MiRNA predictors of pancreatic cancer chemotherapeutic response

A systematic review and meta-analysis

Madhav Madurantakam Royam, Rithika Ramesh, Ritika Shanker, Shanthi Sabarimurugan, Chellan Kumarasamy, Nachimuthu Ramesh, Kodiveri Muthukalianan Gothandam, Siddharta Baxi, Ajay Gupta, Sunil Krishnan, Rama Jayaraj

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Abstract

Background: Pancreatic cancer (PC) has increasing incidence and mortality in developing countries, and drug resistance is a significant hindrance to the efficacy of successful treatment. The objective of this systematic review and meta-analysis was to evaluate the association between miRNAs and response to chemotherapy in pancreatic cancer patients.

Methods: The systematic review and meta-analysis was based on articles collected from a thorough search of PubMed and Science Direct databases for publications spanning from January 2008 to December 2018. The articles were screened via a set of inclusion and exclusion criteria based on the preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines. Data was extracted, collated and tabulated in MS Excel for further synthesis. Hazard ratio (HR) was selected as the effect size metric to be pooled across studies for the meta-analysis, with the random effects model being applied. Subgroup analysis was also conducted, and the presence of publication bias in the selected studies was assessed. Publication bias of the included studies was quantified.

Findings: Of the 169 articles screened, 43 studies were included in our systematic review and 13 articles were included in the meta-analysis. Gemcitabine was observed to be the principal drug used in a majority of the studies. A total of 48 miRNAs have been studied, and 18 were observed to have possible contributions to chemoresistance, while 15 were observed to have possible contributions to chemosensitivity. 41 drug-related genetic pathways have been identified, through which the highlighted miRNA may be affecting chemosensitivity/resistance. The pooled HR value for overall survival was 1.603; (95% Confidence Interval (CI) 1.2–2.143; p-value: 0.01), with the subgroup analysis for miR-21 showing HR for resistance of 2.061; 95% CI 1.195–3.556; p-value: 0.09. Interpretation: Our results highlight multiple miRNAs that have possible associations with modulation of chemotherapy response in pancreatic cancer patients. Further studies are needed to di scover the molecular mechanisms underlying these associations before they can be suggested for use as biomarkers of response to chemotherapeutic interventions in pancreatic cancer.

Original languageEnglish
Article number900
Pages (from-to)1-25
Number of pages25
JournalCancers
Volume11
Issue number7
Early online date27 Jun 2019
DOIs
Publication statusPublished - 1 Jul 2019

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Pancreatic Neoplasms
Meta-Analysis
MicroRNAs
Publication Bias
gemcitabine
Confidence Intervals
Drug Therapy
Drug Resistance
PubMed
Pharmaceutical Preparations
Developing Countries
Publications
Biomarkers
Databases
Guidelines
Survival
Mortality
Incidence

