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. 2022 Jul 13:12:919351.
doi: 10.3389/fonc.2022.919351. eCollection 2022.

Telomere Attrition With Concomitant hTERT Overexpression Involved in the Progression of Gastric Cancer May Have Prognostic and Clinical Implications in High-Risk Population Group From North India

Ifra Mushtaq  1 , Gh Rasool Bhat  1 , Bilal Rah  1 , Syed Besina  2 , Sheikh Zahoor  3 , Muneer A Wani  4 , Mubashir A Shah  4 , Sadaf Bashir  1 , Muzamil Farooq  1 , Rafiq A Rather  1 , Dil Afroze  1
Affiliations

Telomere Attrition With Concomitant hTERT Overexpression Involved in the Progression of Gastric Cancer May Have Prognostic and Clinical Implications in High-Risk Population Group From North India

Ifra Mushtaq et al. Front Oncol. .

Abstract

Genetic instabilities exacerbated by the dysfunction of telomeres can lead to the development of cancer. Nearly 90% of all human malignancies are linked with telomere dysregulation and overexpression of telomerase, an enzyme that catalyzes the synthesis of telomeric DNA repeats at the ends of chromosomes. The burden of gastric cancer continues to inflict a deterring impact on the global health scenario, accounting for over one million new cases in 2020. The disease is asymptomatic in its early stages of progression, which is attributed to the poor prognosis and overall surge in mortality rate worldwide. Exploiting telomere physiology can provide extensive mechanistic insight into telomere-associated gastric cancer progression and its use as a target in a variety of therapeutic interventions. In this study, we aimed to evaluate the clinical implications of c-Myc, human telomerase reverse transcriptase (hTERT) expression, and telomere length in patients with gastric cancer. A total of 57 gastric cancer cases and adjacent controls were included in the study. RT-PCR and immunohistochemistry were used to assess the expression levels of c-Myc and hTERT. The relative telomere length was measured by MMQPCR using the Cawthon method. Our results indicated that the shorter telomere and increased hTERT expression were associated with gastric cancer progression. The study also highlighted the role of short telomeres and increased expression of hTERT in gastric cancer progression and its association with various etiological risk factors, transcriptional activators, and overall survival among the ethnic Kashmiri population of North India.

Keywords: North India; c-Myc; gastric cancer (GC); human telomerase reverse transcriptase (hTERT); telomeres.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Upregulation of c-Myc expression in gastric cancer. (A) Tissue. (B) Blood. (C) Stage III compared to stages I and II.
Figure 2
Figure 2
Increased expression of hTERT in gastric cancer. (A) Tissue. (B) Blood. (C) Late stage. and (D) Advanced age.
Figure 3
Figure 3
(A) Representative images of immunohistochemistry (IHC) of c-Myc in (A) stage I, (B) stage II, and (C) stage III. (B) Representative images of immunohistochemistry (IHC) of hTERT in (A) stage I, (B) stage II, and (C) stage III.
Figure 4
Figure 4
(A) Relative telomere length among cases and controls. (B) Advanced age. (C) Males compared to females. (D) Smokers compared to nonsmokers.
Figure 5
Figure 5
The Kaplan–Meier survival plot depicts (A) overall survival (OS) in gastric cancer patients; (B) overall survival (OS) in different stages; (C, D) association of overall survival (OS) with c-Myc expression and hTERT expression; and (E) association of overall survival (OS) with relative telomere length.
Figure 6
Figure 6
The heat map plot of hTERT and c-Myc expression. Columns of the plot represent the genes and the rows represent samples, respectively.
Figure 7
Figure 7
Interaction of hTERT and c-Myc genes with other critical genes using various networks. Each color represents a different type of interaction and its role in various biological processes.
Figure 8
Figure 8
Progression of gastric carcinoma is mediated by the binding of oncogene c-Myc to the hTERT promoter region via transcription factor domains MAD/MAX complex, resulting in upregulation of hTERT, which in turn causes the repeated synthesis of telomeric DNA and drives the cell toward tumorigenesis.
See this image and copyright information in PMC

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