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pmid:35433487

Identification of LncRNA Prognostic Signature Associated With Genomic Instability in Pancreatic Adenocarcinoma.

Jinfeng Zhu · Qian Huang · Xingyu Peng · Chen Luo · Sicheng Liu · Zitao Liu · Xun Wu · Hongliang Luo

Frontiers in oncology · 2022 doi:10.3389/fonc.2022.799475

Paper

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Experiment

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Data

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title
Identification of LncRNA Prognostic Signature Associated With Genomic Instability in Pancreatic Adenocarcinoma.
doi
10.3389/fonc.2022.799475
pmid
35433487
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[0]
Jinfeng Zhu
[1]
Qian Huang
[2]
Xingyu Peng
[3]
Chen Luo
[4]
Sicheng Liu
[5]
Zitao Liu
[6]
Xun Wu
[7]
Hongliang Luo
journal
Frontiers in oncology
year
2022
abstract
Background: Genomic instability (GI) is a critical feature of cancer which plays a key role in the occurrence and development of pancreatic adenocarcinoma (PAAD). Long non-coding RNA (LncRNA) is an emerging prognostic biomarker because it is involved in regulating GI. Recently, researchers used such GI-related LncRNAs (GILncRNAs) to establish a prognostic signature for patients with cancer and helped in predicting the overall prognosis of the patients. However, it is evident that patients with PAAD still lack such prognostic signature constructed with GILncRNA. Methods: The present study screened GILncRNAs from 83 patients with PAAD. Prognosis-related GILncRNAs were identified by univariate Cox regression analysis. The correlation coefficients of these GILncRNAs were obtained by multivariate Cox regression analysis and used to construct a signature. The signature in the present study was then assessed through survival analysis, mutation correlation analysis, independent prognostic analysis, and clinical stratification analysis in the training set and validated in the testing as well as all TCGA set. The current study performed external clinical relevance validation of the signature and validated the effect of AC108134.2 in GILncSig on PAAD using in vitro experiments. Finally, the function of GILncRNA signature (GILncSig) dependent on Gene Ontology enrichment analysis was explored and chemotherapeutic drug sensitivity analysis was also performed. Results: Results of the present study found that a total of 409 GILncRNAs were identified, 5 of which constituted the prognostic risk signature in this study, namely, AC095057.3, AC108134.2, AC124798.1, AL606834.1, and AC104695.4. It was found that the signature of the present study was better than others in predicting the overall survival and applied to patients with PAAD of all ages, genders, and tumor grades. Further, it was noted that the signature of the current study in the GSE102238, was correlated with tumor length, and tumor stage of patients with PAAD. In vitro, functional experiments were used in the present study to validate that AC108134.2 is associated with PAAD genomic instability and progression. Notably, results of the pRRophetic analysis in the current study showed that the high-risk group possessed reverse characteristics and was sensitive to chemotherapy. Conclusions: In conclusion, it was evident that the GILncSig used in the present study has good prognostic performance. Therefore, the signature may become a potential sensitive biological indicator of PAAD chemotherapy, which may help in clinical decision-making and management of patients with cancer.
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The “survival” package was used to conduct univariate and multivariate Cox regression analysis on the survival data of GILncRNAs in the training set to complete the construction of the prognostic risk signature.
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sections[6] "Establishment of Prognostic Risk Signature" paragraph 2
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The “survival” package was used to conduct univariate and multivariate Cox regression analysis on the survival data of GILncRNAs in the training set to complete the construction of the prognostic risk signature.
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Publicly available datasets were analyzed in this study. This data can be found in the TCGA database here: https://portal.gdc.cancer.gov/, and the GSE102238: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE102238.
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Publicly available datasets were analyzed in this study. This data can be found in the TCGA database here: https://portal.gdc.cancer.gov/, and the GSE102238: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE102238.
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A five-lncRNA genomic-instability-related prognostic signature was established for pancreatic adenocarcinoma and achieved a 5-year survival-prediction AUC of 0.953 in the TCGA set.
