Signal Transduction Pathway Mutations in Gastrointestinal (GI) Cancers: a Systematic Review and Meta-analysis

Overview

Journal Sci Rep

Specialty Science

Date 2020 Oct 31

PMID 33127962

Citations 10

Authors

Alireza Tabibzadeh

Fahimeh Safarnezhad Tameshkel

Yousef Moradi

Saber Soltani

Maziar Moradi-Lakeh

G Hossein Ashrafi

Nima Motamed

Farhad Zamani

Seyed Abbas Motevalian

Mahshid Panahi

Maryam Esghaei

Hossein Ajdarkosh

Alireza Mousavi-Jarrahi

Mohammad Hadi Karbalaie Niya

Affiliations

Soon will be listed here.

Abstract

The present study was conducted to evaluate the prevalence of the signaling pathways mutation rate in the Gastrointestinal (GI) tract cancers in a systematic review and meta-analysis study. The study was performed based on the PRISMA criteria. Random models by confidence interval (CI: 95%) were used to calculate the pooled estimate of prevalence via Metaprop command. The pooled prevalence indices of signal transduction pathway mutations in gastric cancer, liver cancer, colorectal cancer, and pancreatic cancer were 5% (95% CI: 3-8%), 12% (95% CI: 8-18%), 17% (95% CI: 14-20%), and 20% (95% CI: 5-41%), respectively. Also, the mutation rates for Wnt pathway and MAPK pathway were calculated to be 23% (95% CI, 14-33%) and 20% (95% CI, 17-24%), respectively. Moreover, the most popular genes were APC (in Wnt pathway), KRAS (in MAPK pathway) and PIK3CA (in PI3K pathway) in the colorectal cancer, pancreatic cancer, and gastric cancer while they were beta-catenin and CTNNB1 in liver cancer. The most altered pathway was Wnt pathway followed by the MAPK pathway. In addition, pancreatic cancer was found to be higher under the pressure of mutation compared with others based on pooled prevalence analysis. Finally, APC mutations in colorectal cancer, KRAS in gastric cancer, and pancreatic cancer were mostly associated gene alterations.

Citing Articles

Comprehensive analysis of inhibin-β A as a potential biomarker for gastrointestinal tract cancers through bioinformatics approaches.

Verma R, Srivastava P, Singh A Sci Rep. 2025; 15(1):1090.

PMID: 39774945 PMC: 11707248. DOI: 10.1038/s41598-024-72679-3.

Progress on angiogenic and antiangiogenic agents in the tumor microenvironment.

Xu J, Tang Z Front Oncol. 2024; 14:1491099.

PMID: 39629004 PMC: 11611712. DOI: 10.3389/fonc.2024.1491099.

Interaction of the AKT and β-catenin signalling pathways and the influence of photobiomodulation on cellular signalling proteins in diabetic wound healing.

Jere S, Abrahamse H, Houreld N J Biomed Sci. 2023; 30(1):81.

PMID: 37735655 PMC: 10515080. DOI: 10.1186/s12929-023-00974-8.

Nuclear Expression of β-Catenin Is Associated with Improved Outcomes in Endometrial Cancer.

Masciullo V, Susini T, Corrado G, Stepanova M, Baroni A, Renda I Diagnostics (Basel). 2022; 12(10).

PMID: 36292090 PMC: 9600744. DOI: 10.3390/diagnostics12102401.

Regulatory effect of traditional Chinese medicines on signaling pathways of process from chronic atrophic gastritis to gastric cancer.

Liu X, Wang S, Li J, Zhang J, Liu D Chin Herb Med. 2022; 14(1):5-19.

PMID: 36120132 PMC: 9476726. DOI: 10.1016/j.chmed.2021.10.008.

References

Tai C, Chang C, Jiang M, Yeh C, Su T, Wu P . Clinical-pathological correlation of K-Ras mutation and ERK phosphorylation in colorectal cancer. Pol J Pathol. 2012; 63(2):93-100. View

Catenacci D, Cervantes G, Yala S, Nelson E, El-Hashani E, Kanteti R . RON (MST1R) is a novel prognostic marker and therapeutic target for gastroesophageal adenocarcinoma. Cancer Biol Ther. 2011; 12(1):9-46. PMC: 3149873. DOI: 10.4161/cbt.12.1.15747. View

Sameer A, Shah Z, Abdullah S, Chowdri N, Siddiqi M . Analysis of molecular aberrations of Wnt pathway gladiators in colorectal cancer in the Kashmiri population. Hum Genomics. 2011; 5(5):441-52. PMC: 3525962. DOI: 10.1186/1479-7364-5-5-441. View

Sameer A, Chowdri N, Syeed N, Banday M, Shah Z, Siddiqi M . SMAD4--molecular gladiator of the TGF-beta signaling is trampled upon by mutational insufficiency in colorectal carcinoma of Kashmiri population: an analysis with relation to KRAS proto-oncogene. BMC Cancer. 2010; 10:300. PMC: 2927996. DOI: 10.1186/1471-2407-10-300. View

