Tumor Biology - Volume 45, issue 1

Authors: Alshehri, Eman | Al-Dogmi, Amal M. | Al-Hazani, Tahani Mohamed Ibrahim | Alwaili, Maha Abdulla | Safhi, Fatmah Ahmed | Alneghery, Lina Mohammed | Jalal, Areej Saud | Alanazi, Ibtesam Sanad | AlQassim, Fatima Abdullah | Alhumaidi Alotaibi, Mashael | Al-Qahtani, Wedad Saeed

Article Type: Research Article

Abstract: BACKGROUND: Smoking is one of the most popular risk factors provoking bladder cancer (BC). This research intended to estimate cigarette smoking effect involving PAF signs between smoking patients with BC and non-smoking patients with same diagnosis to define relations with pathological characteristics and their prognosis on zero-relapse and disease-associated recovery. METHODS: Two groups of smokers (n  = 54) and non-smokers (n  = 62) were selected. Both cohorts of patients had BC. They were evaluated utilizing NGS on 9 cancer-related genes and confirmed through the Sanger DNA sequencing and histopathological tests based on H&E staining. The factor of smoking and impact …of PAF development by ELISA assay and PAF-R manifestation in terms of immunochemical evaluation on BC areas comparing to a control group (n  = 30) was examined involving healthy contributors, including the use of well-designed statistical trials. RESULTS: The multivariate evaluation showed considerable rise in mutation patterns related to smoking among BC patients (group 3), increase in PAF development (***P<0.001) and vivid signs of PAF-R contrasted to non-smokers with BC (group 2) and control group (group 1). All the identified biological changes (gains/losses) were recorded at the same locations in both groups. Patients from group 3 held 3-4 various mutations, while patients from group 2 held 1-3 various mutations. Mutations were not identified in 30 respondents from control group. The most repeated mutations were identified in 3 of 9 examined genes, namely TP53, PIK3CA and PTEN, with highest rates of increase in Group 3. Moreover, histopathological tests revealed barely identifiable and abnormal traits in BC tissues, i.e. were without essential histopathological changes between groups 2 and 3. CONCLUSION: Smoking of cigarettes provokes PAF development due to urothelial inflammation and rise of mutations in 9 cancer-related genes. These are indicative factors of inducing BC. Show more

Keywords: Cigarette smoking, 9 cancer-associated genes, somatic mutations, platelet-activating factor (PAF), bladder cancer patients

DOI: 10.3233/TUB-220032

Citation: Tumor Biology, vol. 45, no. 1, pp. 1-14, 2023

Authors: Sánchez-López, Josefina Yoaly | Vázquez-Ibarra, Katia Carolina | García-Muro, Andrea Marlene | García-Ruvalcaba, Azaria | Pacheco-Sotelo, Sergio | Díaz-Herrera, Luis Carlos | Marin-Contreras, Marıa Eugenia

Article Type: Research Article

Abstract: BACKGROUND: A 100-bp insertion/deletion polymorphism in the pepsinogen C gene has been associated with the risk of gastric cancer (GC). OBJECTIVE: We analyzed the relationships of the 100-bp insertion/deletion polymorphism with GC, atrophic gastritis (AG), and intestinal metaplasia (IM) in the Mexican general population (MGP). METHODS: We studied the genomic DNA of subjects with GC n  = 80, AG and IM n  = 60, controls n  = 110, and the MGP n  = 97. PGC gene insertion/deletion polymorphism was identified by means of PCR, capillary electrophoresis and GeneScan software. RESULTS: Different allele sizes of PGC polymorphism were observed …in the studied groups, from 266 bp to 499 bp, which were grouped for the analysis as short alleles of 266–399 bp, medium alleles of 400–433 bp and large alleles of 434–499 bp. Carriers of one or two medium alleles, had an increased risk of GC, with OR of 1.99 (CI95% 1.08–3.67 p  = 0.026) compared to homozygotes (no medium/no medium). CONCLUSIONS: Previous studies have related PGC short alleles to risk for or protection against GC depending on the ethnic origin of the population. In our study, medium alleles were related to risk for GC. Further studies are required to establish the importance of this polymorphism in the origin of gastric neoplasia. Show more

