Latest technique Published on 14 Mar, 2024

A Novel Approach in Elucidating the Interaction of Ecology, Biology and Social (Eco-bio-social) Factors with Serum Metabolites and Its Pathway among Polyps and Colorectal Cancer: A Study Protocol

EBS Factors with CRC and Polyps
Vol. 19 No. 1 : 2024 (336-347)

Abu Bakar MF Abu Bakar MF
Mohammed Nawi A Mohammed Nawi A
chin sf chin sf
Makpol S Makpol S

Abstract
The increasing number of colorectal cancer (CRC) incidences and mortality rates have caused an increasing burden on the healthcare system of the involved countries. This will impact the important economic components as a burden including direct medical care and non-medical costs and have caused productivity losses among patients and caregivers. Early diagnosis is important to help in reducing mortality rates of CRC and enhancing disease treatments. Besides genetic pathways, lifestyle imbalance and environmental factors also are reported as the main causes of CRC. However, most of the previous studies only focused on one factor at a time which limit the understanding of how these factors could be manipulated in the disease biomarkers finding. Hence, this study helps to build a novel protocol to provide a better insight into the effects of the ecology, biology, and social factors on the differential level of a polyp and CRC serum metabolites that could potentially be used to distinguish patients with polyp or CRC. The finding of the study could serve as a potential biomarker that could be used in the development of new screening tools to enhance early screening of polyps and CRC.
Keywords : Serum biomarker, Colorectal cancer, Polyps, Eco-bio-social factors, screening tool,
Abstrak
Peningkatan jumlah insiden dan kadar kematian disebabkan oleh kanser kolorektal (KKR) telah menyebabkan peningkatan beban kepada sistem penjagaan kesihatan negara-negara yang terlibat. Ini telah memberi kesan kepada komponen ekonomi yang penting sebagai satu beban yang ditanggung oleh sesebuah negara termasuklah penjagaan perubatan dan kos bukan perubatan yang telah menyebabkan kerugian produktiviti di kalangan pesakit dan penjaga. Diagnosis awal adalah penting untuk membantu dalam mengurangkan kadar kematian disebabkan oleh KKR dan meningkatkan keberkesanan rawatan penyakit. Selain faktor genetik, ketidakseimbangan gaya hidup dan faktor persekitaran juga dilaporkan sebagai punca utama KKR. Walau bagaimanapun, kebanyakan kajian terdahulu hanya memberi tumpuan kepada satu faktor pada satu masa di  mana ia telah menghadkan pemahaman tentang bagaimana faktor-faktor ini boleh dimanipulasi untuk mengkaji penanda-bio penyakit. Oleh itu, kajian ini membantu dalam membina protokol baru untuk memberikan gambaran yang lebih baik mengenai kesan ekologi, biologi, dan faktor sosial yang mungkin mempengaruhi tahap pembezaan serum metabolit bagi polip dan KKR yang berpotensi digunakan untuk membezakan pesakit dengan polip atau KKR. Penemuan kajian ini berpotensi untuk mengenalpasti penanda-bio dari serum yang boleh digunakan dalam pembangunan alat saringan baru untuk meningkatkan kadar saringan awal polip dan KKR.
Kata Kunci : Alat saringan, ekobiososial faktor, kanser kolorektal, penanda-bio serum, polip,

Correspondance Address
Assoc. Prof. Dr Azmawati Mohammed Nawi. Department of Public Health Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latiff, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia. Tel: +6019-3131340 Email: azmawati@ppukm.ukm.edu.my

References
Alqahtani, M.Z., Mohammed, A.G., Alsamghan, A.S., Bharti, R.K., Alsharm, A.A., Alshahrani, M.T., Alzahrani, M.A., Ayed, A.A.N., Alsaleem, M.A., Ghazwani, E.Y. (2020). Risk factors of colorectal cancer among Saudi Population: Case-control study. J Family Med Prim Care 9(9): 5035-40.

Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R.L., Torre, L.A., Jemal, A. 2018. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68(6): 394-424.

Chang, V.C., Cotterchio, M., De, P., Tinmouth, J. 2021. Risk factors for early-onset colorectal cancer: a population-based case–control study in Ontario, Canada. Cancer Causes Control 32(10): 1063-83.