Sukawa Y, Yamamoto H, Nosho K, Kunimoto H, Suzuki H, Adachi Y . Alterations in the human epidermal growth factor receptor 2-phosphatidylinositol 3-kinase-v-Akt pathway in gastric cancer. World J Gastroenterol. 2012; 18(45):6577-86. PMC: 3516204. DOI: 10.3748/wjg.v18.i45.6577. View

Xie H, Bae H, Noh J, Eun J, Kim J, Jung K . Mutational analysis of JAK1 gene in human hepatocellular carcinoma. Neoplasma. 2009; 56(2):136-40. DOI: 10.4149/neo_2009_02_136. View

Kondo Y, Kanai Y, Sakamoto M, Genda T, Mizokami M, Ueda R . Beta-catenin accumulation and mutation of exon 3 of the beta-catenin gene in hepatocellular carcinoma. Jpn J Cancer Res. 2000; 90(12):1301-9. PMC: 5926034. DOI: 10.1111/j.1349-7006.1999.tb00712.x. View

Hidaka Y, Mitomi H, Saito T, Takahashi M, Lee S, Matsumoto K . Alteration in the Wnt/β-catenin signaling pathway in gastric neoplasias of fundic gland (chief cell predominant) type. Hum Pathol. 2013; 44(11):2438-48. DOI: 10.1016/j.humpath.2013.06.002. View

Wang X, Inzunza H, Chang H, Qi Z, Hu B, Malone D . Mutations in the hedgehog pathway genes SMO and PTCH1 in human gastric tumors. PLoS One. 2013; 8(1):e54415. PMC: 3548780. DOI: 10.1371/journal.pone.0054415. View

10.

Lee S, Haq F, Kim D, Jun C, Jo H, Ahn S . Comparative genomic analysis of primary and synchronous metastatic colorectal cancers. PLoS One. 2014; 9(3):e90459. PMC: 3944022. DOI: 10.1371/journal.pone.0090459. View

11.

Stegh A . Targeting the p53 signaling pathway in cancer therapy - the promises, challenges and perils. Expert Opin Ther Targets. 2012; 16(1):67-83. PMC: 3291789. DOI: 10.1517/14728222.2011.643299. View

12.

Irahara N, Baba Y, Nosho K, Shima K, Yan L, Dias-Santagata D . NRAS mutations are rare in colorectal cancer. Diagn Mol Pathol. 2010; 19(3):157-63. PMC: 2929976. DOI: 10.1097/PDM.0b013e3181c93fd1. View

13.

Liang P, Chen T, Giovannucci E . Cigarette smoking and colorectal cancer incidence and mortality: systematic review and meta-analysis. Int J Cancer. 2009; 124(10):2406-15. DOI: 10.1002/ijc.24191. View

14.

Samara M, Kapatou K, Ioannou M, Kostopoulou E, Papamichali R, Papandreou C . Mutation profile of KRAS and BRAF genes in patients with colorectal cancer: association with morphological and prognostic criteria. Genet Mol Res. 2015; 14(4):16793-802. DOI: 10.4238/2015.December.14.6. View

15.

Seth R, Crook S, Ibrahem S, Fadhil W, Jackson D, Ilyas M . Concomitant mutations and splice variants in KRAS and BRAF demonstrate complex perturbation of the Ras/Raf signalling pathway in advanced colorectal cancer. Gut. 2009; 58(9):1234-41. DOI: 10.1136/gut.2008.159137. View

16.

Mu W, Lu H, Chen J, Li S, Elliott A . Sanger Confirmation Is Required to Achieve Optimal Sensitivity and Specificity in Next-Generation Sequencing Panel Testing. J Mol Diagn. 2016; 18(6):923-932. DOI: 10.1016/j.jmoldx.2016.07.006. View

17.

Ahn T, Jeong D, Son M, Jung H, Park S, Kim H . The BRAF mutation is associated with the prognosis in colorectal cancer. J Cancer Res Clin Oncol. 2014; 140(11):1863-71. DOI: 10.1007/s00432-014-1735-y. View

18.

Marchio A, Bertani S, Rojas Rojas T, Doimi F, Terris B, Deharo E . A peculiar mutation spectrum emerging from young peruvian patients with hepatocellular carcinoma. PLoS One. 2014; 9(12):e114912. PMC: 4263719. DOI: 10.1371/journal.pone.0114912. View

19.

Nam S, Yun S, Koh J, Kwak Y, Seo A, Park K . BRAF, PIK3CA, and HER2 Oncogenic Alterations According to KRAS Mutation Status in Advanced Colorectal Cancers with Distant Metastasis. PLoS One. 2016; 11(3):e0151865. PMC: 4798471. DOI: 10.1371/journal.pone.0151865. View

20.

Correa P, Piazuelo M . Helicobacter pylori Infection and Gastric Adenocarcinoma. US Gastroenterol Hepatol Rev. 2011; 7(1):59-64. PMC: 3158605. View