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  1. Article ; Online: Mapinsights: deep exploration of quality issues and error profiles in high-throughput sequence data.

    Das, Subrata / Biswas, Nidhan K / Basu, Analabha

    Nucleic acids research

    2023  Volume 51, Issue 14, Page(s) e75

    Abstract: High-throughput sequencing (HTS) has revolutionized science by enabling super-fast detection of genomic variants at base-pair resolution. Consequently, it poses the challenging problem of identification of technical artifacts, i.e. hidden non-random ... ...

    Abstract High-throughput sequencing (HTS) has revolutionized science by enabling super-fast detection of genomic variants at base-pair resolution. Consequently, it poses the challenging problem of identification of technical artifacts, i.e. hidden non-random error patterns. Understanding the properties of sequencing artifacts holds the key in separating true variants from false positives. Here, we develop Mapinsights, a toolkit that performs quality control (QC) analysis of sequence alignment files, capable of detecting outliers based on sequencing artifacts of HTS data at a deeper resolution compared with existing methods. Mapinsights performs a cluster analysis based on novel and existing QC features derived from the sequence alignment for outlier detection. We applied Mapinsights on community standard open-source datasets and identified various quality issues including technical errors related to sequencing cycles, sequencing chemistry, sequencing libraries and across various orthogonal sequencing platforms. Mapinsights also enables identification of anomalies related to sequencing depth. A logistic regression-based model built on the features of Mapinsights shows high accuracy in detecting 'low-confidence' variant sites. Quantitative estimates and probabilistic arguments provided by Mapinsights can be utilized in identifying errors, bias and outlier samples, and also aid in improving the authenticity of variant calls.
    MeSH term(s) High-Throughput Nucleotide Sequencing/methods ; Sequence Analysis, DNA/methods ; Software
    Language English
    Publishing date 2023-08-14
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 186809-3
    ISSN 1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
    ISSN (online) 1362-4962 ; 1362-4954
    ISSN 0301-5610 ; 0305-1048
    DOI 10.1093/nar/gkad539
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Analysis of RNA sequences of 3636 SARS-CoV-2 collected from 55 countries reveals selective sweep of one virus type.

    Biswas, Nidhan K / Majumder, Partha P

    The Indian journal of medical research

    2020  Volume 151, Issue 5, Page(s) 450–458

    Abstract: Background & objectives: SARS-CoV-2 (Severe acute respiratory syndrome coronavirus-2) is evolving with the progression of the pandemic. This study was aimed to investigate the diversity and evolution of the coronavirus SARS-CoV-2 with progression of the ...

    Abstract Background & objectives: SARS-CoV-2 (Severe acute respiratory syndrome coronavirus-2) is evolving with the progression of the pandemic. This study was aimed to investigate the diversity and evolution of the coronavirus SARS-CoV-2 with progression of the pandemic over time and to identify similarities and differences of viral diversity and evolution across geographical regions (countries).
    Methods: Publicly available data on type definitions based on whole-genome sequences of the SARS-CoV-2 sampled during December and March 2020 from 3636 infected patients spread over 55 countries were collected. Phylodynamic analyses were performed and the temporal and spatial evolution of the virus was examined.
    Results: It was found that (i) temporal variation in frequencies of types of the coronavirus was significant; ancestral viruses of type O were replaced by evolved viruses belonging to type A2a; (ii) spatial variation was not significant; with the spread of SARS-CoV-2, the dominant virus was the A2a type virus in every geographical region; (iii) within a geographical region, there was significant micro-level variation in the frequencies of the different viral types, and (iv) the evolved coronavirus of type A2a swept rapidly across all continents.
    Interpretation & conclusions: SARS-CoV-2 belonging to the A2a type possesses a non-synomymous variant (D614G) that possibly eases the entry of the virus into the lung cells of the host. This may be the reason why the A2a type has an advantage to infect and survive and as a result has rapidly swept all geographical regions. Therefore, large-scale sequencing of coronavirus genomes and, as required, of host genomes should be undertaken in India to identify regional and ethnic variation in viral composition and its interaction with host genomes. Further, careful collection of clinical and immunological data of the host can provide deep learning in relation to infection and transmission of the types of coronavirus genomes.
    MeSH term(s) Betacoronavirus/genetics ; Betacoronavirus/pathogenicity ; COVID-19 ; Coronavirus Infections/epidemiology ; Coronavirus Infections/virology ; Evolution, Molecular ; Humans ; India/epidemiology ; Internationality ; Molecular Typing ; Pandemics ; Phylogeography ; Pneumonia, Viral/epidemiology ; Pneumonia, Viral/virology ; RNA, Viral/analysis ; RNA, Viral/genetics ; SARS-CoV-2 ; Spatio-Temporal Analysis
    Chemical Substances RNA, Viral
    Keywords covid19
    Language English
    Publishing date 2020-07-06
    Publishing country India
    Document type Journal Article
    ZDB-ID 390883-5
    ISSN 0971-5916 ; 0019-5340
    ISSN 0971-5916 ; 0019-5340
    DOI 10.4103/ijmr.IJMR_1125_20
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: MAL expression downregulation through suppressive H3K27me3 marks at the promoter in HPV16-related cervical cancers is prognostically relevant and manifested by the interplay of novel MAL antisense long noncoding RNA AC103563.8, E7 oncoprotein and EZH2.

