Circular RNA hsa_circ_0007507 May Serve as a Biomarker for the Diagnosis and Prognosis of Gastric Cancer

Abstract

PurposeThe morbidity and mortality of gastric cancer (GC) remain high worldwide. In recent years, circular RNAs (circRNAs) have attracted widespread attention among cancer researchers due to the stable ring structure. The present work aims to find serum circRNA biomarkers that can be used in clinical applications and effective diagnosis.MethodsHsa_circ_0007507 was extracted through circRNA sequencing. Exonuclease digestion assay, actinomycin D, agarose gel electrophoresis (AGE), and Sanger sequencing verified the potential of hsa_circ_0007507 as a biomarker. Besides, a real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) was established to detect the level of expression of hsa_circ_0007507. Twenty cases of GC and the paired adjacent tissues were collected to verify its overexpression. Then, serum samples from 30 cases of colorectal cancer, 30 cases of thyroid cancer, and 30 cases of breast cancer were collected to verify their organ specificity. Additionally, serum samples from 80 healthy people, 62 gastritis patients, 31 intestinal metaplasia patients, and 100 GC patients were collected, and the diagnostic efficacy was evaluated through analysis of the receiver operating characteristic (ROC) curve. Furthermore, 16 post-operative GC samples, samples of 65 relapsed patients and 36 non-relapsed patients were collected to evaluate the prognosis of GC.ResultsThe level of expression of hsa_circ_0007507 in GC tissues was up-regulated (p = 0.0121), which was consistent with the results of circRNA sequencing. Exonuclease digestion assay and actinomycin D confirmed that hsa_circ_0007507 had a stable structure and a longer half-life. In the analysis of organ specificity experiments, serum hsa_circ_0007507 did not have specificity for patients with colorectal cancer (p = 0.5319), thyroid cancer (p = 0.5422), or breast cancer (p = 0.5178). Analysis of diagnostic efficacy indicated that the expression of hsa_circ_0007507 was significantly higher than that of normal people (p <0.0001); the area under the ROC (AUC) was 0.832 (95% CI: 0.771-0.892); the diagnostic power of hsa_circ_0007507 was higher than that of CEA (AUC = 0.765, 95% CI: 0.697-0.833) and CA199 (AUC = 0.587, 95% CI: 0.504-0.67). Through diagnosis using a combination of the three, GC patients could be distinguished from normal people (AUC = 0.849), and higher diagnostic efficiency could be achieved. The expression of serum hsa_circ_0007507 in GC patients significantly decreased after surgery (p = 0.001). Besides, the expression of serum hsa_circ_0007507 in patients with post-operative recurrence was significantly up-regulated again (p = 0.0139).ConclusionsSerum hsa_circ_0007507 is differentially expressed in GC patients, post-operative GC patients, gastritis patients, intestinal metaplasia patients and relapsed patients, suggesting that serum hsa_circ_0007507 can be used as a new diagnostic and dynamic monitoring biomarker for GC.

circ_0006089 promotes gastric cancer growth, metastasis, glycolysis, and angiogenesis by regulating miR‐361‐3p/TGFB1

“…Many circRNAs have been confirmed to participate in GC malignant progression. circ_0007505 was found to be an upregulated circRNA and it might be a potential treatment target for GC 13 . Also, circ_0006470 was considered to be an oncogene in GC that enhanced GC proliferation and migration through the miR‐27b‐3p/PI3KCA pathway 14 .…”

“…circ_0007505 was found to be an upregulated circRNA and it might be a potential treatment target for GC. 13 Also, circ_0006470 was considered to be an oncogene in GC that enhanced GC proliferation and migration through the miR‐27b‐3p/PI3KCA pathway. 14 Additionally, circPTK2 has been discovered to act as an miR‐196‐3p sponge to upregulate AATK, thereby inhibiting GC proliferation and metastasis.…”

Comprehensive Analysis of circRNA Expression Profiles in Human Brown Adipose Tissue

“… 31–33 In addition, hsa_circRNA_0007507 and its host gene, RASA1, are upregulated in gastric cancer. 34 …”

Circular RNAs as diagnostic biomarkers for gastric cancer: A comprehensive update from emerging functions to clinical significances

“…Further in vivo investigations verified that the combination treatment of circUBE2Q2 knockdown and STAT3 inhibitor had synergistic effects on the inhibition of gastric cancer growth, suggesting that targeting circUBE2Q2 may increase the sensitivity of targeted therapies to gastric cancer ( Yang et al, 2021b ) ( Figure 3B ). In addition, the differential expression of serum hsa_circ_0007507 among GC, post-operative GC, gastritis, intestinal metaplasia and relapsed patients, suggests it would be useful as a new diagnostic and dynamic monitoring biomarker for GC ( Zhang et al, 2021 ) ( Figure 3C ). More specifically, the study of Li et al (2017a) showed that hsa_circ_0000096 was significantly downregulated in gastric cancer tissues ( p < 0.001) and the AUC was as high as 0.82, indicating high diagnostic accuracy.…”