Cho, Y.A., Lee, J., Oh, J.H., Chang, H.J., Sohn, D.K., Shin, A., Kim, J. 2019. Genetic risk score, combined lifestyle factors and risk of colorectal cancer. Cancer Res Treat 51(3): 1033-40.

Dupont, W.D., Plummer Jr, W.D. 1998. Power and sample size calculations for studies involving linear regression. Control Clin Trials 19(6): 589-601.

Fan, S., Shahid, M., Jin, P., Asher, A., Kim, J. 2020. Identification of metabolic alterations in breast cancer using mass spectrometry-based metabolomic analysis. Metabolites 10(4): 170.

Gonzalez-Pons, M., Cruz-Correa, M. 2015. Colorectal cancer biomarkers: Where are we now?. BioMed Res Int 2015: 149014.

Hashim, N.A.A., Ab-Rahim, S., Ngah, W.Z.W., Nathan, S., Ab Mutalib, N.S., Sagap, I., Jamal, A.R.A., Mazlan, M. 2021. Global metabolomics profiling of colorectal cancer in Malaysian patients. BioImpacts 11(1): 33.

IBM Corp. Released 2021. IBM SPSS Statistics for Windows, Version 28.0. Armonk, NY: IBM Corp.

Kessels, K., Eisinger, J.D., Letteboer, T.G., Offerhaus, G.J.A., Siersema, P.D., Moons, L.M. 2017. Sending family history questionnaires to patients before a colonoscopy improves genetic counseling for hereditary colorectal cancer. J Dig Dis 18(6): 343-8.

Long, Y., Sanchez-Espiridion, B., Lin, M., White, L., Mishra, L., Raju, G.S., Kopetz, S., Eng, C., Hildebrandt, M.A., Chang, D.W., Ye, Y. 2017. Global and targeted serum metabolic profiling of colorectal cancer progression. Cancer 123(20): 4066-74.

Montenegro-Burke, J.R., Guijas, C., Siuzdak, G. 2020. METLIN: A tandem mass spectral library of standards. Methods Mol Biol 2104: 149-63.

Nawi, A.M., Chin, S.F., Mazlan, L., Jamal, R. 2020. Delineating colorectal cancer distribution, interaction, and risk prediction by environmental risk factors and serum trace elements. Sci Rep 10(1): 18670.

Nishiumi, S., Kobayashi, T., Ikeda, A., Yoshie, T., Kibi, M., Izumi, Y., Okuno, T., Hayashi, N., Kawano, S., Takenawa, T., Azuma, T. 2012. A novel serum metabolomics-based diagnostic approach for colorectal cancer. PloS ONE 7(7): e40459.

Norsa’adah, B., Aminu, A.R., Zaidi, Z. 2020. Validity and reliability of questionnaire on knowledge, attitude and dietary practices related to colorectal cancer. Malays J Med Sci 27(1): 115-23.

Pang, Z., Chong, J., Zhou, G., de Lima Morais, D.A., Chang, L., Barrette, M., Gauthier, C., Jacques, P.É., Li, S., Xia, J. 2021. MetaboAnalyst 5.0: Narrowing the gap between raw spectra and functional insights. Nucleic Acids Res 49(W1): W388-W396.

Rawla, P., Sunkara, T., Barsouk, A. 2019. Epidemiology of colorectal cancer: Incidence, mortality, survival, and risk factors. Prz Gastroenterol 14(2): 89-103.

Sawicki, T., Ruszkowska, M., Danielewicz, A., Niedźwiedzka, E., Arłukowicz, T., Przybyłowicz, K.E. 2021. A review of colorectal cancer in terms of epidemiology, risk factors, development, symptoms and diagnosis. Cancers 13(9): 2025.

Siegel, R.L., Miller, K.D., Goding Sauer, A., Fedewa, S.A., Butterly, L.F., Anderson, J.C., Cercek, A., Smith, R.A., Jemal, A. 2020. Colorectal cancer statistics, 2020. CA Cancer J Clin 70(3): 145-64.

Soffian, S.S.S., Nawi, A.M., Hod, R., Chan, H.K., Hassan, M.R.A. 2021. Area-level determinants in colorectal cancer spatial clustering studies: a systematic review. Int J Environ Res Public Health 18(19): 10486.

