A Pan-cancer Analysis On Clinic And Genomic Characteristic Of Multiple Primary Cancers Based On TCGA Database

ObjectivesMultiple primaries are defined as more than one synchronous or metachronous cancer in the same individual.Currently,the incidence of multiple primary cancer increases year by year.The purpose of this study is to summarize the clinical characteristics of multiple primary cancers through the clinical and large-scale sequencing results in the TCGA database,in order to find the basis for the prevention and improvement of the prognosis of multiple primary cancers,and to find possible potential therapeutic means by summarizing the characteristics of genomics.MethodsThe 11,000 patients in the TCGA database with all types of cancer were divided into patients with multiple primary cancers and patients without multiple primary cancers according to the patients’ history of other malignancy.The distribution characteristics of cancer types in patients with multiple primary tumors were analyzed,and the differences in age,gender,race and pathological stage between multiple primary cancers and non-multiple primary cancers were compared.The prognosis of multiple primary cancers was compared with that of non-multiple primary cancers,and the possible confounding factors affecting the prognosis such as tumor type,age,gender and stage were analyzed.We proposed a hypothesis that patients with multiple primary cancers may have a higher tumor mutation burden.The genomic data of TCGA were used to compare the difference of mutation burden between multiple primary cancers and non-multiple primary cancers,so as to find possible predictors of immunotherapy.Clinical data of multiple primary cancers in our canter were collected to supplement the missing information in the TCGA database.Results1.Age is the most important risk factor for patients with multiple primary tumors,but genetic changes related to hereditary tumor syndrome may play a more important role in some certain types of cancers.2.The early diagnosis rate of the second primary cancer in patients with multiple primary cancers is higher than that in the general population,but this part of the difference may not be caused by closer follow-up screening in patients with multiple primary cancers,but is related to the disease characteristic of the multiple primary cancers themselves.3.For the metachronous multiple primary cancers of the pan-cancer cohort,after the occurrence of the second primary cancer,the prognosis of the patient is only related to the patient’s age,the type and stage of the second primary cancer,and has nothing to do with the first primary cancer.However,for some certain types of cancer,especially for patients whose second primary cancer is thyroid cancer,the prognosis of patients is mainly affected by the first primary cancer.4.In tumors with high mutation burden,previous malignant tumor history is a protective factor for overall survival,while in tumors with low mutation burden,previous malignant tumor history is a risk factor for overall survival.5.The tumor mutation burden(TMB)of multiple primary cancers was significantly higher than that of non-multiple primary cancers,especially in patients with cutaneous melanoma and esophageal cancer,and the difference was significant enough to predict the efficacy of immunotherapy only based on the patient’s previous history of malignant cancers.This makes it possible that the history of other cancers in the past may be the most readily available predictor of immunotherapy in some certain type of cancers.