    Sinha, Abarna / Ghosh, Abhisikta / Ghosh, Arnab / Mathai, Sonia / Bhaumik, Jaydip / Mukhopadhyay, Asima / Maitra, Arindam / Biswas, Nidhan K / Sengupta, Sharmila

    Clinical epigenetics

    2024  Volume 16, Issue 1, Page(s) 40

    Abstract: Background: MAL (T-lymphocyte maturation-associated protein) is highly downregulated in most cancers, including cervical cancer (CaCx), attributable to promoter hypermethylation. Long noncoding RNA genes (lncGs) play pivotal roles in CaCx pathogenesis, ... ...

    Abstract Background: MAL (T-lymphocyte maturation-associated protein) is highly downregulated in most cancers, including cervical cancer (CaCx), attributable to promoter hypermethylation. Long noncoding RNA genes (lncGs) play pivotal roles in CaCx pathogenesis, by interacting with human papillomavirus (HPV)-encoded oncoproteins, and epigenetically regulating coding gene expression. Hence, we attempted to decipher the impact and underlying mechanisms of MAL downregulation in HPV16-related CaCx pathogenesis, by interrogating the interactive roles of MAL antisense lncRNA AC103563.8, E7 oncoprotein and PRC2 complex protein, EZH2.
    Results: Employing strand-specific RNA-sequencing, we confirmed the downregulated expression of MAL in association with poor overall survival of CaCx patients bearing HPV16, along with its antisense long noncoding RNA (lncRNA) AC103563.8. The strength of positive correlation between MAL and AC103563.8 was significantly high among patients compared to normal individuals. While downregulated expression of MAL was significantly associated with poor overall survival of CaCx patients bearing HPV16, AC103563.8 did not reveal any such association. We confirmed the enrichment of chromatin suppressive mark, H3K27me3 at MAL promoter, using ChIP-qPCR in HPV16-positive SiHa cells. Subsequent E7 knockdown in such cells significantly increased MAL expression, concomitant with decreased EZH2 expression and H3K27me3 marks at MAL promoter. In silico analysis revealed that both E7 and EZH2 bear the potential of interacting with AC103563.8, at the same binding domain. RNA immunoprecipitation with anti-EZH2 and anti-E7 antibodies, respectively, and subsequent quantitative PCR analysis in E7-silenced and unperturbed SiHa cells confirmed the interaction of AC103563.8 with EZH2 and E7, respectively. Apparently, AC103563.8 seems to preclude EZH2 and bind with E7, failing to block EZH2 function in patients. Thereby, enhanced EZH2 expression in the presence of E7 could potentially inactivate the MAL promoter through H3K27me3 marks, corroborating our previous results of MAL expression downregulation in patients.
    Conclusion: AC103563.8-E7-EZH2 axis, therefore, appears to crucially regulate the expression of MAL, through chromatin inactivation in HPV16-CaCx pathogenesis, warranting therapeutic strategy development.
    MeSH term(s) Female ; Humans ; Chromatin/metabolism ; DNA Methylation ; Down-Regulation ; Enhancer of Zeste Homolog 2 Protein/genetics ; Enhancer of Zeste Homolog 2 Protein/metabolism ; Histones/metabolism ; Human papillomavirus 16/genetics ; Oncogene Proteins, Viral/genetics ; Oncogene Proteins, Viral/metabolism ; Papillomavirus E7 Proteins/genetics ; Papillomavirus E7 Proteins/metabolism ; RNA, Long Noncoding/genetics ; RNA, Long Noncoding/metabolism ; Uterine Cervical Neoplasms/pathology ; Myelin and Lymphocyte-Associated Proteolipid Proteins/genetics ; Myelin and Lymphocyte-Associated Proteolipid Proteins/metabolism
    Chemical Substances Chromatin ; Enhancer of Zeste Homolog 2 Protein (EC 2.1.1.43) ; EZH2 protein, human (EC 2.1.1.43) ; Histones ; Oncogene Proteins, Viral ; Papillomavirus E7 Proteins ; RNA, Long Noncoding ; MAL protein, human ; Myelin and Lymphocyte-Associated Proteolipid Proteins
    Language English
    Publishing date 2024-03-10
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553921-8
    ISSN 1868-7083 ; 1868-7075
    ISSN (online) 1868-7083
    ISSN 1868-7075
    DOI 10.1186/s13148-024-01651-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Analysis of RNA sequences of 3636 SARS-CoV-2 collected from 55 countries reveals selective sweep of one virus type

