Browsing by Author "Monika Rajput"

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A Novel Jak1 Gene Mutation in Invasive Breast Carcinoma
(John Wiley and Sons Inc, 2025) Paras Kumar; Monika Rajput; Manoj Pandey
[No abstract available]
Antisense RNAs (asRNAs) as key players in gallbladder cancer progression: a bioinformatics analysis
(Research Institute for Gastroenterology and Liver Diseases, 2025) Monika Rajput; Ruhi Dixit; Manoj Pandey; Vijay Kumar Shukla
Aim: This study reports differential expression of Antisense RNAs (asRNAs) by analyzing transcriptomic profiles in gallbladder cancer (GBC). Background: asRNAs play crucial roles in developing various tumors. However, the presence and biological mechanism of asRNAs in GBC development are still unknown. Methods: Differentially expressed asRNAs (DE-asRNAs) were systematically identified from RNA sequencing data \ from ten GBC patients. Functional enrichment analysis was performed, followed by the identification of mRNAs targeted by asRNAs and the construction of a gene regulatory network of asRNAs targeting mRNAs. Results: Of the 891 asRNAs identified, 17 DE-asRNAs were statistically significant. Out of 17, 12 asRNAs were upregulated, and five asRNAs were downregulated. Functional enrichment analysis showed their role in methylation and developmental processes. Of the 17 asRNAs, 14 are novel (UNC5B-AS1, SLC2A1-AS1, BBOX1-AS1, SOX21-AS1, ELFN1-AS1, TRPM2-AS, DNAH17-AS1, DCST1AS1, VPS9D1-AS1, MIR1-1HG-AS1, HAND2-AS1, PGM5P4-AS1, PGM5P3-AS1, and MAGI2-AS). Enrichment analysis of asRNAs with target mRNAs showed enrichment in biological regulation and developmental processes involved in the PI3K, p53, apoptosis, and VEGF signaling pathways. Conclusion: This study identified 14 asRNAs for the first time and showed that asRNAs targeting mRNAs strongly associated with tumor development in GBC through the PI3KCA and TP53 pathways. © 2025, Gastroenterology and Hepatology From Bed to Bench (GHFBB). This is an open-access article, distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by nc/4.0/) which permits others to copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.
Aspirin and Cancer Survival: An Analysis of Molecular Mechanisms
(Multidisciplinary Digital Publishing Institute (MDPI), 2024) Manoj Pandey; Monika Rajput; Pooja Singh; Mridula Shukla; Bin Zhu; Jill Koshiol
The benefit of aspirin on cancer survival is debated. Data from randomized clinical trials and cohort studies are discordant, although a meta-analysis shows a clear survival advantage when aspirin is added to the standard of care. However, the mechanism by which aspirin improves cancer survival is not clear. A PubMed search was carried out to identify articles reporting genes and pathways that are associated with aspirin and cancer survival. Gene ontology and pathway enrichment analysis was carried out using web-based tools. Gene–gene and protein–protein interactions were evaluated. Crosstalk between pathways was identified and plotted. Forty-one genes were identified and classified into primary genes (PTGS2 and PTGES2), genes regulating cellular proliferation, interleukin and cytokine genes, and DNA repair genes. The network analysis showed a rich gene–gene and protein–protein interaction between these genes and proteins. Pathway enrichment showed the interleukin and cellular transduction pathways as the main pathways involved in aspirin-related survival, in addition to DNA repair, autophagy, extracellular matrix, and apoptosis pathways. Crosstalk of PTGS2 with EGFR, JAK/AKT, TP53, interleukin/TNFα/NFκB, GSK3B/BRCA/PARP, CXCR/MUC1, and WNT/CTNNB pathways was identified. The results of the present study demonstrate that aspirin improves cancer survival by the interplay of 41 genes through a complex mechanism. PTGS2 is the primary target of aspirin and impacts cancer survival through six primary pathways: the interleukin pathway, extracellular matrix pathway, signal transduction pathway, apoptosis pathway, autophagy pathway, and DNA repair pathway. © 2024 by the authors.