Cite this

Royam, M. M., Ramesh, R., Shanker, R., Sabarimurugan, S., Kumarasamy, C., Ramesh, N., ... Jayaraj, R. (2019). MiRNA predictors of pancreatic cancer chemotherapeutic response: A systematic review and meta-analysis. Cancers, 11(7), 1-25. [900]. https://doi.org/10.3390/cancers11070900
Royam, Madhav Madurantakam ; Ramesh, Rithika ; Shanker, Ritika ; Sabarimurugan, Shanthi ; Kumarasamy, Chellan ; Ramesh, Nachimuthu ; Gothandam, Kodiveri Muthukalianan ; Baxi, Siddharta ; Gupta, Ajay ; Krishnan, Sunil ; Jayaraj, Rama. / MiRNA predictors of pancreatic cancer chemotherapeutic response : A systematic review and meta-analysis. In: Cancers. 2019 ; Vol. 11, No. 7. pp. 1-25.
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abstract = "Background: Pancreatic cancer (PC) has increasing incidence and mortality in developing countries, and drug resistance is a significant hindrance to the efficacy of successful treatment. The objective of this systematic review and meta-analysis was to evaluate the association between miRNAs and response to chemotherapy in pancreatic cancer patients. Methods: The systematic review and meta-analysis was based on articles collected from a thorough search of PubMed and Science Direct databases for publications spanning from January 2008 to December 2018. The articles were screened via a set of inclusion and exclusion criteria based on the preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines. Data was extracted, collated and tabulated in MS Excel for further synthesis. Hazard ratio (HR) was selected as the effect size metric to be pooled across studies for the meta-analysis, with the random effects model being applied. Subgroup analysis was also conducted, and the presence of publication bias in the selected studies was assessed. Publication bias of the included studies was quantified. Findings: Of the 169 articles screened, 43 studies were included in our systematic review and 13 articles were included in the meta-analysis. Gemcitabine was observed to be the principal drug used in a majority of the studies. A total of 48 miRNAs have been studied, and 18 were observed to have possible contributions to chemoresistance, while 15 were observed to have possible contributions to chemosensitivity. 41 drug-related genetic pathways have been identified, through which the highlighted miRNA may be affecting chemosensitivity/resistance. The pooled HR value for overall survival was 1.603; (95{\%} Confidence Interval (CI) 1.2–2.143; p-value: 0.01), with the subgroup analysis for miR-21 showing HR for resistance of 2.061; 95{\%} CI 1.195–3.556; p-value: 0.09. Interpretation: Our results highlight multiple miRNAs that have possible associations with modulation of chemotherapy response in pancreatic cancer patients. Further studies are needed to di scover the molecular mechanisms underlying these associations before they can be suggested for use as biomarkers of response to chemotherapeutic interventions in pancreatic cancer.",
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author = "Royam, {Madhav Madurantakam} and Rithika Ramesh and Ritika Shanker and Shanthi Sabarimurugan and Chellan Kumarasamy and Nachimuthu Ramesh and Gothandam, {Kodiveri Muthukalianan} and Siddharta Baxi and Ajay Gupta and Sunil Krishnan and Rama Jayaraj",
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Royam, MM, Ramesh, R, Shanker, R, Sabarimurugan, S, Kumarasamy, C, Ramesh, N, Gothandam, KM, Baxi, S, Gupta, A, Krishnan, S & Jayaraj, R 2019, 'MiRNA predictors of pancreatic cancer chemotherapeutic response: A systematic review and meta-analysis', Cancers, vol. 11, no. 7, 900, pp. 1-25. https://doi.org/10.3390/cancers11070900

MiRNA predictors of pancreatic cancer chemotherapeutic response : A systematic review and meta-analysis. / Royam, Madhav Madurantakam; Ramesh, Rithika; Shanker, Ritika; Sabarimurugan, Shanthi; Kumarasamy, Chellan; Ramesh, Nachimuthu; Gothandam, Kodiveri Muthukalianan; Baxi, Siddharta; Gupta, Ajay; Krishnan, Sunil; Jayaraj, Rama.

In: Cancers, Vol. 11, No. 7, 900, 01.07.2019, p. 1-25.

