Background Pancreatic cancer is the most aggressive malignancy of the digestive system, dominated by ductal adenocarcinoma. Although the incidence of pancreatic cancer is low compared to other tumors, its extremely low 5-year survival rate (less than 5%) makes pancreatic cancer the fourth leading cause of cancer-related mortality. For a long time, pathological diagnosis based on morphology has been the gold standard for pancreatic cancer diagnosis, but due to the high heterogeneity of tumors at the molecular level, the traditional pathological morphological diagnosis gradually fails to meet the developmental needs of pancreatic cancer research with the development of molecular diagnostic techniques in China and abroad. Therefore, the in-depth development of molecular typing of pancreatic cancer on the basis of the original pathological histological diagnosis is of great significance for the diagnosis, prognosis and treatment of pancreatic cancer. Research progress The molecular staging of tumors was first proposed by the National Cancer Institute in 1999 as a way to shift the classification of tumors from morphology to a tumor classification system based on molecular characteristics through comprehensive molecular analysis techniques. With this idea, molecular typing studies with differences in expression in different tumors at the level of DNA, RNA and protein molecules have been widely carried out. In recent years, due to the deepening of pancreatic cancer genetics research and the continuous improvement of high-throughput sequencing technology, the study of molecular typing of pancreatic cancer has also been developed continuously; a large number of comprehensive studies on pancreatic cancer genome sequencing and reports on genetic abnormalities of pancreatic cancer have been published in foreign authoritative scientific journals. The most representative one is that in 2008, the American journal Science reported that Professor Jones and his team detected exons in 24 cases of pancreatic ductal adenocarcinoma by polymerase chain reaction amplification and Sanger sequencing, and performed exon sequencing in another 90 cases of pancreatic cancer. The exon sequencing was validated in 90 additional pancreatic cancer samples. The study found that an average of 48 nonsilent mutations occurred in each pancreatic cancer sample, and these mutations were involved in 12 core signaling pathways. Among these mutations, the four “driver” genes of pancreatic cancer were recognized: oncogene KRAS, oncogene TP53, CDKN2A/p16 and SMAD4. The mutation rate of KRAS in pancreatic cancer is greater than 95%, CDKN2A/p16, and SMAD4 is greater than 90%, TP53 is 50%-75%, and SMAD4 is 55%, so it is also known as four “high-frequency driver genes”. In addition, seven other low-frequency driver genes: SMARC4A, CDH1, EPHA3, FBXW7, EGFR, IDH1 and NF1 are also involved in forming a genetic “topography” of pancreatic cancer. This “topography” is of great importance for the diagnosis, prognosis and individualized treatment of pancreatic cancer. Clinical implications It is currently believed that KRAS mutation is the earliest evidence of genetic alteration in pancreatic cancer development; SMAD4/DPC4 deletion is closely related to its prognosis after surgical resection; patients with DPC4 deletion have poorer prognosis, and immunolabeling of DPC4 protein can assist in the diagnosis of pancreatic cancer metastases (e.g. ovarian) originating from the pancreas rather than the primary cancer of the ovary. In addition, unlike SMAD4/DPC4 mutations, mutations in TP53 or CDKN2A /p16 alone do not predict survival in pancreatic cancer patients, but are as important as KRAS for pancreatic carcinogenesis. And the evolutionary progression from pancreatic pre-cancerous lesions to pancreatic cancer can be indirectly reflected according to the mutation of each gene: pancreatic intraepithelial neoplasia (PanIN) as an important pancreatic pre-cancerous lesion is classified into 3 grades (PanIN-1 to PanIN-3). the incidence of KRAS mutation in PanIN-1 is about 45%. Genetic alterations can indirectly reflect the aggressiveness and progression of pancreatic cancer, and therefore pancreatic cancer is considered to be the result of accumulation of genetic lesions. A study of pancreatic cancer-bearing families confirmed this view, finding that non-invasive precancerous lesions gradually increased with the accumulation of KRAS, CDKN2A/ p16, GNAS, TP53 and SMAD4 mutations, and progressed to pancreatic cancer outbreak. Meanwhile, the largest autopsy report of pancreatic cancer patients so far (76 cases) confirmed extensive metastasis in about 70% of patients, and inactive mutations in the SMAD4 gene were present in 70% of these pancreatic cancer patients, suggesting that potential alterations in SMAD4 are closely related to the progression and metastasis of pancreatic cancer. Therefore, different mutations play different roles in pancreatic cancer progression and are associated with the progression stage, so the identification of pancreatic cancer mutations provides potential therapeutic targets for pancreatic cancer individualization: for example, pancreatic cancer patients with confirmed BRCA2 or PALB2 mutations can preferentially receive PARP inhibitors or DNA cross-linking agents to control the disease. In conclusion, in-depth exploration of pancreatic cancer-related genomic, proteomic, and metabolomic analyses, construction of a complete molecular typing model for pancreatic cancer, and detailed pathological histological examination provide an important basis for heterogeneity, staging, diagnosis and prognosis, and individualized treatment of pancreatic cancer. Different treatment strategies will be adopted for different individual tumors or different stages of the same individual tumor to reasonably adjust the efficacy and reduce ineffective treatment, ultimately achieving the purpose of prolonging patient survival and improving quality of life.