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      To study the role of pre‐treatment microRNA (micro ribonucleic acid) expression as a predictor of response to chemoradiation in locally advanced carcinoma cervix

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          Abstract

          Background

          Concurrent chemoradiotherapy followed by brachytherapy is the standard of care in locally advanced carcinoma cervix. There is no prognostic factor at present to predict the outcome of disease in locally advanced carcinoma cervix.

          Aim

          Differential expression of microRNAs can be used as biomarkers to predict clinical response in locally advanced carcinoma cervix patients.

          Methods

          Thirty‐two patients of locally advanced carcinoma cervix with International Federation of Gynecology and Obstetrics Stage IB‐IVA were enrolled from 2017 to 2018. Expression of microRNA‐9 5p, ‐31 3p, ‐100 5p, ‐125a 5p, ‐125b‐5p, and –200a 5p in formalin‐fixed paraffin embedded (FFPE) biopsied tissue were analyzed by real time quantitative reverse transcriptase polymerase chain reaction (RT qPCR). Pretreatment evaluation was done with clinical examination and MRI pelvis. All patients received concurrent chemoradiotherapy followed by brachytherapy. Patients were evaluated for the clinical response after 3 months of treatment, with clinical examination and MRI pelvis scan using RECIST 1.1 criteria. Patients with no residual disease were classified as Complete responders (CR) and with residual or progressive disease were classified as Nonresponders (NR). Results were statistically analyzed using Mann Whiney U test to examine significant difference between the expression of microRNA between complete responders (CR) and nonresponders (NR).

          Results

          microRNA‐100 5p was upregulated in complete responders (CR) which showed a trend towards statistical significance ( p value = 0.05).

          Conclusion

          microRNA‐100 5p can serve as a potential molecular biomarker in predicting clinical response to chemoradiation in locally advanced Carcinoma cervix. Its role should be further investigated in a larger study population.

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          Most cited references32

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          Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries

          Ahmedin Jemal, Lindsey A Torre, Rebecca Siegel … (2018)
          This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions. There will be an estimated 18.1 million new cancer cases (17.0 million excluding nonmelanoma skin cancer) and 9.6 million cancer deaths (9.5 million excluding nonmelanoma skin cancer) in 2018. In both sexes combined, lung cancer is the most commonly diagnosed cancer (11.6% of the total cases) and the leading cause of cancer death (18.4% of the total cancer deaths), closely followed by female breast cancer (11.6%), prostate cancer (7.1%), and colorectal cancer (6.1%) for incidence and colorectal cancer (9.2%), stomach cancer (8.2%), and liver cancer (8.2%) for mortality. Lung cancer is the most frequent cancer and the leading cause of cancer death among males, followed by prostate and colorectal cancer (for incidence) and liver and stomach cancer (for mortality). Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death, followed by colorectal and lung cancer (for incidence), and vice versa (for mortality); cervical cancer ranks fourth for both incidence and mortality. The most frequently diagnosed cancer and the leading cause of cancer death, however, substantially vary across countries and within each country depending on the degree of economic development and associated social and life style factors. It is noteworthy that high-quality cancer registry data, the basis for planning and implementing evidence-based cancer control programs, are not available in most low- and middle-income countries. The Global Initiative for Cancer Registry Development is an international partnership that supports better estimation, as well as the collection and use of local data, to prioritize and evaluate national cancer control efforts. CA: A Cancer Journal for Clinicians 2018;0:1-31. © 2018 American Cancer Society.
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            Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.

            Kenneth Livak, Thomas D. Schmittgen (2001)
            The two most commonly used methods to analyze data from real-time, quantitative PCR experiments are absolute quantification and relative quantification. Absolute quantification determines the input copy number, usually by relating the PCR signal to a standard curve. Relative quantification relates the PCR signal of the target transcript in a treatment group to that of another sample such as an untreated control. The 2(-Delta Delta C(T)) method is a convenient way to analyze the relative changes in gene expression from real-time quantitative PCR experiments. The purpose of this report is to present the derivation, assumptions, and applications of the 2(-Delta Delta C(T)) method. In addition, we present the derivation and applications of two variations of the 2(-Delta Delta C(T)) method that may be useful in the analysis of real-time, quantitative PCR data. Copyright 2001 Elsevier Science (USA).
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              New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1).

