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. 2022 Aug 26:13:945038.
doi: 10.3389/fphar.2022.945038. eCollection 2022.

Whole-exome sequencing and bioinformatics analysis of a case of non-alpha-fetoprotein-elevated lung hepatoid adenocarcinoma

Yao Yao  1 , Xiaojiao Guan  2 , Guangyao Bao  1 , Jie Liang  1 , Tian Li  3 , Xinwen Zhong  1
Affiliations

Whole-exome sequencing and bioinformatics analysis of a case of non-alpha-fetoprotein-elevated lung hepatoid adenocarcinoma

Yao Yao et al. Front Pharmacol. .

Abstract

Hepatoid adenocarcinoma of the lung (HAL) is an exceptionally rare malignant tumor with prominent hepatocellular carcinoma (HCC)-like characteristics in organs or tissues outside the liver, while there is no tumor in the liver. Most HAL cases have various degrees of serum alpha-fetoprotein (AFP) levels and exhibit a similar origin and clonal evolution process to HCC. We studied a case of HAL without elevating the AFP level by performing whole-exome sequencing (WES) and bioinformatics analyses after surgical resection. Our results showed mutations in two driver genes, NLRP3 and PBX1, and we identified HNRNPR, TP73, CFAP57, COL11A1, RUSC1, SLC6A9, DISC1, NBPF26, and OR10K1 as potential driver mutation genes in HAL. In addition, 76 significantly mutated genes (SMG) were identified after the statistical test of each mutation type on genes.

Keywords: alpha-fetoprotein; clinical research; hepatoid adenocarcinoma of the lung; lung cancer; whole-exome sequencing.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Chest CT images of the HAL patient. (A,B,C) CT images of the lung window with a lung mass in the left upper lobe. (D,E,F) CT images of the mediastinum window with a lung mass in the left upper lobe.
FIGURE 2
FIGURE 2
Hematoxylin-eosin staining on patient’s tumor tissue. (A) ( × 40, 200 µm), (B) ( × 100, 100 µm) Left side of the picture is the lung tissue, and alveolar fusion and inflammatory cell infiltration can be seen; the right side is a large tumor tissue, and fibrous tissue proliferation and inflammatory cell infiltration can be seen around the tumor tissue. (C) ( × 40, 300 µm), (D) ( × 100, 100 µm) Tumor tissue is distributed in the form of beams and nests, with abundant cytoplasm, similar to hepatocellular carcinoma.
FIGURE 3
FIGURE 3
Immunohistochemical and hematoxylin-eosin staining on patient’s tumor tissue ( × 40, 300 µm). (A) HE staining, (B) hepatocyte (+), (C) glypican-3 (+), (D) CK (+), (E) Ki-67 (30% +), (F) P40 (−), (G) P63 (−), (H) TTF-1 (−), and (I) napsin-A (−).
FIGURE 4
FIGURE 4
Genome location of SNVs and indels in tumor tissue. (A) Proportion of SNVs in different parts of the genome. (B) Proportion of indels in different parts of the genome.
FIGURE 5
FIGURE 5
Circle graph of somatic mutations found in tumor samples. Circle 1: outer frame of the chromosome; Circle 2: sequencing coverage map of tumor samples; Circle 3: sequencing coverage map of normal samples; Circle 4: green dots indicate the density of SNP indel; Circle 5: CNV results, red indicates the copy number increase; Circle 6: CNV results, blue indicates copy number deletion; we found that by comparing with paracancerous samples, the differential mutations in tumor samples were mainly located on chromosome 1.
FIGURE 6
FIGURE 6
General map of high-frequency mutations. Left: percentage of genetic mutations; right: high-frequency mutant gene significance; top: mutation frequency of samples; middle: mutation types, including I. missense (green), II. splicing (yellow), III. frameshift_in (purple), IV. frameshift_del (red), and V. nonsense.
FIGURE 7
FIGURE 7
KEGG and GO analyses of identified high-frequency mutant genes. Gene Ontology (A) biological process, (B) cellular component, and (C) molecular function; X-axis: the ratio of enriched genes to the total genes; Y-axis: GO terms. The dot size represents the number of enriched genes, and the color represents the p-value. (D) KEGG pathway analysis; X-axis: the ratio of enriched genes to the total genes; Y-axis: the terms of pathways. The dot size represents the number of enriched genes, and the Q-value is 0.784115.
FIGURE 8
FIGURE 8
Co-expression information between mutated NLRP3, PBX1, FAT1, EGFR, KRAS, and TP53 in HCC and LUAD tissues.
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