TARGETED microRNA PROFILING IN GASTRIC CANCER
WITH CLINICAL ASSESSEMENT
Pehlevan Ozel H, Dinç T, Tiryaki RS2, Keşkus AG, Konu O, Kayilioglu SI, Coşkun F
*Corresponding Author: Tolga Dinç, M.D., Associate Professor, Department of General Surgery,
Health Sciences University, Ankara City Hospital, Üniversiteler Mahallesi 1604. Cadde No: 9 Çankaya/
Ankara/Turkey. Tel./Fax: +90-312-552-60-00. Intercom: 121514. Mobile: +90-532-481-22-75. Email:
tolga_dr@hotmail.com
page: 55
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RESULTS
Evaluation of Patients’ Demographic, Clinical,
and Pathological Characteristics. In total, 17 (85.0%)
study subjects were men, and three (5.0%) were women;
the mean age was 64.9 ± 13.8 years. Moreover, nine patients
were smokers and five used gastric acid-lowering
drugs. Ten patients had cardiac tumors, while 10 had non
cardiac tumors. Based on the evaluation of the histopathological
examination report of the patients using the tumor
size, lymph node, distant metastasis (TNM) staging
system, 13 patients had T3, and six had T4 tumors, and
only one had a T1 tumor. Based on the evaluation of the
regional lymph nodes, three patients were classified as
N0, while four, seven, and six patients belonged to N1,
N2, and N3, respectively [TNM; American Joint Committee
on Cancer (AJCC), 8th ed.] [25]. There were two
patients who had signet ring cell carcinoma, the subtype of
adenocarcinoma. We found that 18 patients had lymphovascular
invasion, while 14 exhibited nerve invasions in
the tumor. Additional clinical information has been made
available in Table 2. microRNA Expression Changes in the Tumor Tissues
of Patients with Gastric Cancer. Table 3 presents the
miRNA expression changes in cancerous and normal tissues
of the patients, while Table 4 shows the mean changes
observed in the miRNA expression levels in cancerous and
normal tissues, separately, and the statistical significance
of these changes. For the miRNAs hsa-miR-375-3p, hsamiR-
196a-5p, hsa-miR-376c-3p, hsa-miR-129-5p, hsamiR-
34c-5p and hsa-miR-767-5p, a significant decrease
was noted in the cancerous tissues in comparison with the
normal tissues. Overall, the miRNA expression levels were
lower in cancerous tissues than in normal tissues (Figure 1).
In addition, when each miRNA in the individual cancerous
and normal tissue pair was examined, the expressions of
miRNAs were significantly lower.
The cancerous tissues also exhibited lower variability
for hsa-miR-375-3p (p = 0.021), hsa-miR-196a-5p (p =
0.042), hsa-miR-376c-3p (p = 0.023), miR-34c-5p (p =
0.030) and hsa-miR-767-5p (p =.0.038). The narrower
range we observed may indicate the presence of a stronger
genome/transcriptome control (Figure 2).
Association of Tissue microRNA Expression Levels
with the Available Patient Data. Based on the evaluation
of the other known demographic, clinical, and histopathological
characteristics of the patients, an optimal evaluation
could not be made owing to the limited sample size and
the lack of sufficient samples in the subgroups. No significant
result was obtained for variables other than those for
smoking, age, and the number of metastatic lymph nodes
(Table 5 and discussion).
A hierarchical cluster analysis performed using the
changes in the miRNA expressions and the heatmap created by the addition of annotations for smoking status,
age and the number of metastatic lymph nodes, revealed
distinct clusters of miRNAs and patients (Figure 3). For example, miR148a-3p had a relatively different expression
pattern than other miRNAs, while miR-767 and miR-375-
3p in one cluster and miR-196a-5p and miR-123-3p in the
other, showed similar expression profiles. The miRNA
expressions of patients with GCM-01, GCM-03, GCM-04
and GCM-06 code, were different from those of the other
16 patients, and exhibited a decreased expression of miR-
148a-3p, unlike the other patients (Figure 3).
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