StataCorp. 2021. Stata Statistical Software: Release 17. College Station, TX: StataCorp LLC.

Su, T.T., Goh, J.Y., Tan, J., Muhaimah, A.R., Pigeneswaren, Y., Khairun, N.S., Normazidah, A.W., Tharisini, D.K., Majid, H.A., 2013. Level of colorectal cancer awareness: A cross sectional exploratory study among multi-ethnic rural population in Malaysia. BMC Cancer 13(1): 1-8.

Takahashi, N., Nakao, M. 2021. Social-life factors associated with participation in screening and further assessment of colorectal cancer: A nationwide ecological study in Japanese municipalities. SSM Popul Health 15: 100839.

Tan, B., Qiu, Y., Zou, X., Chen, T., Xie, G., Cheng, Y., Dong, T., Zhao, L., Feng, B., Hu, X., Xu, L.X., Zhao, A., Zhang, M., Cai, G., Cai, S., Zhou, Z., Zheng, M., Zhang, Y., Jia, W. 2013. Metabonomics identifies serum metabolite markers of colorectal cancer. J Proteome Res 12(6): 3000-9.

Tepus, M., Yau, T.O. 2020. Non-invasive colorectal cancer screening: An overview. Gastrointest Tumors 7(3): 62-73.

Ulaganathan, V., Kandiah, M., Shariff, Z.M. 2018. A case–control study on the association of abdominal obesity and hypercholesterolemia with the risk of colorectal cancer. J Carcinog 17: 4.

Vega, P., Valentin, F., Cubiella, J. 2015. Colorectal cancer diagnosis: Pitfalls and opportunities. World J Gastrointest Oncol 7(12): 422.

World Health Organization (WHO). Cancer Country Profile Report 2020. International Agency for Research on Cancer (IARC). Available at https://gco.iarc.fr/ [Accessed 27 May 2022]

World Medical Association. WMA Declaration of Helsinki: ethical principles for medical research involving human subjects, 2018. Available: https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects/ [Accessed 6 February 2023].

Zhou, X., Xu, X., Wang, J., Lin, J., Chen, W. 2015. Identifying miRNA/mRNA negative regulation pairs in colorectal cancer. Sci Rep 5(1): 12995.
Correspondance Address

Alqahtani, M.Z., Mohammed, A.G., Alsamghan, A.S., Bharti, R.K., Alsharm, A.A., Alshahrani, M.T., Alzahrani, M.A., Ayed, A.A.N., Alsaleem, M.A., Ghazwani, E.Y. (2020). Risk factors of colorectal cancer among Saudi Population: Case-control study. J Family Med Prim Care 9(9): 5035-40.

Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R.L., Torre, L.A., Jemal, A. 2018. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68(6): 394-424.

Chang, V.C., Cotterchio, M., De, P., Tinmouth, J. 2021. Risk factors for early-onset colorectal cancer: a population-based case–control study in Ontario, Canada. Cancer Causes Control 32(10): 1063-83.

Cho, Y.A., Lee, J., Oh, J.H., Chang, H.J., Sohn, D.K., Shin, A., Kim, J. 2019. Genetic risk score, combined lifestyle factors and risk of colorectal cancer. Cancer Res Treat 51(3): 1033-40.

Dupont, W.D., Plummer Jr, W.D. 1998. Power and sample size calculations for studies involving linear regression. Control Clin Trials 19(6): 589-601.

Fan, S., Shahid, M., Jin, P., Asher, A., Kim, J. 2020. Identification of metabolic alterations in breast cancer using mass spectrometry-based metabolomic analysis. Metabolites 10(4): 170.

Gonzalez-Pons, M., Cruz-Correa, M. 2015. Colorectal cancer biomarkers: Where are we now?. BioMed Res Int 2015: 149014.

Hashim, N.A.A., Ab-Rahim, S., Ngah, W.Z.W., Nathan, S., Ab Mutalib, N.S., Sagap, I., Jamal, A.R.A., Mazlan, M. 2021. Global metabolomics profiling of colorectal cancer in Malaysian patients. BioImpacts 11(1): 33.