Efficacy and safety of cetuximab-based versus platinum-based chemoradiation in HNSCC: evidence from a meta-analysis of 10 randomized controlled trials
(Springer Science and Business Media Deutschland GmbH, 2025) Tarun Kumar; Nishu Kesh; Atindra Kumar Pandey; Ankita Chakrawal; Bhavana Singh; Manjusha Pal; Monika Rajput; Ruhi Dixit; Esha Pai; Manoj Pandey
Background: Platinum-based chemoradiotherapy (CTRT) is the standard treatment for head and neck squamous cell carcinoma (HNSCC). While cetuximab-based radiotherapy (CxRT) has been proposed as an alternative, its efficacy remains controversial. Multiple meta-analyses have compared CxRT with CTRT for HNSCC though they combined randomized controlled trials (RCTs) with lower-evidence studies, compromising result validity. This study presents the first meta-analysis using exclusively RCT data, providing the highest level of evidence for clinical decision-making. Methods: We systematically searched MEDLINE, Embase, Cochrane, and SCOPUS, identifying 10 RCTs (n = 2,557 patients). Primary outcomes included overall survival (OS), disease-free survival (DFS), and all-cause mortality; secondary outcomes were Grade ≥ 3 toxicities. Hazard ratios (HRs) and odds ratios (ORs) were pooled using random effect models. Results: CxRT was associated with a 50% higher recurrence risk (HR 1.50, 95% CI 1.07–2.10) and 27% increased all-cause mortality (OR 1.27, 95% CI 1.05–1.55) compared to CTRT. OS did not differ significantly (HR 1.33, 95% CI 0.79–2.22). Toxicity profiles varied: CxRT had higher mucositis (OR 1.17, 95% CI 1.04–1.32) and skin rash (OR 3.46, 95% CI 1.28–9.36), while CTRT showed more anemia (OR 0.15, 95% CI 0.05–0.52) and nausea/vomiting (OR 0.31, 95% CI 0.19–0.53). Conclusion: CxRT is inferior to CTRT in HNSCC, with poorer disease control and survival outcomes. The lack of biomarker (EGFR/RAS) stratification in trials may have contributed to suboptimal patient selection. While CxRT may be an option for cisplatin-ineligible patients, platinum-based therapy appears to be the standard. Future research should optimize cetuximab’s role through biomarker-driven selection. © The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO) 2025.
Evidence to Support the Collaboration of SP1, MYC, and HIF1A and Their Association with microRNAs
(Multidisciplinary Digital Publishing Institute (MDPI), 2024) Jong Ho Chun; Kotohiko Kimura; Monika Rajput; Ming-Hua Hsu; Yu-Chuan Liang; Akanksha Ramadas Shanbhag; Pei-Ju Chiang; Tiffany L. B. Jackson; Ru Chih C. Huang
This study provides evidence to support the concept proposed by Kimura et al. in 2023 that the inhibitors of SP1, MYC, and HIF1A should induce strong anticancer activity by reducing the expression of stem cell-related proteins. In LN229 and U87MG glioblastoma cells, either tetra-methyl-O-nordihydroguaiaretic acid (M4N) or tetra-acetyl-O-nordihydroguaiaretic acid (A4N) suppressed SP1 and only a few stem cell-related proteins and induced only a small amount of cell death; in contrast, the combination treatment of M4N with A4N greatly suppressed the expression of SP1, MYC, and HIF1A, as well as all of the stem cell-related proteins examined, and greatly induced cell death. The bioinformatic analysis showed that the proteins associated with SP1, MYC, and HIF1A were specifically involved in the regulation of transcription and that various microRNAs (miRNAs) that had been shown to induce either anti- or procancer activity were associated with SP1, MYC, and HIF1A, which suggested that the inhibition of SP1, MYC, and HIF1A could modulate the transcription of both coding and noncoding RNAs and affect cancers. These data overall supported our concept. © 2024 by the authors.
Human long non-coding RNAs acquired from bacteria via horizontal gene transfer promote gallbladder cancer
(Springer Science and Business Media B.V., 2025) Manoj Pandey; Monika Rajput; Pooja Singh; Vijay Kumar Shukla; Ruhi Dixit
Background: Gallbladder cancer, the most common malignancy of the bile duct, has a poorly understood etiopathogenesis. Non-coding RNAs are implicated in various cancers, but their role in gallbladder carcinogenesis remains unclear. Methods: Transcriptomic data from gallbladder cancer patients were analyzed to identify differentially expressed long non-coding RNAs (lncRNAs). These data underwent cross-species phylogenetic analysis and BLAST comparison with bacterial and ancient human genomes, including Homo heidelbergensis and Homo neanderthalensis. Pathway analysis, gene-gene interactions, and data and text mining were performed for non-conserved, non-coding genes. Results: Of 16 differentially expressed lncRNAs, seven showed phylogenetic links to bacterial genomes, suggesting acquisition through horizontal gene transfer (HGT) during human evolution. These lncRNAs were present in ancient human species with sequence variations. Functional analysis revealed their role in regulating biological and genetic processes, potentially promoting gallbladder carcinogenesis. Conclusions: This is the first study to propose that seven human lncRNAs, likely of bacterial origin, were acquired through HGT during evolution. These lncRNAs regulate transcriptional and post-transcriptional processes, potentially inducing gallbladder carcinogenesis, thus highlighting a novel link between evolutionary genetics and cancer. © The Author(s), under exclusive licence to Springer Nature B.V. 2025.
