Discovery of candidate tumor biomarkers for treatment with intraperitoneal chemotherapy for ovarian cancer

Brandon Luke L. Seagle; Kevin H. Eng; Judy Y. Yeh; Monica Dandapani; Emily Schiller; Robert Samuelson; Kunle Odunsi; Shohreh Shahabi

doi:10.1038/srep21591

Discovery of candidate tumor biomarkers for treatment with intraperitoneal chemotherapy for ovarian cancer

Brandon Luke L. Seagle, Kevin H. Eng, Judy Y. Yeh, Monica Dandapani, Emily Schiller, Robert Samuelson, Kunle Odunsi, Shohreh Shahabi^*

^*Corresponding author for this work

Medical Social Sciences

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Abstract

Tumor mRNA expression was used to discover genes associated with worse survival or no survival benefit after intraperitoneal (IP) chemotherapy. Data for high grade serous ovarian cancer patients treated with IP (n = 90) or IV-only (n = 398) chemotherapy was obtained from The Cancer Genome Atlas. Progression free survival (PFS) and overall survival (OS) were compared between IP and IV groups using Kaplan-Meier analysis and Cox regression. Validations were performed by analyses of microarray and RNA-Seq mRNA expression data. PFS and OS were compared between IP and IV groups by permutation testing stratified by gene expression. P-values are two-tailed. IP chemotherapy increased PFS (26.7 vs 16.0 months, HR 0.43 (0.28-0.66), p = 0.0001) and OS (49.6 vs 38.2 months, HR 0.46 (0.25-0.83), p = 0.01). Increased expression of NCAM2 and TSHR and decreased expression of GCNT1 was associated with decreased PFS and OS after IV chemotherapy (p < 0.05). High tumor expression of LMAN2, FZD4, FZD5, or STT3A was associated with no significant PFS increase after IP compared to IV chemotherapy. Low expression of APC2 and high expression of FUT9 was associated with 5.5 and 7.2 months, respectively, decreased OS after IP compared to IV chemotherapy (p ≤ 0.007).

Original language	English (US)
Article number	21591
Journal	Scientific reports
Volume	6
DOIs	https://doi.org/10.1038/srep21591
State	Published - Feb 17 2016

Funding

The results published here are based upon data generated by the TCGA Research Network: http://cancergenome. nih.gov/. This study was supported by by the Roswell Park Cancer Institute Alliance Foundation Award (KO), National Cancer Institute Cancer Center Support Grant NIH 2P30 CA016056-36 (KO), NIH 1R01CA158318-01A1 (KO), RPCI-UPCI Ovarian Cancer SPORE NIH P50CA159981-01A1 (KO), NIH K01LM012100 (KE), and NIH P30CA016056 (RPCI).

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@article{95276a011be1497bb89a42c8625f4f22,

title = "Discovery of candidate tumor biomarkers for treatment with intraperitoneal chemotherapy for ovarian cancer",

abstract = "Tumor mRNA expression was used to discover genes associated with worse survival or no survival benefit after intraperitoneal (IP) chemotherapy. Data for high grade serous ovarian cancer patients treated with IP (n = 90) or IV-only (n = 398) chemotherapy was obtained from The Cancer Genome Atlas. Progression free survival (PFS) and overall survival (OS) were compared between IP and IV groups using Kaplan-Meier analysis and Cox regression. Validations were performed by analyses of microarray and RNA-Seq mRNA expression data. PFS and OS were compared between IP and IV groups by permutation testing stratified by gene expression. P-values are two-tailed. IP chemotherapy increased PFS (26.7 vs 16.0 months, HR 0.43 (0.28-0.66), p = 0.0001) and OS (49.6 vs 38.2 months, HR 0.46 (0.25-0.83), p = 0.01). Increased expression of NCAM2 and TSHR and decreased expression of GCNT1 was associated with decreased PFS and OS after IV chemotherapy (p < 0.05). High tumor expression of LMAN2, FZD4, FZD5, or STT3A was associated with no significant PFS increase after IP compared to IV chemotherapy. Low expression of APC2 and high expression of FUT9 was associated with 5.5 and 7.2 months, respectively, decreased OS after IP compared to IV chemotherapy (p ≤ 0.007).",