Research output: Contribution to journalReview articleResearchpeer-review

TY - JOUR

T1 - MiRNA predictors of pancreatic cancer chemotherapeutic response

T2 - A systematic review and meta-analysis

AU - Royam, Madhav Madurantakam

AU - Ramesh, Rithika

AU - Shanker, Ritika

AU - Sabarimurugan, Shanthi

AU - Kumarasamy, Chellan

AU - Ramesh, Nachimuthu

AU - Gothandam, Kodiveri Muthukalianan

AU - Baxi, Siddharta

AU - Gupta, Ajay

AU - Krishnan, Sunil

AU - Jayaraj, Rama

PY - 2019/7/1

Y1 - 2019/7/1

N2 - Background: Pancreatic cancer (PC) has increasing incidence and mortality in developing countries, and drug resistance is a significant hindrance to the efficacy of successful treatment. The objective of this systematic review and meta-analysis was to evaluate the association between miRNAs and response to chemotherapy in pancreatic cancer patients. Methods: The systematic review and meta-analysis was based on articles collected from a thorough search of PubMed and Science Direct databases for publications spanning from January 2008 to December 2018. The articles were screened via a set of inclusion and exclusion criteria based on the preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines. Data was extracted, collated and tabulated in MS Excel for further synthesis. Hazard ratio (HR) was selected as the effect size metric to be pooled across studies for the meta-analysis, with the random effects model being applied. Subgroup analysis was also conducted, and the presence of publication bias in the selected studies was assessed. Publication bias of the included studies was quantified. Findings: Of the 169 articles screened, 43 studies were included in our systematic review and 13 articles were included in the meta-analysis. Gemcitabine was observed to be the principal drug used in a majority of the studies. A total of 48 miRNAs have been studied, and 18 were observed to have possible contributions to chemoresistance, while 15 were observed to have possible contributions to chemosensitivity. 41 drug-related genetic pathways have been identified, through which the highlighted miRNA may be affecting chemosensitivity/resistance. The pooled HR value for overall survival was 1.603; (95% Confidence Interval (CI) 1.2–2.143; p-value: 0.01), with the subgroup analysis for miR-21 showing HR for resistance of 2.061; 95% CI 1.195–3.556; p-value: 0.09. Interpretation: Our results highlight multiple miRNAs that have possible associations with modulation of chemotherapy response in pancreatic cancer patients. Further studies are needed to di scover the molecular mechanisms underlying these associations before they can be suggested for use as biomarkers of response to chemotherapeutic interventions in pancreatic cancer.

AB - Background: Pancreatic cancer (PC) has increasing incidence and mortality in developing countries, and drug resistance is a significant hindrance to the efficacy of successful treatment. The objective of this systematic review and meta-analysis was to evaluate the association between miRNAs and response to chemotherapy in pancreatic cancer patients. Methods: The systematic review and meta-analysis was based on articles collected from a thorough search of PubMed and Science Direct databases for publications spanning from January 2008 to December 2018. The articles were screened via a set of inclusion and exclusion criteria based on the preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines. Data was extracted, collated and tabulated in MS Excel for further synthesis. Hazard ratio (HR) was selected as the effect size metric to be pooled across studies for the meta-analysis, with the random effects model being applied. Subgroup analysis was also conducted, and the presence of publication bias in the selected studies was assessed. Publication bias of the included studies was quantified. Findings: Of the 169 articles screened, 43 studies were included in our systematic review and 13 articles were included in the meta-analysis. Gemcitabine was observed to be the principal drug used in a majority of the studies. A total of 48 miRNAs have been studied, and 18 were observed to have possible contributions to chemoresistance, while 15 were observed to have possible contributions to chemosensitivity. 41 drug-related genetic pathways have been identified, through which the highlighted miRNA may be affecting chemosensitivity/resistance. The pooled HR value for overall survival was 1.603; (95% Confidence Interval (CI) 1.2–2.143; p-value: 0.01), with the subgroup analysis for miR-21 showing HR for resistance of 2.061; 95% CI 1.195–3.556; p-value: 0.09. Interpretation: Our results highlight multiple miRNAs that have possible associations with modulation of chemotherapy response in pancreatic cancer patients. Further studies are needed to di scover the molecular mechanisms underlying these associations before they can be suggested for use as biomarkers of response to chemotherapeutic interventions in pancreatic cancer.

KW - Chemoresistance

KW - Meta-analysis

KW - MiRNAs

KW - Pancreatic cancer

KW - Systematic review

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U2 - 10.3390/cancers11070900

DO - 10.3390/cancers11070900

M3 - Review article

VL - 11

SP - 1

EP - 25

JO - Cancers

JF - Cancers

SN - 2072-6694

IS - 7

M1 - 900

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Royam MM, Ramesh R, Shanker R, Sabarimurugan S, Kumarasamy C, Ramesh N et al. MiRNA predictors of pancreatic cancer chemotherapeutic response: A systematic review and meta-analysis. Cancers. 2019 Jul 1;11(7):1-25. 900. https://doi.org/10.3390/cancers11070900