Identification of key genes and construction of regulatory network for the progression of cervical cancer
(Elsevier Inc., 2020) Monika Rajput; Mukesh Kumar; Mayuri Kumari; Atanu Bhattacharjee; Aanchal Anant Awasthi
Across the globe, cervical cancer is the fourth main cause of cancer-associated deaths in women. The present study aimed to identify the differentially expressed genes (DEGs) and enriched pathways involved in cervical cancer. From the database, Gene Expression Omnibus (GEO) microarray data of 300 patients with cervical cancer (GSE44001) was used for analysis purposes. Statistical analysis was performed to identify DEGs between different stages of cervical cancer and progression, and a total of 36 common DEGs were screened. The Gene ontology analysis (GO) and protein-protein interaction (PPI) network were used to find relationship among the DEGs. The gene-miRNA interaction networks were constructed by NetworkAnalyst software. The study revealed that various DEGs are involved in the process of oncogeneis. Genes like TP63, IGF1, AIM2, ABCB7, ARHGAP6, RAP2B, HIST1H3C, THOC2, TRIM66, PKN3, CNBP & ATG3 may play a crucial role in cervical cancer. DEGs like THCO2, TAF5L, GPS1, PKN3 & VPSI3A are upregulated. The down regulated DEGs are KHL13, ST8IA4, RAP2B, FRMD8, EGL6, KLHDC10, TRIM66 & CNBP. Based on the investigation, miRNAs and associated DEGs were analyzed, which in turn helped us in a better understanding of the prognosis of cervical cancer. Comprehensively our results revealed the potential use of biomarkers in the diagnosis of cervical cancer and may uplift the development of advanced cervical cancer therapy and treatment of cancer. © 2020
Is cross-species horizontal gene transfer responsible for gallbladder carcinogenesis
(BioMed Central Ltd, 2024) Monika Rajput; Manoj Pandey; Ruhi Dixit; Vijay K. Shukla
Background: Cross-species horizontal gene transfer (HGT) involves the transfer of genetic material between different species of organisms. In recent years, mounting evidence has emerged that cross-species HGT does take place and may play a role in the development and progression of diseases. Methods: Transcriptomic data obtained from patients with gallbladder cancer (GBC) was assessed for the differential expression of antisense RNAs (asRNAs). The Basic Local Alignment Search Tool (BLAST) was used for cross-species analysis with viral, bacterial, fungal, and ancient human genomes to elucidate the evolutionary cross species origins of these differential asRNAs. Functional enrichment analysis and text mining were conducted and a network of asRNAs targeting mRNAs was constructed to understand the function of differential asRNAs better. Results: A total of 17 differentially expressed antisense RNAs (asRNAs) were identified in gallbladder cancer tissue compared to that of normal gallbladder. BLAST analysis of 15 of these asRNAs (AFAP1-AS1, HMGA2-AS1, MNX1-AS1, SLC2A1-AS1, BBOX1-AS1, ELFN1-AS1, TRPM2-AS, DNAH17-AS1, DCST1-AS1, VPS9D1-AS1, MIR1-1HG-AS1, HAND2-AS1, PGM5P4-AS1, PGM5P3-AS1, and MAGI2-AS) showed varying degree of similarities with bacterial and viral genomes, except for UNC5B-AS1 and SOX21-AS1, which were conserved during evolution. Two of these 15 asRNAs, (VPS9D1-AS1 and SLC2A1-AS1) exhibited a high degree of similarity with viral genomes (Chikungunya virus, Human immunodeficiency virus 1, Stealth virus 1, and Zika virus) and bacterial genomes including (Staphylococcus sp., Bradyrhizobium sp., Pasteurella multocida sp., and, Klebsiella pneumoniae sp.), indicating potential HGT during evolution. Conclusion: The results provide novel evidence supporting the hypothesis that differentially expressed asRNAs in GBC exhibit varying sequence similarity with bacterial, viral, and ancient human genomes, indicating a potential shared evolutionary origin. These non-coding genes are enriched with methylation and were found to be associated with cancer-related pathways, including the P53 and PI3K-AKT signaling pathways, suggesting their possible involvement in tumor development. © The Author(s) 2024.
