Biomarkers for personalized medicine in GI cancers

Zhang, Shuang Yin; Zhang, Shuang Qin; Nagaraju, Ganji Purnachandra; El‐Rayes, Bassel F.

doi:10.1016/j.mam.2015.06.002

Cited by 11 publications

(8 citation statements)

References 170 publications

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“…Once metastasis occurs, more than half of patients die within one year (Shitara et al, 2018). Therefore, the search for prognostic markers of GC is an area of current research interest (Zhang et al, 2015a). In this study, the expression of LBH was confirmed using online datasets and immunohistochemical specimens to predict the prognosis of patients.…”

Section: Discussionmentioning

confidence: 99%

Elevated limb-bud and heart development (LBH) expression indicates poor prognosis and promotes gastric cancer cell proliferation and invasion via upregulating Integrin/FAK/Akt pathway

Zhang

et al. 2019

PeerJ

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The limb-bud and heart development (LBH) gene is a highly conserved, tissue-specific transcription cofactor in vertebrates that regulates multiple key genes in embryonic development. The role of LBH in various cancer types is still controversial, and its specific role and molecular mechanism in the oncogenesis of gastric cancer (GC) remains largely unexplored. In the present study, the prognostic significance and clinicopathological characteristics of LBH in GC was determined. The LBH mRNA expression was first investigated in four independent public datasets (TCGA-STAD, GSE15459, GSE29272, and GSE62254) and then validated with our samples at the protein level. LBH was overexpressed at both the mRNA and protein levels in cancer compared with normal tissues. High LBH expression was correlated with advanced T, N, and M stages. Kaplan–Meier analysis and log-rank test indicated that higher LBH expression was statistically correlated with shorter overall survival (OS) in the public datasets and our study samples. Univariate and multivariate Cox regression analysis showed that LBH was an independent prognostic biomarker for survival in TCGA-STAD, GSE15459, GSE62254 cohorts, and our GC patients. In vitro experiments showed that knockdown of LBH can significantly inhibit the proliferation and invasion of HGC-27 cells, while overexpression of LBH can significantly enhance the proliferation and invasion of BGC-823 cells. Gene Set Enrichment Analysis (GSEA), Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomics (KEGG) indicated that high LBH expression is associated with the PI3K-Akt pathway, focal adhesion, and extracellular matrix (ECM)-receptor interaction. Western blot analysis showed that knockdown of LBH significantly inhibited the expression of integrin α5, integrin β1, p-FAK, and p-Akt. Therefore, results from the present study indicate that LBH is a potential independent prognostic biomarker and promotes proliferation and invasion of GC cells by activating the integrin/FAK/Akt pathway.

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Section: Discussionmentioning

confidence: 99%

Elevated limb-bud and heart development (LBH) expression indicates poor prognosis and promotes gastric cancer cell proliferation and invasion via upregulating Integrin/FAK/Akt pathway

Zhang

et al. 2019

PeerJ

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“…HER‐2 is a proto‐oncogene encoded by the ERBB2 gene, and is a tyrosine kinase receptor belonging to the epidermal growth factor receptor (EGFR) family . It is an important predictive biomarker for GC . HER‐2 testing is recommended in American, European and Asian gastric cancer guidelines in patients with metastatic or recurrent gastric cancer under consideration for palliative chemotherapy.…”

Section: Clinical Presentation Of Gcmentioning

confidence: 99%

“…C‐Met has also been identified as a possible therapeutic target. A third potential biomarker with possible predictive value is the ligand of PD‐1, an immune‐inhibitory receptor of the CD28 family which plays a role in tumour immune escape …”

Section: Clinical Presentation Of Gcmentioning

confidence: 99%

Gastric carcinoma in canines and humans, a review

Hugen

Thomas

German

et al. 2016

Vet Comparative Oncology

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Gastric carcinoma (GC) is the most common neoplasm in the stomach of dogs. Although incidence in the general population is reported to be low, breed-specific GC has a high incidence. Median age at presentation ranges from 8 to approximately 10 years. The disease is mostly located in the lesser curvature and antropyloric region of the stomach. Unfortunately, diagnosis is usually made when the disease is at an advanced stage and, therefore, prognosis is poor. Due to similarities in clinical presentation, diagnosis, histology and prognosis, canine GC may serve as a valuable model for human GC. Extensive pedigrees of canine gastric carcinoma cases could reveal insights for human gastric carcinoma. Putative species differences include the role of Helicobacter in pathogenesis, the wide array of genetic data and screening available for humans, and treatment protocols that are available for human GC.

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“…Although several landmark studies have highlighted the molecular subtypes of GC on DNA, RNA, and protein levels based on large-cohort tumor tissues, the application of such markers in clinical practice remains to be a big challenge 4–6 . Although predictive and resistance markers are equally important for systemic antitumor therapy, most research efforts to date have been focused on exploring the efficacy of predictive markers, while only a few clear markers of resistance have been found 7,8 . Meanwhile, due to the specific features of GC, the current Response Evaluation Criteria in Solid Tumors (RECIST) fail to evaluate drug resistance in a precisely and timely manner 9 .…”

Section: Introductionmentioning

confidence: 99%

Chromosomal instability of circulating tumor DNA reflect therapeutic responses in advanced gastric cancer

et al. 2019

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Gastric cancer is characterized by chromosomal instability. In this study, we investigated chromosomal instability quantified by copy number instability (CNI) score of circulating tumor DNA (ctDNA) during the drug treatment in advanced gastric cancer (AGC). A total of 55 pretherapeutic plasmas from 55 AGC patients and 75 plasmas during drug treatment of 26 AGC patients were collected. Plasma ctDNA was extracted and assessed by whole-genome sequencing (WGS) for somatic copy number alteration (SCNA), and according to which we calculated the CNI scores. We next assessed the correlations between chromosomal instability and therapeutic response. The cutoff value of chromosomal instability was defined as the mean + SD of the CNI scores (56.60) in cfDNA of plasmas from 100 healthy people. For 55 enrolled cases, chromosomal instability was observed in 27 (49%) prior to drug treatment, whose response rate (59%, 16/27) was higher than in 28 patients with stable chromosomes (32%, 9/28, P = 0.043). We also observed that CNI scores fluctuated during treatment in 26 patients. Specifically, the CNI scores in 93% (14/15) of patients sensitive to drug treatment reduced to the level of chromosomal stability and the CNI scores in 52% (13/25) of patients resistant to treatment elevated again. For ctDNA with developed resistance, the SCNA patterns were identical to those before treatment, whereas the CNI scores were lower than the pretherapeutic scores. We found that chromosomal instability based on ctDNA could predict and monitor therapeutic response in gastric cancer, although validation in a larger cohort will be necessary.

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Biomarkers for personalized medicine in GI cancers

Cited by 11 publications

References 170 publications

Elevated limb-bud and heart development (LBH) expression indicates poor prognosis and promotes gastric cancer cell proliferation and invasion via upregulating Integrin/FAK/Akt pathway

Elevated limb-bud and heart development (LBH) expression indicates poor prognosis and promotes gastric cancer cell proliferation and invasion via upregulating Integrin/FAK/Akt pathway

Gastric carcinoma in canines and humans, a review

Chromosomal instability of circulating tumor DNA reflect therapeutic responses in advanced gastric cancer

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