Keywords: Gastric cancer, polymorphisms, neoplasia

DOI: 10.3233/TUB-220025

Citation: Tumor Biology, vol. 45, no. 1, pp. 15-21, 2023

Authors: Mokarizadeh, Aram

Article Type: Article Commentary

DOI: 10.3233/TUB-220031

Citation: Tumor Biology, vol. 45, no. 1, pp. 23-24, 2023

Article Type: Retraction

DOI: 10.3233/TUB-239005

Citation: Tumor Biology, vol. 45, no. 1, pp. 25-25, 2023

Article Type: Retraction

DOI: 10.3233/TUB-239006

Citation: Tumor Biology, vol. 45, no. 1, pp. 27-27, 2023

Article Type: Retraction

DOI: 10.3233/TUB-239007

Citation: Tumor Biology, vol. 45, no. 1, pp. 29-29, 2023

Authors: Jeethy Ram, T. | Lekshmi, Asha | Darvin, Pramod | Rajappan, Prakash | Jagathnath Krishna, K.M. | Anoop, T.M. | Augustine, Paul | Mathew, Arun Peter | Cherian, Kurian | Bhargavan, Rexeena V. | Somanathan, Thara | Radhakrishna Pillai, M. | Santhosh Kumar, T.R. | Sujathan, K.

Article Type: Research Article

Abstract: BACKGROUND: Lack of druggable targets and complex expression heterogeneity of known targets is common among TNBC subtypes. An enhanced expression of galectin-3 in TNBCs has already been documented. We have observed a tumor progression-dependent galectin-3 expression in TNBCs compared to adjacent epithelium and non TNBCs. OBJECTIVE: To unravel the association of galectin- 3 in tumor progression, aggressiveness and drug resistance in TNBC patients. METHODS: Galectin-3 expression in 489 breast cancer tissues was correlated with clinicopathological features and the results were validated in cell lines and mouse model by silencing galectin-3 using shRNA and the proteins were …profiled by western blot and qRT-PCR. Protein interaction was analyzed by GFP Trap and Mass spectrometry. RESULTS: Galectin-3 expression correlated with tumor stage in TNBC and a lower galectin-3 expression was associated with poor patient survival. The positive correlation between galectin-3, vimentin and CD44 expression, pinpoints galectin-3 contribution to epithelial to mesenchymal transition, drug resistance and stemness. Vimentin was found as an interacting partner of galectin-3. Duplexing of galecin-3 and vimentin in patient samples revealed the presence of tumor cells co-expressing both galectin-3 and vimentin. In vitro studies also showed its role in tumor cell survival and metastatic potential, elementary for tumor progression. In vivo studies further confirmed its metastatic potential. CONCLUSIONS: Tumor progression dependent expression pattern of galectin 3 was found to indicate prognosis. Co-expression of galectin-3 and vimentin in tumor cells promotes tumor dissemination, survival and its metastatic capability in TNBCs. Show more

Keywords: Epithelial mesenchymal transition, galectin-3, vimentin, metastasis, chemoresistance, tumor survival

DOI: 10.3233/TUB-230002

Citation: Tumor Biology, vol. 45, no. 1, pp. 31-54, 2023

Authors: Ghosh, Abhisikta | Ghosh, Arnab | Sinha, Abarna | Mathai, Sonia | Bhaumik, Jaydip | Mukhopadhyay, Asima | Maitra, Arindam | Biswas, Nidhan K. | Majumder, Partha P. | Sengupta, Sharmila