IBM Corp. Released 2021. IBM SPSS Statistics for Windows, Version 28.0. Armonk, NY: IBM Corp.

Kessels, K., Eisinger, J.D., Letteboer, T.G., Offerhaus, G.J.A., Siersema, P.D., Moons, L.M. 2017. Sending family history questionnaires to patients before a colonoscopy improves genetic counseling for hereditary colorectal cancer. J Dig Dis 18(6): 343-8.

Long, Y., Sanchez-Espiridion, B., Lin, M., White, L., Mishra, L., Raju, G.S., Kopetz, S., Eng, C., Hildebrandt, M.A., Chang, D.W., Ye, Y. 2017. Global and targeted serum metabolic profiling of colorectal cancer progression. Cancer 123(20): 4066-74.

Montenegro-Burke, J.R., Guijas, C., Siuzdak, G. 2020. METLIN: A tandem mass spectral library of standards. Methods Mol Biol 2104: 149-63.

Nawi, A.M., Chin, S.F., Mazlan, L., Jamal, R. 2020. Delineating colorectal cancer distribution, interaction, and risk prediction by environmental risk factors and serum trace elements. Sci Rep 10(1): 18670.

Nishiumi, S., Kobayashi, T., Ikeda, A., Yoshie, T., Kibi, M., Izumi, Y., Okuno, T., Hayashi, N., Kawano, S., Takenawa, T., Azuma, T. 2012. A novel serum metabolomics-based diagnostic approach for colorectal cancer. PloS ONE 7(7): e40459.

Norsa’adah, B., Aminu, A.R., Zaidi, Z. 2020. Validity and reliability of questionnaire on knowledge, attitude and dietary practices related to colorectal cancer. Malays J Med Sci 27(1): 115-23.

Pang, Z., Chong, J., Zhou, G., de Lima Morais, D.A., Chang, L., Barrette, M., Gauthier, C., Jacques, P.É., Li, S., Xia, J. 2021. MetaboAnalyst 5.0: Narrowing the gap between raw spectra and functional insights. Nucleic Acids Res 49(W1): W388-W396.

Rawla, P., Sunkara, T., Barsouk, A. 2019. Epidemiology of colorectal cancer: Incidence, mortality, survival, and risk factors. Prz Gastroenterol 14(2): 89-103.

Sawicki, T., Ruszkowska, M., Danielewicz, A., Niedźwiedzka, E., Arłukowicz, T., Przybyłowicz, K.E. 2021. A review of colorectal cancer in terms of epidemiology, risk factors, development, symptoms and diagnosis. Cancers 13(9): 2025.

Siegel, R.L., Miller, K.D., Goding Sauer, A., Fedewa, S.A., Butterly, L.F., Anderson, J.C., Cercek, A., Smith, R.A., Jemal, A. 2020. Colorectal cancer statistics, 2020. CA Cancer J Clin 70(3): 145-64.

Soffian, S.S.S., Nawi, A.M., Hod, R., Chan, H.K., Hassan, M.R.A. 2021. Area-level determinants in colorectal cancer spatial clustering studies: a systematic review. Int J Environ Res Public Health 18(19): 10486.

StataCorp. 2021. Stata Statistical Software: Release 17. College Station, TX: StataCorp LLC.

Su, T.T., Goh, J.Y., Tan, J., Muhaimah, A.R., Pigeneswaren, Y., Khairun, N.S., Normazidah, A.W., Tharisini, D.K., Majid, H.A., 2013. Level of colorectal cancer awareness: A cross sectional exploratory study among multi-ethnic rural population in Malaysia. BMC Cancer 13(1): 1-8.

Takahashi, N., Nakao, M. 2021. Social-life factors associated with participation in screening and further assessment of colorectal cancer: A nationwide ecological study in Japanese municipalities. SSM Popul Health 15: 100839.

Tan, B., Qiu, Y., Zou, X., Chen, T., Xie, G., Cheng, Y., Dong, T., Zhao, L., Feng, B., Hu, X., Xu, L.X., Zhao, A., Zhang, M., Cai, G., Cai, S., Zhou, Z., Zheng, M., Zhang, Y., Jia, W. 2013. Metabonomics identifies serum metabolite markers of colorectal cancer. J Proteome Res 12(6): 3000-9.