MAP kinase and mammalian target of rapamycin are main pathways of gallbladder carcinogenesis: results from bioinformatic analysis of next generation sequencing data from a hospital-based cohort (NCT05404347)
(Springer Science and Business Media B.V., 2022) Monika Rajput; Satyavjiay Chigurupati; Roli Purwar; Mridula Shukla; Manoj Pandey
Background: Gallbladder Cancer (GBC) is one of the most common cancers of the biliary tract and the third commonest gastrointestinal (GI) malignancy worldwide. The disease is characterized by the late presentation and poor outcome despite treatment, and hence, newer therapies and targets need to be identified. Methods: The current study investigated various functionally enriched pathways in GBC pathogenesis involving the genes identified through Next Generation Sequencing (NGS) in a hospital-based cohort. The Pathway enrichment analysis and Gene Ontology (GO) were carried out after NGS, followed by the construction of the protein–protein interaction (PPI) network to discover associations among the genes. Results: Of the thirty-three patients with GBC who were screened through next-generation sequencing (NGS), 27somatic mutations were identified. These mutations involved a total of 14 genes. The p53 and KRAS were commonly found to be mutated, while mutations in other genes were seen in one case each, the mean number of mutations were 1.2, and maximum mutation in a single case (eight) was seen in one case. The bioinformatics analysis identified MAP kinase, PI3K-AKT, EGF/EGFR, and Focal Adhesion PI3K-AKT-mTOR signaling pathways and cross-talk between these. Conclusion: The results suggest that the complex crosstalk between the mTOR, MAPK, and multiple interacting cell signaling cascades can promote GBC progression, and hence, mTOR–MAPK targeted treatment will be an attractive option. © 2022, The Author(s), under exclusive licence to Springer Nature B.V.
Novel mutations in a second primary gastric cancer in a patient treated for primary colon cancer
(BioMed Central Ltd, 2023) Roli Purwar; Madhumita Tripathi; Monika Rajput; Manjusha Pal; Manoj Pandey
A 60-year-old man presented with complaints of abdominal pain and melena. Patient had a history of colon cancer 16 years back and had undergone right hemi colectomy for microsatellite instability (MSI) negative, mismatch repair (MMR) stable, T2N0 disease with no mutations on next-generation sequencing (NGS). Investigations revealed a second primary in stomach (intestinal type of adenocarcinoma) with no recurrent lesions in colon or distant metastasis. He was started on CapOx with Bevacizumab and developed gastric outlet obstruction. Total gastrectomy with D2 lymphadenectomy and Roux-en-Y oesophageao-jejunal pouch anastomosis was done. The histopathology showed intestinal type of adenocarcinoma with pT3N2 disease. NGS showed 3 novel mutations in KMT2A, LTK, and MST1R gene. The pathway enrichment analysis and Gene Ontology were carried out, followed by the construction of protein–protein interaction network to discover associations among the genes. The results suggested that these mutations have not been reported in gastric cancer earlier and despite not having a direct pathway of carcinogenesis they probably act through modulation of host of miRNA’s. Further studies are needed to investigate the role of KMT2A, LTK, and MST1R gene in gastric carcinogenesis. © 2023, The Author(s).
Tumor hypoxia and role of hypoxia-inducible factor in oral cancer
(BioMed Central Ltd, 2024) Pooja Singh; Monika Rajput; Manoj Pandey
Background: Head and neck cancer (HNC) is one of the most frequent malignancies in Asian males with a poor prognosis. Apart from well-known prognostic indicators, markers of tumor hypoxia can help us predict response to treatment and survival. Methods: A review of the literature on the present evidence and potential clinical importance of tumor hypoxia in head and neck cancer was carried out. The data obtained from the literature search is presented as a narrative review. Results: The literature shows possible associations between prognosis and low tumor oxygenation. Intermediate hypoxia biomarkers like HIF-1, GLUT-1, miRNA, and lactate, can help in predicting the response to therapy and survival as their altered expression is related to prognosis. Conclusions: Hypoxia is common in HNC and can be detected by use of biomarkers. The tumors that show expression of hypoxia biomarkers have poor prognosis except for patients with human papilloma virus-associated or VHL-associated cancers. Therapeutic targeting of hypoxia is emerging; however, it is still in its nascent stage, with increasing clinical trials hypoxia is set to emerge as an attractive therapeutic target in HNC. © 2024, The Author(s).