              E A Eisenhauer, P Therasse, J. Bogaerts … (2009)
              Assessment of the change in tumour burden is an important feature of the clinical evaluation of cancer therapeutics: both tumour shrinkage (objective response) and disease progression are useful endpoints in clinical trials. Since RECIST was published in 2000, many investigators, cooperative groups, industry and government authorities have adopted these criteria in the assessment of treatment outcomes. However, a number of questions and issues have arisen which have led to the development of a revised RECIST guideline (version 1.1). Evidence for changes, summarised in separate papers in this special issue, has come from assessment of a large data warehouse (>6500 patients), simulation studies and literature reviews. HIGHLIGHTS OF REVISED RECIST 1.1: Major changes include: Number of lesions to be assessed: based on evidence from numerous trial databases merged into a data warehouse for analysis purposes, the number of lesions required to assess tumour burden for response determination has been reduced from a maximum of 10 to a maximum of five total (and from five to two per organ, maximum). Assessment of pathological lymph nodes is now incorporated: nodes with a short axis of 15 mm are considered measurable and assessable as target lesions. The short axis measurement should be included in the sum of lesions in calculation of tumour response. Nodes that shrink to <10mm short axis are considered normal. Confirmation of response is required for trials with response primary endpoint but is no longer required in randomised studies since the control arm serves as appropriate means of interpretation of data. Disease progression is clarified in several aspects: in addition to the previous definition of progression in target disease of 20% increase in sum, a 5mm absolute increase is now required as well to guard against over calling PD when the total sum is very small. Furthermore, there is guidance offered on what constitutes 'unequivocal progression' of non-measurable/non-target disease, a source of confusion in the original RECIST guideline. Finally, a section on detection of new lesions, including the interpretation of FDG-PET scan assessment is included. Imaging guidance: the revised RECIST includes a new imaging appendix with updated recommendations on the optimal anatomical assessment of lesions. A key question considered by the RECIST Working Group in developing RECIST 1.1 was whether it was appropriate to move from anatomic unidimensional assessment of tumour burden to either volumetric anatomical assessment or to functional assessment with PET or MRI. It was concluded that, at present, there is not sufficient standardisation or evidence to abandon anatomical assessment of tumour burden. The only exception to this is in the use of FDG-PET imaging as an adjunct to determination of progression. As is detailed in the final paper in this special issue, the use of these promising newer approaches requires appropriate clinical validation studies.
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                Author and article information

                Contributors
                Soumitra Barik:
                ORCID: https://orcid.org/0000-0002-8777-7167
                soumitra.barik@gmail.com
                Journal
                Journal ID (nlm-ta): Cancer Rep (Hoboken)
                Journal ID (iso-abbrev): Cancer Rep (Hoboken)
                Journal ID (doi): 10.1002/(ISSN)2573-8348
                Journal ID (publisher-id): CNR2
                Title: Cancer Reports
                Publisher: John Wiley and Sons Inc. (Hoboken )
                ISSN (Electronic): 2573-8348
                Publication date (Electronic): 03 March 2021
                Publication date Collection: August 2021
                Volume: 4
                Issue: 4 ( doiID: 10.1002/cnr2.v4.4 )
                Electronic Location Identifier: e1348
                Affiliations
                [ 1 ] Department of Radiation Oncology Rajiv Gandhi Cancer Institute and Research Centre New Delhi India
                [ 2 ] Department of Molecular Biology Rajiv Gandhi Cancer Institute and Research Centre New Delhi India
                [ 3 ] Department of Biostatistics Rajiv Gandhi Cancer Institute and Research Centre New Delhi India
                Author notes
                [*] [* ] Correspondence

                Soumitra Barik, Department of Radiation Oncology, Rajiv Gandhi Cancer Institute and Research Centre, Sector‐5, Rohini, New Delhi 110085, India.

                Email: soumitra.barik@ 123456gmail.com

                Author information
                https://orcid.org/0000-0002-8777-7167
                https://orcid.org/0000-0002-2670-2559
                Article
                Publisher ID: CNR21348
                DOI: 10.1002/cnr2.1348
                PMC ID: 8388174
                PubMed ID: 33660436
                SO-VID: 4fe4571f-6e0a-4eee-aa2b-e9b8010f723a
                Copyright © © 2021 The Authors. Cancer Reports published by Wiley Periodicals LLC.
                License:

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                Date revision received : 14 December 2020
                Date received : 12 August 2020
                Date accepted : 19 January 2021
                Page count
                Figures: 1, Tables: 2, Pages: 6, Words: 4206
                Categories
                Subject: Original Article
                Subject: Original Articles
                Custom metadata
                source-schema-version-number 2.0
                cover-date August 2021
                details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_JATSPMC version:6.0.6 mode:remove_FC converted:26.08.2021

                Keywords: biological markers,carcinoma cervix,concurrent chemoradiotherapy,micrornas,prognosis
                Data availability:
                Keywords: biological markers, carcinoma cervix, concurrent chemoradiotherapy, micrornas, prognosis

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