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sections[26] "Signature Comparison and External Verification" paragraph 2
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By plotting the ROC curve, it was found that the area under the ROC curve of the current signature for 1-, 3-, and 5-year survival prediction was all the largest (AUC = 0.752, 0.798, and 0.953, respectively), which was significantly greater than those established by Lei (AUC = 0.646, 0.713, and 0.735) and Wang (AUC = 0.719, 0.671, and 0.726) ( Figures 7A–C ).
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A five-lncRNA genomic-instability-related prognostic signature was established for pancreatic adenocarcinoma and achieved a 5-year survival-prediction AUC of 0.953 in the TCGA set.
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he Declaration of Helsinki. Cell Culture and Transfection The human PAAD cell line (BxPC-3 cell) was p
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ine 3000 reagents (Invitrogen, Waltham, USA) transfected BxPC-3 according to standard guidelines. The
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role of AC108134.2 in PAAD cells, siRNA was transfected into BxPC-3 cells and it was evident that th
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e identification of the cell bank. They were cultured in 1640 (Gibco, USA) supplemented with 10% feta
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PC-3 cells was verified through qRT-PCR. (C) CCK-8 assay was used to detect the changes in cell
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< 0.001. ns stands for p > 0.05. Results of CCK-8 showed that knockdown of AC108134.2 suppress
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PC-3 cells after silencing of AC108134.2 (G) Western blot analysis of the expression of genomic instab
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34.2 affects genomic instability. Results of western blotting showed that after the knockdown of AC108134.
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{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35433487", "kind": "science-record", "revision": 4, "content_hash": "sha256:279f519c9658b2f582bcc7fc41ac2d4f26f8875100f2c022818d354f0e187c3f", "created_at": "2026-11-01T18:14:16Z", "updated_at": "2026-11-01T22:06:19Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of LncRNA Prognostic Signature Associated With Genomic Instability in Pancreatic Adenocarcinoma.", "doi": "10.3389/fonc.2022.799475", "pmid": "35433487", "authors": ["Jinfeng Zhu", "Qian Huang", "Xingyu Peng", "Chen Luo", "Sicheng Liu", "Zitao Liu", "Xun Wu", "Hongliang Luo"], "journal": "Frontiers in oncology", "year": 2022, "abstract": "Background: Genomic instability (GI) is a critical feature of cancer which plays a key role in the occurrence and development of pancreatic adenocarcinoma (PAAD). Long non-coding RNA (LncRNA) is an emerging prognostic biomarker because it is involved in regulating GI. Recently, researchers used such GI-related LncRNAs (GILncRNAs) to establish a prognostic signature for patients with cancer and helped in predicting the overall prognosis of the patients. However, it is evident that patients with PAAD still lack such prognostic signature constructed with GILncRNA.\nMethods: The present study screened GILncRNAs from 83 patients with PAAD. Prognosis-related GILncRNAs were identified by univariate Cox regression analysis. The correlation coefficients of these GILncRNAs were obtained by multivariate Cox regression analysis and used to construct a signature. The signature in the present study was then assessed through survival analysis, mutation correlation analysis, independent prognostic analysis, and clinical stratification analysis in the training set and validated in the testing as well as all TCGA set. The current study performed external clinical relevance validation of the signature and validated the effect of AC108134.2 in GILncSig on PAAD using in vitro experiments. Finally, the function of GILncRNA signature (GILncSig) dependent on Gene Ontology enrichment analysis was explored and chemotherapeutic drug sensitivity analysis was also performed.\nResults: Results of the present study found that a total of 409 GILncRNAs were identified, 5 of which constituted the prognostic risk signature in this study, namely, AC095057.3, AC108134.2, AC124798.1, AL606834.1, and AC104695.4. It was found that the signature of the present study was better than others in predicting the overall survival and applied to patients with PAAD of all ages, genders, and tumor grades. Further, it was noted that the signature of the current study in the GSE102238, was correlated with tumor length, and tumor stage of patients with PAAD. In vitro, functional experiments were used in the present study to validate that AC108134.2 is associated with PAAD genomic instability and progression. Notably, results of the pRRophetic analysis in the current study showed that the high-risk group possessed reverse characteristics and was sensitive to chemotherapy.