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 ch...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2019-11-01
|
| Series: | BMC Genomics |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12864-019-6086-2 |
| _version_ | 1818558165718925312 |
|---|---|
| author | Xin Li Gengen Shi Qingsong Chu Wenbin Jiang Yixin Liu Sainan Zhang Zheyang Zhang Zixin Wei Fei He Zheng Guo Lishuang Qi |
| author_facet | Xin Li Gengen Shi Qingsong Chu Wenbin Jiang Yixin Liu Sainan Zhang Zheyang Zhang Zixin Wei Fei He Zheng Guo Lishuang Qi |
| author_sort | Xin Li |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T00:09:10Z |
| format | Article |
| id | doaj.art-10413f4adcb24ec1ae4ee1a30f75773e |
| institution | Directory Open Access Journal |
| issn | 1471-2164 |
| language | English |
| last_indexed | 2024-12-14T00:09:10Z |
| publishDate | 2019-11-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Genomics |
| spelling | doaj.art-10413f4adcb24ec1ae4ee1a30f75773e2022-12-21T23:25:50ZengBMCBMC Genomics1471-21642019-11-0120111610.1186/s12864-019-6086-2A qualitative transcriptional signature for the histological reclassification of lung squamous cell carcinomas and adenocarcinomasXin Li0Gengen Shi1Qingsong Chu2Wenbin Jiang3Yixin Liu4Sainan Zhang5Zheyang Zhang6Zixin Wei7Fei He8Zheng Guo9Lishuang Qi10College of Bioinformatics Science and Technology, Harbin Medical UniversityCollege of Bioinformatics Science and Technology, Harbin Medical UniversityFujian Key Laboratory for Translational Research, Institute of Translational Medicine, Fujian Medical UniversityCollege of Bioinformatics Science and Technology, Harbin Medical UniversityCollege of Bioinformatics Science and Technology, Harbin Medical UniversityCollege of Bioinformatics Science and Technology, Harbin Medical UniversityCollege of Bioinformatics Science and Technology, Harbin Medical UniversityDepartment of Medical Oncology, Harbin Medical University Cancer hospitalKey Laboratory of Ministry of Education for Gastrointestinal Cancer, Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical UniversityCollege of Bioinformatics Science and Technology, Harbin Medical UniversityCollege of Bioinformatics Science and Technology, Harbin Medical UniversityAbstract 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.http://link.springer.com/article/10.1186/s12864-019-6086-2Non-small cell lung cancerHistological subtypePathological assessmentRelative gene expression orderingsQualitative transcriptional signature |
| spellingShingle | Xin Li Gengen Shi Qingsong Chu Wenbin Jiang Yixin Liu Sainan Zhang Zheyang Zhang Zixin Wei Fei He Zheng Guo Lishuang Qi A qualitative transcriptional signature for the histological reclassification of lung squamous cell carcinomas and adenocarcinomas BMC Genomics Non-small cell lung cancer Histological subtype Pathological assessment Relative gene expression orderings Qualitative transcriptional signature |
| title | A qualitative transcriptional signature for the histological reclassification of lung squamous cell carcinomas and adenocarcinomas |
| title_full | A qualitative transcriptional signature for the histological reclassification of lung squamous cell carcinomas and adenocarcinomas |
| title_fullStr | A qualitative transcriptional signature for the histological reclassification of lung squamous cell carcinomas and adenocarcinomas |
| title_full_unstemmed | A qualitative transcriptional signature for the histological reclassification of lung squamous cell carcinomas and adenocarcinomas |
| title_short | A qualitative transcriptional signature for the histological reclassification of lung squamous cell carcinomas and adenocarcinomas |
| title_sort | qualitative transcriptional signature for the histological reclassification of lung squamous cell carcinomas and adenocarcinomas |
| topic | Non-small cell lung cancer Histological subtype Pathological assessment Relative gene expression orderings Qualitative transcriptional signature |
| url | http://link.springer.com/article/10.1186/s12864-019-6086-2 |
| work_keys_str_mv | AT xinli aqualitativetranscriptionalsignatureforthehistologicalreclassificationoflungsquamouscellcarcinomasandadenocarcinomas AT gengenshi aqualitativetranscriptionalsignatureforthehistologicalreclassificationoflungsquamouscellcarcinomasandadenocarcinomas AT qingsongchu aqualitativetranscriptionalsignatureforthehistologicalreclassificationoflungsquamouscellcarcinomasandadenocarcinomas AT wenbinjiang aqualitativetranscriptionalsignatureforthehistologicalreclassificationoflungsquamouscellcarcinomasandadenocarcinomas AT yixinliu aqualitativetranscriptionalsignatureforthehistologicalreclassificationoflungsquamouscellcarcinomasandadenocarcinomas AT sainanzhang aqualitativetranscriptionalsignatureforthehistologicalreclassificationoflungsquamouscellcarcinomasandadenocarcinomas AT zheyangzhang aqualitativetranscriptionalsignatureforthehistologicalreclassificationoflungsquamouscellcarcinomasandadenocarcinomas AT zixinwei aqualitativetranscriptionalsignatureforthehistologicalreclassificationoflungsquamouscellcarcinomasandadenocarcinomas AT feihe aqualitativetranscriptionalsignatureforthehistologicalreclassificationoflungsquamouscellcarcinomasandadenocarcinomas AT zhengguo aqualitativetranscriptionalsignatureforthehistologicalreclassificationoflungsquamouscellcarcinomasandadenocarcinomas AT lishuangqi aqualitativetranscriptionalsignatureforthehistologicalreclassificationoflungsquamouscellcarcinomasandadenocarcinomas AT xinli qualitativetranscriptionalsignatureforthehistologicalreclassificationoflungsquamouscellcarcinomasandadenocarcinomas AT gengenshi qualitativetranscriptionalsignatureforthehistologicalreclassificationoflungsquamouscellcarcinomasandadenocarcinomas AT qingsongchu qualitativetranscriptionalsignatureforthehistologicalreclassificationoflungsquamouscellcarcinomasandadenocarcinomas AT wenbinjiang qualitativetranscriptionalsignatureforthehistologicalreclassificationoflungsquamouscellcarcinomasandadenocarcinomas AT yixinliu qualitativetranscriptionalsignatureforthehistologicalreclassificationoflungsquamouscellcarcinomasandadenocarcinomas AT sainanzhang qualitativetranscriptionalsignatureforthehistologicalreclassificationoflungsquamouscellcarcinomasandadenocarcinomas AT zheyangzhang qualitativetranscriptionalsignatureforthehistologicalreclassificationoflungsquamouscellcarcinomasandadenocarcinomas AT zixinwei qualitativetranscriptionalsignatureforthehistologicalreclassificationoflungsquamouscellcarcinomasandadenocarcinomas AT feihe qualitativetranscriptionalsignatureforthehistologicalreclassificationoflungsquamouscellcarcinomasandadenocarcinomas AT zhengguo qualitativetranscriptionalsignatureforthehistologicalreclassificationoflungsquamouscellcarcinomasandadenocarcinomas AT lishuangqi qualitativetranscriptionalsignatureforthehistologicalreclassificationoflungsquamouscellcarcinomasandadenocarcinomas |