Clinicopathological characteristics and molecular analysis of lung cancer associated with ciliated muconodular papillary tumor/bronchiolar adenoma

Abstract

Ciliated muconodular papillary tumor/bronchiolar adenoma (CMPT/BA) is a benign tumor with a high frequency of BRAF or EGFR mutations. It remains unclear whether CMPT/BA is associated with a speci c type of lung cancer. Thus, we studied the clinicopathological and genetic characteristics of cases with coexisting CMPT/BA and primary lung cancer to explore this relationship. Among 1945 patients with resected stage 0-III primary lung cancer between 2015-2018, we identi ed eight patients with concurrent CMPT/BA (lung cancer associated with CMPT/BA; LCCM). We compared the gene mutation status of each lesion according to the target sequence using macro-dissected formalin-xed para n-embedded specimens. Whole-exon sequencing (WES) was performed for six lung cancer cases. The LCCM cohort was male-dominant (male:female = 6:2); the median age was 72 years (range 66-81); and most were smokers (six smokers). The most common histological type corresponding to LCCM was adenocarcinoma; however, two squamous cell carcinomas and one small cell carcinoma were also detected. CMPT/BA lesions in LCCM showed a median size of 0.5 cm (range 0.3-1.1). The mutational test revealed no shared mutations between CMPT/BA and lung cancer, except for one invasive mucinous adenocarcinoma (IMA) harboring an HRAS mutation (I46N, c.137T > A). HRAS (I46N) is a rare variant, and all tumors showed an approximately 50% variant allele frequency, suggesting a single nucleotide polymorphism. Other driver gene alterations in lung cancer included EGFR (InDel, n = 2), BRAF (V600E) (n = 1), KRAS (n = 2), GNAS (n = 1), and TP53 (n = 2) mutations. BRAF (V600E) was the most frequent mutation in CMPT/BA. In contrast, lung cancer showed no speci c trend in driver gene mutations. In conclusion, our study revealed differences in the gene mutation pro les of CMPT/BA and lung cancer in coexisting cases, suggesting a mostly independent tumorigenesis of CMPT/BA from lung cancer, except for one IMA with a rare HRAS SNV.

Network pharmacology-based analysis on the key mechanisms of Yiguanjian acting on chronic hepatitis

“…Based on the RWR rankings, GNAS was identified as the most significant target for CH treatment with YGJ. GNAS is closely linked with various malignancies, such as liver cancer, colorectal cancer [ 36 ], lung cancer [ 37 ], and biliary tract cancer [ 38 ]. Within this research, we verified that YGJ reduced GNAS expression and inhibited STAT3 activation, thus reducing the inflammatory response.…”