\nConclusions: In conclusion, it was evident that the GILncSig used in the present study has good prognostic performance. Therefore, the signature may become a potential sensitive biological indicator of PAAD chemotherapy, which may help in clinical decision-making and management of patients with cancer.", "claims": [{"id": "claim-method", "statement": "The “survival” package was used to conduct univariate and multivariate Cox regression analysis on the survival data of GILncRNAs in the training set to complete the construction of the prognostic risk signature.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35433487", "locator": "sections[6] \"Establishment of Prognostic Risk Signature\" paragraph 2", "quote": "The “survival” package was used to conduct univariate and multivariate Cox regression analysis on the survival data of GILncRNAs in the training set to complete the construction of the prognostic risk signature."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. This data can be found in the TCGA database here: https://portal.gdc.cancer.gov/, and the GSE102238: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE102238.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35433487", "locator": "sections[32] \"Data Availability Statement\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study. This data can be found in the TCGA database here: https://portal.gdc.cancer.gov/, and the GSE102238: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE102238."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A five-lncRNA genomic-instability-related prognostic signature was established for pancreatic adenocarcinoma and achieved a 5-year survival-prediction AUC of 0.953 in the TCGA set.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35433487", "locator": "sections[26] \"Signature Comparison and External Verification\" paragraph 2", "quote": "By plotting the ROC curve, it was found that the area under the ROC curve of the current signature for 1-, 3-, and 5-year survival prediction was all the largest (AUC = 0.752, 0.798, and 0.953, respectively), which was significantly greater than those established by Lei (AUC = 0.646, 0.713, and 0.735) and Wang (AUC = 0.719, 0.671, and 0.726) ( Figures 7A–C )."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A five-lncRNA genomic-instability-related prognostic signature was established for pancreatic adenocarcinoma and achieved a 5-year survival-prediction AUC of 0.953 in the TCGA set.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:35433487"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE102238"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE102238"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35433487", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fonc.2022.799475", "sha256": "sha256:8541fe459232627dde3a6244be979c52c3505d7edd771eeadca579b80018e9c0", "bytes": 46965, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fonc.2022.799475", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9012103", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE102238", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE102238", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE102238", "version": null, "note": "Publicly available datasets were analyzed in this study. 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Cell Culture and Transfection The human PAAD cell line (BxPC-3 cell) was p", "chased from GenePharma (Shanghai, China) and transfected with Lipofectamine 3000 reagents (Invitrogen", "ine 3000 reagents (Invitrogen, Waltham, USA) transfected BxPC-3 according to standard guidelines. The", "role of AC108134.2 in PAAD cells, siRNA was transfected into BxPC-3 cells and it was evident that th"], "order_basis": "paper_text_order:3909", "id": "assay:1"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["e identification of the cell bank. They were cultured in 1640 (Gibco, USA) supplemented with 10% feta"], "order_basis": "paper_text_order:4157", "id": "assay:2"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["PC-3 cells was verified through qRT-PCR. (C) CCK-8 assay was used to detect the changes in cell", "< 0.001. ns stands for p > 0.05. Results of CCK-8 showed that knockdown of AC108134.2 suppress"], "order_basis": "paper_text_order:6084", "id": "assay:3"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["PC-3 cells after silencing of AC108134.2 (G) Western blot analysis of the expression of genomic instab", "34.2 affects genomic instability. Results of western blotting showed that after the knockdown of AC108134."], "order_basis": "paper_text_order:6554", "id": "assay:4"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["cox_ph"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The “survival” package was used to conduct univariate and multivariate Cox regression analysis on the survival data of GILncRNAs in the training set to complete the construction of the prognostic risk signature."], "order_basis": "consumes_earlier_output", "id": "assay:5"}]}