Increased Prevalence of Alpha-1-Antitrypsin Deficiency in Patients with Biliary Tract Cancer and Its Associated Clinicopathological Features

Abstract

Alpha-1 antitrypsin deficiency (A1ATD) is underdiagnosed and associated with liver diseases. Here, we genotyped 130 patients with biliary tract cancer (BTC) scheduled for liver resection and found A1ATD in 10.8% of the patients. A1ATD was found in all BTC subtypes, and patients had similar clinical features as non-A1ATD BTC, not permitting their identification using clinical routine liver tests. In intrahepatic cholangiocarcinoma (iCCA), the abundance of A1AT protein was increased in the tumor and appeared to be influenced by the genomic alterations. On the one hand, BTC with A1ATD had lower perineural invasion at histopathology and displayed a longer survival, suggesting that a deficiency in this protein is associated with a less aggressive phenotype. On the other hand, iCCA with high A1AT expression had more advanced tumor staging and enriched pathways for complement system and extracellular matrix interactions, indicating that A1AT protein might contribute to a more aggressive phenotype. With increased awareness, screening, and basic studies, A1ATD could represent one more layer of stratification for future targeted therapies in BTC.

Retro-Inverso Collagen Modulator Peptide Derived from Serpin A1 with Enhanced Stability and Activity In Vitro

“…This should be considered an added value in the design of new cosmeceutical ingredients, whose claims are rarely supported by appropriate studies but rather anecdotally reported. In addition to the cosmeceutical application, evidence on the implication of neutrophil serine proteases (NSPs) such as elastase, proteinase 3 (PR3), cathepsin G (CatG), and matrix metalloproteases (MMPs) as pathogenic determinants of chronic inflammatory lung disorders that are associated with increased protease activity suggest potential interest of a further investigation of the use of short sequences derived from serpin A1 for pharmaceutical applications. , Moreover, another possible application to be investigated is the use of this peptide to compensate for α-1-antitrypsin deficiency (A1TD), which is an under-diagnosed pathology associated with chronic obstructive pulmonary disease (COPD) and chronic liver diseases. − …”

Perineural invasion confers poorer clinical outcomes in patients with T1/T2 intrahepatic cholangiocarcinoma: a single center, retrospective cohort study

“…Furthermore, PNI may serve as a substitute for biological markers of invasive disorders that reflect tumor or stage-specific characteristics substantially. In PNI-positive ICC patients, molecules associated with a poorer prognosis for ICC, such as NPY1R , A1ATD , GPX4 , and KRAS mutations, exhibit elevated levels ( 33 - 36 ). Future research should focus on elucidating the molecular mechanism behind tumor-nerve interactions and PNI-related carcinogenesis.…”