Yu Zheng1, Yifeng Sun2, Yue Kuai1, Guoxiang Fu3, Huimin An3, Jinyun Chen4, Jinying Chen2, Jiajun Zhu2, Yixin Wo2, Yiwang Wu2, Kaibin Song2, Qinghua Xu5,6, Di Wu7, Deshuang Huang7, Qifeng Wang8,9, Hongming Pan10,11. 1. Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, East Qinchun Road 3, Hangzhou, 310016, Zhejiang, China. 2. Canhelp Genomics Research Center, Xinyan Road 22, Hangzhou, 311100, Zhejiang, China. 3. Department of Pathology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China. 4. Department of General Surgery, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China. 5. Canhelp Genomics Research Center, Xinyan Road 22, Hangzhou, 311100, Zhejiang, China. qinghua.xu@cancerhelp.cn. 6. Institute of Machine Learning and Systems Biology, College of Electronics and Information Engineering, Tongji University, Shanghai, China. qinghua.xu@cancerhelp.cn. 7. Institute of Machine Learning and Systems Biology, College of Electronics and Information Engineering, Tongji University, Shanghai, China. 8. Department of Pathology, Fudan University Shanghai Cancer Center, Dong'An Road 270, Shanghai, 200032, China. Wangwangqifeng19821982@126.com. 9. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. Wangwangqifeng19821982@126.com. 10. Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, East Qinchun Road 3, Hangzhou, 310016, Zhejiang, China. panhongming@zju.edu.cn. 11. Laboratory of Cancer Biology, Institute of Clinical Science, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China. panhongming@zju.edu.cn.
Abstract
BACKGROUND: The incidence of multiple primary malignant tumors (MPMTs) is rising due to the development of screening technologies, significant treatment advances and increased aging of the population. For patients with a prior cancer history, identifying the tumor origin of the second malignant lesion has important prognostic and therapeutic implications and still represents a difficult problem in clinical practice. METHODS: In this study, we evaluated the performance of a 90-gene expression assay and explored its potential diagnostic utility for MPMTs across a broad spectrum of tumor types. Thirty-five MPMT patients from Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University and Fudan University Shanghai Cancer Center were enrolled; 73 MPMT specimens met all quality control criteria and were analyzed by the 90-gene expression assay. RESULTS: For each clinical specimen, the tumor type predicted by the 90-gene expression assay was compared with its pathological diagnosis, with an overall accuracy of 93.2% (68 of 73, 95% confidence interval 0.84-0.97). For histopathological subgroup analysis, the 90-gene expression assay achieved an overall accuracy of 95.0% (38 of 40; 95% CI 0.82-0.99) for well-moderately differentiated tumors and 92.0% (23 of 25; 95% CI 0.82-0.99) for poorly or undifferentiated tumors, with no statistically significant difference (p-value > 0.5). For squamous cell carcinoma specimens, the overall accuracy of gene expression assay also reached 87.5% (7 of 8; 95% CI 0.47-0.99) for identifying the tumor origins. CONCLUSIONS: The 90-gene expression assay provides flexibility and accuracy in identifying the tumor origin of MPMTs. Future incorporation of the 90-gene expression assay in pathological diagnosis will assist oncologists in applying precise treatments, leading to improved care and outcomes for MPMT patients.
BACKGROUND: The incidence of multiple primary malignant tumors (MPMTs) is rising due to the development of screening technologies, significant treatment advances and increased aging of the population. For patients with a prior cancer history, identifying the tumor origin of the second malignant lesion has important prognostic and therapeutic implications and still represents a difficult problem in clinical practice. METHODS: In this study, we evaluated the performance of a 90-gene expression assay and explored its potential diagnostic utility for MPMTs across a broad spectrum of tumor types. Thirty-five MPMT patients from Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University and Fudan University Shanghai Cancer Center were enrolled; 73 MPMT specimens met all quality control criteria and were analyzed by the 90-gene expression assay. RESULTS: For each clinical specimen, the tumor type predicted by the 90-gene expression assay was compared with its pathological diagnosis, with an overall accuracy of 93.2% (68 of 73, 95% confidence interval 0.84-0.97). For histopathological subgroup analysis, the 90-gene expression assay achieved an overall accuracy of 95.0% (38 of 40; 95% CI 0.82-0.99) for well-moderately differentiated tumors and 92.0% (23 of 25; 95% CI 0.82-0.99) for poorly or undifferentiated tumors, with no statistically significant difference (p-value > 0.5). For squamous cell carcinoma specimens, the overall accuracy of gene expression assay also reached 87.5% (7 of 8; 95% CI 0.47-0.99) for identifying the tumor origins. CONCLUSIONS: The 90-gene expression assay provides flexibility and accuracy in identifying the tumor origin of MPMTs. Future incorporation of the 90-gene expression assay in pathological diagnosis will assist oncologists in applying precise treatments, leading to improved care and outcomes for MPMT patients.