Tepus, M., Yau, T.O. 2020. Non-invasive colorectal cancer screening: An overview. Gastrointest Tumors 7(3): 62-73.

Ulaganathan, V., Kandiah, M., Shariff, Z.M. 2018. A case–control study on the association of abdominal obesity and hypercholesterolemia with the risk of colorectal cancer. J Carcinog 17: 4.

Vega, P., Valentin, F., Cubiella, J. 2015. Colorectal cancer diagnosis: Pitfalls and opportunities. World J Gastrointest Oncol 7(12): 422.

World Health Organization (WHO). Cancer Country Profile Report 2020. International Agency for Research on Cancer (IARC). Available at https://gco.iarc.fr/ [Accessed 27 May 2022]

World Medical Association. WMA Declaration of Helsinki: ethical principles for medical research involving human subjects, 2018. Available: https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-p… [Accessed 6 February 2023].

Zhou, X., Xu, X., Wang, J., Lin, J., Chen, W. 2015. Identifying miRNA/mRNA negative regulation pairs in colorectal cancer. Sci Rep 5(1): 12995.



Alqahtani, M.Z., Mohammed, A.G., Alsamghan, A.S., Bharti, R.K., Alsharm, A.A., Alshahrani, M.T., Alzahrani, M.A., Ayed, A.A.N., Alsaleem, M.A., Ghazwani, E.Y. (2020). Risk factors of colorectal cancer among Saudi Population: Case-control study. J Family Med Prim Care 9(9): 5035-40.

Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R.L., Torre, L.A., Jemal, A. 2018. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68(6): 394-424.

Chang, V.C., Cotterchio, M., De, P., Tinmouth, J. 2021. Risk factors for early-onset colorectal cancer: a population-based case–control study in Ontario, Canada. Cancer Causes Control 32(10): 1063-83.

Cho, Y.A., Lee, J., Oh, J.H., Chang, H.J., Sohn, D.K., Shin, A., Kim, J. 2019. Genetic risk score, combined lifestyle factors and risk of colorectal cancer. Cancer Res Treat 51(3): 1033-40.

Dupont, W.D., Plummer Jr, W.D. 1998. Power and sample size calculations for studies involving linear regression. Control Clin Trials 19(6): 589-601.

Fan, S., Shahid, M., Jin, P., Asher, A., Kim, J. 2020. Identification of metabolic alterations in breast cancer using mass spectrometry-based metabolomic analysis. Metabolites 10(4): 170.

Gonzalez-Pons, M., Cruz-Correa, M. 2015. Colorectal cancer biomarkers: Where are we now?. BioMed Res Int 2015: 149014.

Hashim, N.A.A., Ab-Rahim, S., Ngah, W.Z.W., Nathan, S., Ab Mutalib, N.S., Sagap, I., Jamal, A.R.A., Mazlan, M. 2021. Global metabolomics profiling of colorectal cancer in Malaysian patients. BioImpacts 11(1): 33.

IBM Corp. Released 2021. IBM SPSS Statistics for Windows, Version 28.0. Armonk, NY: IBM Corp.

Kessels, K., Eisinger, J.D., Letteboer, T.G., Offerhaus, G.J.A., Siersema, P.D., Moons, L.M. 2017. Sending family history questionnaires to patients before a colonoscopy improves genetic counseling for hereditary colorectal cancer. J Dig Dis 18(6): 343-8.

Long, Y., Sanchez-Espiridion, B., Lin, M., White, L., Mishra, L., Raju, G.S., Kopetz, S., Eng, C., Hildebrandt, M.A., Chang, D.W., Ye, Y. 2017. Global and targeted serum metabolic profiling of colorectal cancer progression. Cancer 123(20): 4066-74.

Montenegro-Burke, J.R., Guijas, C., Siuzdak, G. 2020. METLIN: A tandem mass spectral library of standards. Methods Mol Biol 2104: 149-63.

Nawi, A.M., Chin, S.F., Mazlan, L., Jamal, R. 2020. Delineating colorectal cancer distribution, interaction, and risk prediction by environmental risk factors and serum trace elements. Sci Rep 10(1): 18670.