Article Type: Research Article

Abstract: BACKGROUND: Cervical cancers (CaCx), like many other cancer types, portray high molecular heterogeneity that affects response to therapy, including immunotherapy. In India and other developing countries, CaCx mortality rates are very high because women report to the clinics with advanced cancers in absence of organized screening programs. This calls for implementation of newer therapeutic regimens for CaCx, like immunotherapy, which is again not used commonly in such countries. OBJECTIVE: Therefore, we focused on dissecting tumour immune heterogeneity, if any, identify immune gene-based biomarkers of heterogeneity and subsets of such cancers with the potential for immunotherapy. We also attempted …to characterize the cancer-associated phenotypes of such subsets, including viral load, to decipher the relationship of tumour immunogenicity with oncogenicity. METHODS: Employing RNA-seq analysis of 44 HPV16 positive CaCx patients, immune subtypes were identified by unsupervised hierarchical clustering of global immune-gene expression profiles. Proportions of tumor infiltrating immune cells in the tumor milieu were estimated, employing Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT), using gene expression data from RNA-seq. The oncogenic phenotypes of the immune subtypes of CaCx were deciphered through differential gene expression (DEGs) and pathway enrichment analysis. Viral load was estimated through TaqMan-based qRT-PCR analysis. RESULTS: Analysis revealed the presence of two immune subtypes of CaCx, A (26/44; 59.09%) and B (18/44; 40.90%). Compared to Subtype-A, Subtype-B portrayed overexpression of immune genes and high infiltration of immune cells, specifically CD8+ T cells (p  < 0.0001). Besides, a significant correlation between PD-1 and PD-L1 co-expression among Subtype-B, as opposed to Subtype-A, confirmed the interactive roles of these immune checkpoint molecules in Subtype B. Stepwise discriminant analysis pin-pointed ten immune-genes that could classify 100% of the patients significantly (p  < 0.0001) into the two immune subtypes and serve as potential biomarkers of CaCx immunity. Differential gene expression analysis between the subtypes unveiled that Subtype-B was more biologically aggressive than Subtype-A, reflecting loss of structural integrity and promotion of cancer progression. The viral load was significantly lower in Subtype-B (average viral load = 10.74/100 ng of genomic DNA) compared to Subtype-A (average viral load = 14.29/100 ng of genomic DNA). Thus viral load and the ten-gene panel underscore their association with immunogenicity and oncogenicity. CONCLUSION: Our study provides strong evidence that only a subset, about 41% of HPV16 positive CaCx patients in India, portray immune enrichment of the tumor milieu coupled with aggressive phenotypes. Such subtypes are therefore likely to benefit through checkpoint molecule-based or tumor infiltrating lymphocyte-based immunotherapy, which could be a leap forward in tackling aggressive forms of such CaCx in India and other developing countries. Show more

Keywords: Cervical cancer, stepwise discriminant analysis, immune subtypes, oncogenic phenotypes, HPV16 load

DOI: 10.3233/TUB-220035

Citation: Tumor Biology, vol. 45, no. 1, pp. 55-69, 2023

Article Type: Retraction

DOI: 10.3233/TUB-239008

Citation: Tumor Biology, vol. 45, no. 1, pp. 71-71, 2023

Authors: Fan, Frank S.

Article Type: Article Commentary

Abstract: Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to low-density lipoprotein (LDL) receptor and fatty acid translocase CD36, inducing lysosomal degradation of these two receptors in the liver cells. Both monoclonal antibody (mAb) and small-interfering RNA (siRNA) targeting PCSK9 have been designed for treatment of familial hypercholesterolemia recently, with elevating LDL receptors on the liver cell surface and increasing LDL uptake as the main beneficial mechanism. However, given that the binding domains of PCSK9 for LDL receptor and CD36 are different, and PCSK9 mAb only attacks the domain for LDL receptor, CD36 expression remains partially controlled under PCSK9 mAb treatment. In …contrast, PCSK9 siRNA brings on complete loss of PCSK9, resulting in overexpression of CD36. Based on the fact that CD36 is a key factor in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) and subsequent hepatocellular carcinoma (HCC), the risk of developing NAFLD and HCC on long-term use of PCSK9 siRNA is thus raised as a hypothesis. Additionally, because CD36 is also involved in the promotion of malignant diseases other than HCC, such as acute myeloid leukemia, gastric cancer, breast cancer, and colorectal cancer, the speculative danger of flourishing these malignancies by PCSK9 siRNA is discussed as well. Show more

Keywords: Fatty acid translocase CD36, hepatocellular carcinoma, non-alcoholic fatty liver disease, proprotein convertase subtilisin/kexin type 9, small-interfering RNA

DOI: 10.3233/TUB-230007

Citation: Tumor Biology, vol. 45, no. 1, pp. 73-80, 2023