    Biswas, Nidhan K / Majumder, Partha P

    Indian journal of medical research

    Abstract: Background & objectives: SARS-CoV-2 (Severe acute respiratory syndrome coronavirus-2) is evolving with the progression of the pandemic. This study was aimed to investigate the diversity and evolution of the coronavirus SARS-CoV-2 with progression of the ... ...

    Abstract Background & objectives: SARS-CoV-2 (Severe acute respiratory syndrome coronavirus-2) is evolving with the progression of the pandemic. This study was aimed to investigate the diversity and evolution of the coronavirus SARS-CoV-2 with progression of the pandemic over time and to identify similarities and differences of viral diversity and evolution across geographical regions (countries). Methods: Publicly available data on type definitions based on whole-genome sequences of the SARS-CoV-2 sampled during December and March 2020 from 3636 infected patients spread over 55 countries were collected. Phylodynamic analyses were performed and the temporal and spatial evolution of the virus was examined. Results: It was found that (i) temporal variation in frequencies of types of the coronavirus was significant; ancestral viruses of type O were replaced by evolved viruses belonging to type A2a; (ii) spatial variation was not significant; with the spread of SARS-CoV-2, the dominant virus was the A2a type virus in every geographical region; (iii) within a geographical region, there was significant micro-level variation in the frequencies of the different viral types, and (iv) the evolved coronavirus of type A2a swept rapidly across all continents. Interpretation & conclusions: SARS-CoV-2 belonging to the A2a type possesses a non-synomymous variant (D614G) that possibly eases the entry of the virus into the lung cells of the host. This may be the reason why the A2a type has an advantage to infect and survive and as a result has rapidly swept all geographical regions. Therefore, large-scale sequencing of coronavirus genomes and, as required, of host genomes should be undertaken in India to identify regional and ethnic variation in viral composition and its interaction with host genomes. Further, careful collection of clinical and immunological data of the host can provide deep learning in relation to infection and transmission of the types of coronavirus genomes.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #32474553
    Database COVID19

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  5. Article ; Online: Analysis of RNA sequences of 3636 SARS-CoV-2 collected from 55 countries reveals selective sweep of one virus type

    Majumder, ParthaP / Biswas, NidhanK

    Indian Journal of Medical Research

    2020  Volume 151, Issue 5, Page(s) 450

    Keywords General Biochemistry, Genetics and Molecular Biology ; General Medicine ; covid19
    Language English
    Publisher Medknow
    Publishing country in
    Document type Article ; Online
    ZDB-ID 390883-5
    ISSN 0019-5340 ; 0971-5916
    ISSN 0019-5340 ; 0971-5916
    DOI 10.4103/ijmr.ijmr_1125_20
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Unfurling the functional association between long intergenic noncoding RNAs (lincRNAs) and HPV16-related cervical cancer pathogenesis through weighted gene co-expression network analysis of differentially expressed lincRNAs and coding genes.

    Sinha, Abarna / Ghosh, Sahana / Ghosh, Abhisikta / Ghosh, Arnab / Mathai, Sonia / Bhaumik, Jaydip / Mukhopadhyay, Asima / Maitra, Arindam / Biswas, Nidhan K / Sengupta, Sharmila

    Carcinogenesis

    2024  

    Abstract: Long intergenic noncoding RNAs (lincRNAs) do not overlap annotated coding genes and are located in intergenic regions, as opposed to antisense and sense-intronic lncRNAs, located in genic regions. LincRNAs influence gene expression profiles and are ... ...

