The panoramic picture of pepsinogen gene family with pan‐cancer

Abstract

Background It is well known that pepsinogen (PGs), as an important precursor of pepsin performing digestive function, has a good correlation with the occurrence and development of gastric cancer and it is also known that ectopic PGs expression is related to the prognosis of some cancers. However, the panoramic picture of pepsinogen gene family in human cancer is not clear. This study focused on elucidating the expression profile, activated pathway, immune cells infiltration, mutation, and copy number variation of PGs and their potential role in human cancer. Method Based on the next generation sequence data from TCGA, Oncomine, and CCLE, the molecular changes and clinical correlation of PGs in 33 tumor types were analyzed systematically by R language, including the expression, mutation, and copy number variation of PGs and their correlation with cancer‐related signal transduction pathway, immune cell infiltration, and prognostic potential in different cancers. Results PGs expression profiles appear different in 33 tumors. The transcriptional expression of PGs was detected in 16 of all 33 tumors. PGC was highly expressed in cholangiocarcinoma, colon adenocarcinoma, rectum adenocarcinoma, uterine corpus endometrial carcinoma, bladder urothelial carcinoma and breast cancer, while decreased in stomach adenocarcinoma, kidney renal clear cell carcinoma, prostate adenocarcinoma, lung squamous cell carcinoma, and esophageal carcinoma. PGA3, PGA4, and PGA5 were expressed in most normal tissues, but decreased in cancer tissues. PGs expression was significantly related to the activation or inhibition of many signal transduction pathways, in which PGC and PGA5 are more likely to be associated with cancer‐related pathways. PGC participated in 33 regulatory network pathways in pan‐cancer, mainly distributed in stomach adenocarcinoma, esophageal carcinoma, and lung squamous cell carcinoma, respectively. PGC and PGA3 expression were significantly correlated with immune cell infiltration. The results of survival analysis showed that different PGs expression play significantly different prognostic roles in different cancers. PGC was correlated with poor survival in brain lower grade glioma, skin cutaneous melanoma, and higher survival in kidney renal clear cell carcinoma, acute myeloid leukemia, mesothelioma, and uveal melanoma. PGA4 was only associated with higher survival in kidney renal clear cell carcinoma. Genetic variation analysis showed that PGC gene often mutated in uterine corpus endometrial carcinoma and stomach adenocarcinoma had extensive copy number amplification in various tumor types. PGC expression was upregulated with the increase of copy number in cholangiocarcinoma, esophageal carcinoma, and kidney renal papillary cell carcinoma, while in stomach adenocarcinoma, PGC was upregulated regardless of whether the copy number was increased or decreased. Conclusions PGs was expressed unevenly in ...

Multimolecular Characteristics and Role of BRCA1 Interacting Protein C-Terminal Helicase 1 (BRIP1) in Human Tumors: A Pan-Cancer Analysis

“…However, the role of BRIP1 in the pathogenesis of various cancers remains to be illuminated. Pan-cancer studies have recently emerged as a novel perspective for understanding the molecular mechanisms of tumorigenesis and development of human cancers (29)(30)(31)(32)(33)(34)(35), and we failed to obtain the pan-cancer analysis of BRIP1 across human tumors from literature search. Therefore, we used the multilevel data of human databases to analyze the expression, prognostic potential, mutation, methylation, genomic characteristics, activation or inhabitation of cancer-related pathways, and immune in ltration of BRIP1 gene in 33 TCGA tumors, aimed to gure out the multimolecular characteristics and role of BRIP1 in the carcinogenesis, development, and prognosis of tumors.…”

Gastroprotective Mechanisms

“…It is produced by the main cells from the inactive form "pepsinogen" stored in zymogen granules. Under physiological or chemical signals, these granules secrete pepsinogen into the gastric cavity, where is activated into pepsin in the presence of HCl from the gastric juice [24,28,29]. The main cells secrete pepsin in its inactive form that prevents the self-digestion of protective proteins in the lining of the gastrointestinal tract.…”

“…There are two types of pepsinogens, type A (with three subtypes A3, A4, and A5) and type C [28,29]. Other authors refer to pepsinogen as type I and type II.…”

“…Pepsinogen type A can be used as a diagnostic biomarker for chronic atrophic gastritis and gastric neoplasms [33], and type C pepsinogen as a biomarker for prediction, diagnosis, and prognosis of different types of cancer because it has a broad-spectrum expression characteristic [28].…”

“…The basic components of mucus are mucin glycoproteins (such as Muc5AC, Muc1, and MUC6) and lectins such as trefoil factor (TFF) 1 and 2 and Griffonia simplicifolia II (GSA-II), which bind to MUC6 and stabilize gastric mucus [38,[47][48][49][50]. It is noteworthy that mucins are mainly responsible for the viscous character of mucus and TFFs are typical constituents of mucus-secreting epithelia [28,50,51]. In gastric neoplasms with differentiation of the oxyntic glands, immature MUC6 is produced from the pyloric gland, with an absence of α1,4-linked N-acetylglucosamines glycosylation [52], MUC6 positive immunostaining occurs in gastric adenocarcinoma of the fundic gland [34] and MUC5AC/MUC6 positive immunostaining for honeycomb gastric cancer [35].…”