Unraveling the Neuroprotective Effect of Tinospora cordifolia in a Parkinsonian Mouse Model through the Proteomics Approach
(American Chemical Society, 2021) Hareram Birla; Chetan Keswani; Saumitra Sen Singh; Walia Zahra; Hagera Dilnashin; Aaina Singh Rathore; Richa Singh; Monika Rajput; Priyanka Keshri; Surya Pratap Singh
Stress-induced dopaminergic (DAergic) neuronal death in the midbrain region is the primary cause of Parkinson's disease (PD). Following the discovery of l-dopa, multiple drugs have been developed to improve the lifestyle of PD patients; however, none have been suitable for clinical use due to their multiple side effects. Tinospora cordifolia has been used in traditional medicines to treat neurodegenerative diseases. Previously, we reported the neuroprotective role of Tc via inhibition of NF-κB-associated proinflammatory cytokines against MPTP-intoxicated Parkinsonian mice. In the present study, we investigated the neuroprotective molecular mechanism of Tc in a rotenone (ROT)-intoxicated mouse model, using a proteomics approach. Mice were pretreated with Tc extract by oral administration, followed by ROT intoxication. Behavioral tests were performed to check motor functions of mice. Protein was isolated, and label-free quantification (LFQ) was carried out to identify differentially expressed protein (DEP) in control vs PD and PD vs treatment groups. Results were validated by qRT-PCR with the expression of target genes correlating with the proteomics data. In this study, we report 800 DEPs in control vs PD and 133 in PD vs treatment groups. In silico tools demonstrate significant enrichment of biochemical and molecular pathways with DEPs, which are known to be important for PD progression including mitochondrial gene expression, PD pathways, TGF-β signaling, and Alzheimer's disease. This study provides novel insights into the PD progression as well as new therapeutic targets. More importantly, it demonstrates that Tc can exert therapeutic effects by regulating multiple pathways, resulting in neuroprotection. © 2021 American Chemical Society.
Unravelling of the comparative Transcriptomic Profile of Gallbladder Cancer using mRNA sequencing
(Springer Science and Business Media B.V., 2022) Ruhi Dixit; Manoj Pandey; Monika Rajput; Vijay Kumar Shukla
Background: Gallbladder cancer (GBC) represents a wide geographical diversity as well as heterogeneity in clinical and genomic landscape. There seems to be little progress in the development of diagnostic biomarkers, targeted therapies or individualized approaches to GBC management. In this study, we investigated the whole transcriptome profile of GBC patients using RNA sequencing and identified key genes and pathways associated with gallbladder cancer using bioinformatics. Methodology: A total of 10 cases of GBC were collected and sequenced. The raw reads of the gallbladder sample was compared with the gallbladder normal control (SRA Database ID: ERX288537: HPA RNA-seq normal tissues gallbladder). Using Gene ontology analysis the differentially expressed genes were categorized into the biological pathway, cellular component, and molecular function. Pathway enrichment analyses, protein-protein interaction, transcription factor and miRNA interaction that regulate the expression of hub genes were conducted using bioinformatics tool. Results: A total of 954 differentially expressed mRNA transcripts were identified, including overexpression of REG4, TMEM238, S100A2, LYPD2, and KRT17, as well as underexpressed genes like CCKAR, IGSF10, CHRM2, CRISP3, and FGF19. Enrichment analysis showed the metabolic pathways to be the top five cancer pathways in gallbladder carcinogenesis besides PI3k-Akt signalling pathway, cAMP signalling pathway, miRNAs in cancer, and cell adhesion profile of GBC. Conclusions: CCKAR, CDKN2A and LRRK2 were found to be most involved genes in its progression and development through different regulatory pathways. Further, most of the genes were significantly involved in PI3k-Akt, Wnt and hedgehog signaling pathways which have a key role in gallbladder cancer development. © 2022, The Author(s), under exclusive licence to Springer Nature B.V.