    Abstract Long intergenic noncoding RNAs (lincRNAs) do not overlap annotated coding genes and are located in intergenic regions, as opposed to antisense and sense-intronic lncRNAs, located in genic regions. LincRNAs influence gene expression profiles and are thereby key to disease pathogenesis. In this study, we assessed the association between lincRNAs and HPV16-positive cervical cancer (CaCx) pathogenesis using weighted gene co-expression network analysis (WGCNA) with coding genes, comparing differentially expressed lincRNA and coding genes (DElincGs and DEcGs, respectively) in HPV16-positive patients with CaCx (n = 44) with those in HPV-negative healthy individuals (n = 34). Our analysis revealed five DElincG modules, co-expressing and correlating with DEcGs. We validated a substantial number of such module-specific correlations in the HPV16-positive cancer TCGA-CESC dataset. Four such modules, displayed significant correlations with patient traits, such as HPV16 physical status, lymph node involvement, and overall survival (OS), highlighting a collaborative effect of all genes within specific modules on traits. Using the DAVID bioinformatics knowledgebase, we identified the underlying biological processes associated with these modules as cancer development and progression-associated pathways. Next, we identified the top 10 DElincGs with the highest connectivity within each functional module. Focusing on the prognostic module hub genes, downregulated CTD-2619J13.13 expression was associated with poor patient OS. This lincRNA gene interacted with 25 coding genes of its module and was associated with such biological processes as keratinization loss and keratinocyte differentiation, reflecting severe disease phenotypes. This study has translational relevance in fighting various cancers with high mortality rates in underdeveloped countries.
    Language English
    Publishing date 2024-03-06
    Publishing country England
    Document type Journal Article
    ZDB-ID 603134-1
    ISSN 1460-2180 ; 0143-3334
    ISSN (online) 1460-2180
    ISSN 0143-3334
    DOI 10.1093/carcin/bgae019
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Computational prediction of the molecular mechanism of statin group of drugs against SARS-CoV-2 pathogenesis.

    Ghosh, Dipanjan / Ghosh Dastidar, Debabrata / Roy, Kamalesh / Ghosh, Arnab / Mukhopadhyay, Debanjan / Sikdar, Nilabja / Biswas, Nidhan K / Chakrabarti, Gopal / Das, Amlan

    Scientific reports

    2022  Volume 12, Issue 1, Page(s) 6241

    Abstract: Recently published clinical data from COVID-19 patients indicated that statin therapy is associated with a better clinical outcome and a significant reduction in the risk of mortality. In this study by computational analysis, we have aimed to predict the ...

    Abstract Recently published clinical data from COVID-19 patients indicated that statin therapy is associated with a better clinical outcome and a significant reduction in the risk of mortality. In this study by computational analysis, we have aimed to predict the possible mechanism of the statin group of drugs by which they can inhibit SARS-CoV-2 pathogenesis. Blind docking of the critical structural and functional proteins of SARS-CoV-2 like RNA-dependent RNA polymerase, M-protease of 3-CL-Pro, Helicase, and the Spike proteins ( wild type and mutants from different VOCs) were performed using the Schrodinger docking tool. We observed that fluvastatin and pitavastatin showed fair, binding affinities to RNA polymerase and 3-CL-Pro, whereas fluvastatin showed the strongest binding affinity to the helicase. Fluvastatin also showed the highest affinity for the Spike
    MeSH term(s) Antiviral Agents/therapeutic use ; COVID-19/drug therapy ; Fluvastatin/pharmacology ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology ; Molecular Docking Simulation ; Molecular Dynamics Simulation ; SARS-CoV-2
    Chemical Substances Antiviral Agents ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Fluvastatin (4L066368AS)
    Language English
    Publishing date 2022-04-14
    Publishing country England
    Document type Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-022-09845-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Integrative analysis of genomic and transcriptomic data of normal, tumour, and co-occurring leukoplakia tissue triads drawn from patients with gingivobuccal oral cancer identifies signatures of tumour initiation and progression.

    Ghosh, Arnab / Das, Chitrarpita / Ghose, Sandip / Maitra, Arindam / Roy, Bidyut / Majumder, Partha P / Biswas, Nidhan K

    The Journal of pathology

    2022  Volume 257, Issue 5, Page(s) 593–606

    Abstract: A thickened, white patch - leukoplakia - in the oral cavity is usually benign, but sometimes (in ~9% of individuals) it progresses to malignant tumour. Because the genomic basis of this progression is poorly understood, we undertook this study and ... ...

