A Qualitative Transcriptional Signature for the Histological Reclassification of Lung Squamous Cell carcinomas and Adenocarcinomas

Abstract Background: Targeted therapy for non-small cell lung cancer is histology dependent. However, histological classification by routine pathological assessment with hematoxylin-eosin staining and immunostaining for poorly differentiated tumors, particularly those from small biopsies, is still challenging. Additionally, the effectiveness of immunomarkers is limited by technical inconsistencies of immunostaining and lack of standardization for staining interpretation. Results: Using gene expression profiles of pathologically-determined lung adenocarcinomas and squamous cell carcinomas, denoted as pADC and pSCC respectively, we developed a qualitative transcriptional signature, based on the within-sample relative gene expression orderings (REOs) of gene pairs, to distinguish ADC from SCC. The signature consists of two genes, KRT5 and AGR2, which has the stable REO pattern of KRT5 > AGR2 in pSCC and KRT5 < AGR2 in pADC. In the two test datasets with relative unambiguous NSCLC types, the apparent accuracy of the signature were 94.44% and 98.41%, respectively. In the other integrated dataset for frozen tissues, the signature reclassified 4.22% of the 805 pADC patients as SCC and 12% of the 125 pSCC patients as ADC. Similar results were observed in the clinical challenging cases, including FFPE specimens, mixed tumors, small biopsy specimens and poorly differentiated specimens. The survival analyses showed that the pADC patients reclassified as SCC had significantly shorter overall survival than the signature-confirmed pADC patients (log-rank p = 0.0123, HR = 1.89), consisting with the knowledge that SCC patients suffer poor prognoses than ADC patients. The proliferative activity, subtype-specific marker genes and consensus clustering analyses also supported the correctness of our signature. Conclusions: The non-subjective qualitative REOs signature could effectively distinguish ADC from SCC, which would be an auxiliary test for the pathological assessment of the ambiguous cases.

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A qualitative transcriptional signature for the histological reclassification of lung squamous cell carcinomas and adenocarcinomas

BMC Genomics ◽

10.1186/s12864-019-6086-2 ◽

2019 ◽

Vol 20 (1) ◽

Author(s):

Xin Li ◽

Gengen Shi ◽

Qingsong Chu ◽

Wenbin Jiang ◽

Yixin Liu ◽

...

Keyword(s):

Gene Expression ◽

Squamous Cell ◽

Expression Profiles ◽

Squamous Cell Carcinomas ◽

Marker Genes ◽

Specific Marker ◽

Consensus Clustering ◽

Transcriptional Signature ◽

Poorly Differentiated ◽

Pathological Assessment

Abstract Background Targeted therapy for non-small cell lung cancer is histology dependent. However, histological classification by routine pathological assessment with hematoxylin-eosin staining and immunostaining for poorly differentiated tumors, particularly those from small biopsies, is still challenging. Additionally, the effectiveness of immunomarkers is limited by technical inconsistencies of immunostaining and lack of standardization for staining interpretation. Results Using gene expression profiles of pathologically-determined lung adenocarcinomas and squamous cell carcinomas, denoted as pADC and pSCC respectively, we developed a qualitative transcriptional signature, based on the within-sample relative gene expression orderings (REOs) of gene pairs, to distinguish ADC from SCC. The signature consists of two genes, KRT5 and AGR2, which has the stable REO pattern of KRT5 > AGR2 in pSCC and KRT5 < AGR2 in pADC. In the two test datasets with relative unambiguous NSCLC types, the apparent accuracy of the signature were 94.44 and 98.41%, respectively. In the other integrated dataset for frozen tissues, the signature reclassified 4.22% of the 805 pADC patients as SCC and 12% of the 125 pSCC patients as ADC. Similar results were observed in the clinical challenging cases, including FFPE specimens, mixed tumors, small biopsy specimens and poorly differentiated specimens. The survival analyses showed that the pADC patients reclassified as SCC had significantly shorter overall survival than the signature-confirmed pADC patients (log-rank p = 0.0123, HR = 1.89), consisting with the knowledge that SCC patients suffer poor prognoses than ADC patients. The proliferative activity, subtype-specific marker genes and consensus clustering analyses also supported the correctness of our signature. Conclusions The non-subjective qualitative REOs signature could effectively distinguish ADC from SCC, which would be an auxiliary test for the pathological assessment of the ambiguous cases.

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A Qualitative Transcriptional Signature for the Histological Reclassification of Lung Squamous Cell carcinomas and Adenocarcinomas

10.21203/rs.2.9782/v1 ◽

2019 ◽

Author(s):

Xin Li ◽

Gengen Shi ◽

Qingsong Chu ◽

Wenbin Jiang ◽

Yixin Liu ◽

...

Keyword(s):

Gene Expression ◽

Squamous Cell ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Squamous Cell Carcinomas ◽

Transcriptional Signature ◽

Poorly Differentiated ◽

Histological Reclassification ◽

Hematoxylin Eosin ◽

Relative Gene

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Comparison of Gene Expression Profiles of Pretreatment and Recurrent Locally-Advanced Head and Neck Squamous Cell Carcinomas Treated With Chemoradiation

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2013.06.1764 ◽

2013 ◽

Vol 87 (2) ◽

pp. S666

Author(s):

A.M. Baschnagel ◽

B.J. Thibodeau ◽

L. Williams ◽

L. Fortier ◽

B. Ketelsen ◽

...

Keyword(s):

Gene Expression ◽

Head And Neck ◽

Squamous Cell ◽

Expression Profiles ◽

Locally Advanced ◽

Gene Expression Profiles ◽

Squamous Cell Carcinomas ◽

Advanced Head

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A Resource for the Transcriptional Signature of Bona Fide Trophoblast Stem Cells and Analysis of Their Embryonic Persistence

Stem Cells International ◽

10.1155/2015/218518 ◽

2015 ◽

Vol 2015 ◽

pp. 1-13

Author(s):

Georg Kuales ◽

Matthias Weiss ◽

Oliver Sedelmeier ◽

Dietmar Pfeifer ◽

Sebastian J. Arnold

Keyword(s):

Stem Cells ◽

Expression Profiles ◽

Marker Genes ◽

Specific Marker ◽

Loss Of Function ◽

Trophoblast Stem Cells ◽

Transcriptional Signature ◽

Protein Levels ◽

Trophoblast Stem ◽

Bona Fide

Trophoblast stem cells (TSCs) represent the multipotent progenitors that give rise to the different cells of the embryonic portion of the placenta. Here, we analysed the expression of key TSC transcription factorsCdx2,Eomes, andElf5in the early developing placenta of mouse embryos and in cultured TSCs and reveal surprising heterogeneity in protein levels. We analysed persistence of TSCs in the early placenta and find that TSCs remain in the chorionic hinge until E9.5 and are lost shortly afterwards. To define the transcriptional signature of bona fide TSCs, we used inducible gain- and loss-of-function alleles ofEomesorCdx2, andEomesGFP, to manipulate and monitor the core maintenance factors of TSCs, followed by genome-wide expression profiling. Combinatorial analysis of resulting expression profiles allowed for defining novel TSC marker genes that might functionally contribute to the maintenance of the TSC state. Analyses by qRT-PCR andin situhybridisation validated novel TSC- and chorion-specific marker genes, such asBok/Mtd, Cldn26, Duox2, Duoxa2, Nr0b1, andSox21. Thus, these expression data provide a valuable resource for the transcriptional signature of bona fide and early differentiating TSCs and may contribute to an increased understanding of the transcriptional circuitries that maintain and/or establish stemness of TSCs.

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