Nishiumi, S., Kobayashi, T., Ikeda, A., Yoshie, T., Kibi, M., Izumi, Y., Okuno, T., Hayashi, N., Kawano, S., Takenawa, T., Azuma, T. 2012. A novel serum metabolomics-based diagnostic approach for colorectal cancer. PloS ONE 7(7): e40459.

Norsa’adah, B., Aminu, A.R., Zaidi, Z. 2020. Validity and reliability of questionnaire on knowledge, attitude and dietary practices related to colorectal cancer. Malays J Med Sci 27(1): 115-23.

Pang, Z., Chong, J., Zhou, G., de Lima Morais, D.A., Chang, L., Barrette, M., Gauthier, C., Jacques, P.É., Li, S., Xia, J. 2021. MetaboAnalyst 5.0: Narrowing the gap between raw spectra and functional insights. Nucleic Acids Res 49(W1): W388-W396.

Rawla, P., Sunkara, T., Barsouk, A. 2019. Epidemiology of colorectal cancer: Incidence, mortality, survival, and risk factors. Prz Gastroenterol 14(2): 89-103.

Sawicki, T., Ruszkowska, M., Danielewicz, A., Niedźwiedzka, E., Arłukowicz, T., Przybyłowicz, K.E. 2021. A review of colorectal cancer in terms of epidemiology, risk factors, development, symptoms and diagnosis. Cancers 13(9): 2025.

Siegel, R.L., Miller, K.D., Goding Sauer, A., Fedewa, S.A., Butterly, L.F., Anderson, J.C., Cercek, A., Smith, R.A., Jemal, A. 2020. Colorectal cancer statistics, 2020. CA Cancer J Clin 70(3): 145-64.

Soffian, S.S.S., Nawi, A.M., Hod, R., Chan, H.K., Hassan, M.R.A. 2021. Area-level determinants in colorectal cancer spatial clustering studies: a systematic review. Int J Environ Res Public Health 18(19): 10486.

StataCorp. 2021. Stata Statistical Software: Release 17. College Station, TX: StataCorp LLC.

Su, T.T., Goh, J.Y., Tan, J., Muhaimah, A.R., Pigeneswaren, Y., Khairun, N.S., Normazidah, A.W., Tharisini, D.K., Majid, H.A., 2013. Level of colorectal cancer awareness: A cross sectional exploratory study among multi-ethnic rural population in Malaysia. BMC Cancer 13(1): 1-8.

Takahashi, N., Nakao, M. 2021. Social-life factors associated with participation in screening and further assessment of colorectal cancer: A nationwide ecological study in Japanese municipalities. SSM Popul Health 15: 100839.

Tan, B., Qiu, Y., Zou, X., Chen, T., Xie, G., Cheng, Y., Dong, T., Zhao, L., Feng, B., Hu, X., Xu, L.X., Zhao, A., Zhang, M., Cai, G., Cai, S., Zhou, Z., Zheng, M., Zhang, Y., Jia, W. 2013. Metabonomics identifies serum metabolite markers of colorectal cancer. J Proteome Res 12(6): 3000-9.

Tepus, M., Yau, T.O. 2020. Non-invasive colorectal cancer screening: An overview. Gastrointest Tumors 7(3): 62-73.

Ulaganathan, V., Kandiah, M., Shariff, Z.M. 2018. A case–control study on the association of abdominal obesity and hypercholesterolemia with the risk of colorectal cancer. J Carcinog 17: 4.

Vega, P., Valentin, F., Cubiella, J. 2015. Colorectal cancer diagnosis: Pitfalls and opportunities. World J Gastrointest Oncol 7(12): 422.

World Health Organization (WHO). Cancer Country Profile Report 2020. International Agency for Research on Cancer (IARC). Available at https://gco.iarc.fr/ [Accessed 27 May 2022]

World Medical Association. WMA Declaration of Helsinki: ethical principles for medical research involving human subjects, 2018. Available: https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-p… [Accessed 6 February 2023].

Zhou, X., Xu, X., Wang, J., Lin, J., Chen, W. 2015. Identifying miRNA/mRNA negative regulation pairs in colorectal cancer. Sci Rep 5(1): 12995.