    Abstract A thickened, white patch - leukoplakia - in the oral cavity is usually benign, but sometimes (in ~9% of individuals) it progresses to malignant tumour. Because the genomic basis of this progression is poorly understood, we undertook this study and collected samples of four tissues - leukoplakia, tumour, adjacent normal, and blood - from each of 28 patients suffering from gingivobuccal oral cancer. We performed multiomics analysis of the 112 collected tissues (four tissues per patient from 28 patients) and integrated information on progressive changes in the mutational and transcriptional profiles of each patient to create this genomic narrative. Additionally, we generated and analysed whole-exome sequence data from leukoplakia tissues collected from 11 individuals not suffering from oral cancer. Nonsynonymous somatic mutations in the CASP8 gene were identified as the likely events to initiate malignant transformation, since these were frequently shared between tumour and co-occurring leukoplakia. CASP8 alterations were also shown to enhance expressions of genes that favour lateral spread of mutant cells. During malignant transformation, additional pathogenic mutations are acquired in key genes (TP53, NOTCH1, HRAS) (41% of patients); chromosomal-instability (arm-level deletions of 19p and q, focal-deletion of DNA-repair pathway genes and NOTCH1, amplification of EGFR) (77%), and increased APOBEC-activity (23%) are also observed. These additional alterations were present singly (18% of patients) or in combination (68%). Some of these alterations likely impact immune-dynamics of the evolving transformed tissue; progression to malignancy is associated with immune suppression through infiltration of regulatory T-cells (56%), depletion of cytotoxic T-cells (68%), and antigen-presenting dendritic cells (72%), with a concomitant increase in inflammation (92%). Patients can be grouped into three clusters by the estimated time to development of cancer from precancer by acquiring additional mutations (range: 4-10 years). Our findings provide deep molecular insights into the evolutionary processes and trajectories of oral cancer initiation and progression. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
    MeSH term(s) Cell Transformation, Neoplastic/genetics ; Exome ; Genomics ; Humans ; Leukoplakia/genetics ; Mouth Neoplasms/genetics ; Mouth Neoplasms/pathology ; Mutation ; Transcriptome
    Language English
    Publishing date 2022-04-21
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3119-7
    ISSN 1096-9896 ; 0022-3417
    ISSN (online) 1096-9896
    ISSN 0022-3417
    DOI 10.1002/path.5900
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Upper respiratory tract microbiome profiles in SARS-CoV-2 Delta and Omicron infected patients exhibit variant specific patterns and robust prediction of disease groups.

    Nath, Shankha / Sarkar, Mousumi / Maddheshiya, Ankita / De, Debjit / Paul, Shouvik / Dey, Souradeep / Pal, Kuhu / Roy, Suman Kr / Ghosh, Ayan / Sengupta, Sharmila / Paine, Suman Kalyan / Biswas, Nidhan K / Basu, Analabha / Mukherjee, Souvik

    Microbiology spectrum

    2023  Volume 11, Issue 6, Page(s) e0236823

    Abstract: Importance: The role of the upper respiratory tract (URT) microbiome in predicting lung health has been documented in several studies. The dysbiosis in COVID patients has been associated with disease outcomes by modulating the host immune system. ... ...

    Abstract Importance: The role of the upper respiratory tract (URT) microbiome in predicting lung health has been documented in several studies. The dysbiosis in COVID patients has been associated with disease outcomes by modulating the host immune system. However, although it has been known that different SARS-CoV-2 variants manifest distinct transmissibility and mortality rates in human populations, their effect on the composition and diversity of the URT microbiome has not been studied to date. Unlike the older variant (Delta), the newer variant (Omicron) have become more transmissible with lesser mortality and the symptoms have also changed significantly. Hence, in the present study, we have investigated the change in the URT microbiome associated with Delta and Omicron variants and identified variant-specific signatures that will be useful in the assessment of lung health and can be utilized for nasal probiotic therapy in the future.
    MeSH term(s) Humans ; SARS-CoV-2/genetics ; COVID-19 ; Microbiota/genetics ; Nose
    Language English
    Publishing date 2023-10-31
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2807133-5
    ISSN 2165-0497 ; 2165-0497
    ISSN (online) 2165-0497
    ISSN 2165-0497
    DOI 10.1128/spectrum.02368-23
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Identification of HPV16 positive cervical cancer subsets characterized by divergent immune and oncogenic phenotypes with potential implications for immunotherapy.

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

    Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine

    2023  Volume 45, Issue 1, Page(s) 55–69

    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 ... ...

    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.
    MeSH term(s) Female ; Humans ; Uterine Cervical Neoplasms/genetics ; Uterine Cervical Neoplasms/therapy ; Human papillomavirus 16/genetics ; Immunotherapy ; Phenotype ; CD8-Positive T-Lymphocytes
    Language English
    Publishing date 2023-08-21
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 605825-5
    ISSN 1423-0380 ; 0289-5447 ; 1010-4283
    ISSN (online) 1423-0380
    ISSN 0289-5447 ; 1010-4283
    DOI 10.3233/TUB-220035
    Database MEDical Literature Analysis and Retrieval System OnLINE

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