperitoneal recurrence may have had a higher tumor load at recurrence compared to patients with other recurrence patterns.…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of radiological recurrence patterns in ovarian cancer

Roze

Veldhuis

Hoogendam

et al. 2020

Gynecologic Oncology

View full text Add to dashboard Cite

• Radiologically assessed recurrence patterns can help to counsel patients on their prognosis at recurrence. • A predominantly lymphatic recurrence has a better survival than a predominantly peritoneal or hematogenous recurrence. • In patients with recurrent disease, the completeness of surgery is associated with the time to recurrence. • There are no differences in recurrence patterns between patients with complete and incomplete debulking surgery. • Linking the pattern of recurrence to survival outcomes could lead to differentiated treatment strategies.

show abstract

“…The median was subtracted from each gene individually. The Compound Covariate Predictor (CCP) was used as a class prediction algorithm to further refine this model and to sub-stratify outcome predictions [17, 19–21].…”

Section: Methodsmentioning

confidence: 99%

A Novel Melatonergic Signature Predicts Reccurence Risk and Therapeutic Response in Breast Cancer Patients

et al. 2018

Preprint

Self Cite

View full text Add to dashboard Cite

ASMT is a key determinant of the levels of released melatonin. Though melatonin has been shown to exhibit anti-cancer activity and prevents endocrine resistance in breast cancer, the role of ASMT in breast cancer progression remains unclear. In this retrospective study, we analyzed gene expression profiles from thousands of patients and found that ASMT expression was significantly lower in breast cancer tumors relative to healthy tissue. Among cancer patients, those with greater expression had better relapse-free survival outcomes and longer metastasisfree survival times, and they also experienced longer periods before relapse or distance recurrence following tamoxifen treatment. Administration of melatonin, in combination with tamoxifen, further promoted cancer cell death by promoting apoptosis. Motivated by these results, we devised an ASMT gene signature that identifies low-risk cases with great accuracy.This signature was validated using both mRNA array and RNAseq datasets. Intriguingly, patients who are classified as high-risk benefit from adjuvant chemotherapy, and those with grade II tumors who are classified as low-risk exhibit improved overall survival and distance relapse-free outcomes following endocrine therapy. Our findings more clearly elucidate the roles of ASMT, provide strategies for improving the efficacy of tamoxifen treatment, and help to identify those patients who may maximally benefit from adjuvant or endocrine therapies. in breast tumors, and elevated levels of ASMT expression improve relapse-free survival (RFS) outcomes and metastasis-free survival times. Relative to other breast cancer patients, those with relatively higher expression levels of ASMT exhibit fewer relapses or longer distance recurrence outcomes following tamoxifen treatment. Administration of melatonin, in combination with tamoxifen, further promotes cancer cell death by upregulating apoptosis. Furthermore, we also devise a novel gene signature that can robustly predict recurrence risk. Patients predicted to be high-risk benefitted significantly from adjuvant chemotherapy. In addition, following endocrine therapy, low-risk patients benefited from better overall survival and distance relapse-free outcomes. 5 Materials and methodsCell culture preparation MCF7 cells were grown to 70% confluence in phenol-red-free RPMI 1640 supplemented with 10% fetal bovine serum, 100 units/ml penicillin and 100 μ g/ml streptomycin sulfate at 37°C in a humidified 5% CO2 environment. Cells were pretreated with 1.0 mM melatonin for 2h then treated with 2.5 µM 4-OHT for 24h. Melatonin and 4-OHT were freshly prepared in a 1000X stock solution in DMSO and then diluted to the desired concentration directly in the culture medium. DMSO was added to control groups in each experiment. Live cells were observed under a Nikon Eclipse TE200 inverted microscope (Nikon, Tokyo, Japan). Cell apoptosis assaysThe apoptotic cell distribution was evaluated using the Muse Annexin V & Dead Cell Kit from Merck Millipore (Danvers, MA, USA) per the manufacturer's inst...

show abstract

The Prognostic 97 Chemoresponse Gene Signature in Ovarian Cancer

Cited by 29 publications

References 55 publications

Ovarian Cancers: Genetic Abnormalities, Tumor Heterogeneity and Progression, Clonal Evolution and Cancer Stem Cells

Ovarian Cancers: Genetic Abnormalities, Tumor Heterogeneity and Progression, Clonal Evolution and Cancer Stem Cells

Prognostic value of radiological recurrence patterns in ovarian cancer

A Novel Melatonergic Signature Predicts Reccurence Risk and Therapeutic Response in Breast Cancer Patients

Contact Info

Product

Resources

About