author = "Seagle, {Brandon Luke L.} and Eng, {Kevin H.} and Yeh, {Judy Y.} and Monica Dandapani and Emily Schiller and Robert Samuelson and Kunle Odunsi and Shohreh Shahabi",

note = "Funding Information: The results published here are based upon data generated by the TCGA Research Network: http://cancergenome. nih.gov/. This study was supported by by the Roswell Park Cancer Institute Alliance Foundation Award (KO), National Cancer Institute Cancer Center Support Grant NIH 2P30 CA016056-36 (KO), NIH 1R01CA158318-01A1 (KO), RPCI-UPCI Ovarian Cancer SPORE NIH P50CA159981-01A1 (KO), NIH K01LM012100 (KE), and NIH P30CA016056 (RPCI).",

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AU - Samuelson, Robert

AU - Odunsi, Kunle

AU - Shahabi, Shohreh

N1 - Funding Information: The results published here are based upon data generated by the TCGA Research Network: http://cancergenome. nih.gov/. This study was supported by by the Roswell Park Cancer Institute Alliance Foundation Award (KO), National Cancer Institute Cancer Center Support Grant NIH 2P30 CA016056-36 (KO), NIH 1R01CA158318-01A1 (KO), RPCI-UPCI Ovarian Cancer SPORE NIH P50CA159981-01A1 (KO), NIH K01LM012100 (KE), and NIH P30CA016056 (RPCI).

PY - 2016/2/17

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N2 - Tumor mRNA expression was used to discover genes associated with worse survival or no survival benefit after intraperitoneal (IP) chemotherapy. Data for high grade serous ovarian cancer patients treated with IP (n = 90) or IV-only (n = 398) chemotherapy was obtained from The Cancer Genome Atlas. Progression free survival (PFS) and overall survival (OS) were compared between IP and IV groups using Kaplan-Meier analysis and Cox regression. Validations were performed by analyses of microarray and RNA-Seq mRNA expression data. PFS and OS were compared between IP and IV groups by permutation testing stratified by gene expression. P-values are two-tailed. IP chemotherapy increased PFS (26.7 vs 16.0 months, HR 0.43 (0.28-0.66), p = 0.0001) and OS (49.6 vs 38.2 months, HR 0.46 (0.25-0.83), p = 0.01). Increased expression of NCAM2 and TSHR and decreased expression of GCNT1 was associated with decreased PFS and OS after IV chemotherapy (p < 0.05). High tumor expression of LMAN2, FZD4, FZD5, or STT3A was associated with no significant PFS increase after IP compared to IV chemotherapy. Low expression of APC2 and high expression of FUT9 was associated with 5.5 and 7.2 months, respectively, decreased OS after IP compared to IV chemotherapy (p ≤ 0.007).

AB - Tumor mRNA expression was used to discover genes associated with worse survival or no survival benefit after intraperitoneal (IP) chemotherapy. Data for high grade serous ovarian cancer patients treated with IP (n = 90) or IV-only (n = 398) chemotherapy was obtained from The Cancer Genome Atlas. Progression free survival (PFS) and overall survival (OS) were compared between IP and IV groups using Kaplan-Meier analysis and Cox regression. Validations were performed by analyses of microarray and RNA-Seq mRNA expression data. PFS and OS were compared between IP and IV groups by permutation testing stratified by gene expression. P-values are two-tailed. IP chemotherapy increased PFS (26.7 vs 16.0 months, HR 0.43 (0.28-0.66), p = 0.0001) and OS (49.6 vs 38.2 months, HR 0.46 (0.25-0.83), p = 0.01). Increased expression of NCAM2 and TSHR and decreased expression of GCNT1 was associated with decreased PFS and OS after IV chemotherapy (p < 0.05). High tumor expression of LMAN2, FZD4, FZD5, or STT3A was associated with no significant PFS increase after IP compared to IV chemotherapy. Low expression of APC2 and high expression of FUT9 was associated with 5.5 and 7.2 months, respectively, decreased OS after IP compared to IV chemotherapy (p ≤ 0.007).

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Discovery of candidate tumor biomarkers for treatment with intraperitoneal chemotherapy for ovarian cancer

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