Granted Patent B2

US 12,297,505 · App. 17/218,127 · Granted May 13, 2025

Inventors: Duncan H. Whitney (Boston, MA); Michael Elashoff (Redwood City, CA)

Assignee: Veracyte, Inc.

C12Q1/6886G01N33/57407G06N20/00G16B40/00G16H50/20C12Q2600/112C12Q2600/158G16B25/00

Abstract

Claims (35)

1. A method, comprising:

(a) performing an imaging analysis on a subject to detect a presence of a pulmonary nodule in said subject, wherein said imaging analysis comprises computer-aided tomography, magnetic resonance imaging, ultrasonography, or chest X-ray;

(b) determining, based at least in part on said imaging analysis, that said pulmonary nodule is indeterminate for indicating a presence of lung cancer in said subject or an absence of lung cancer in said subject;

(c) responsive to said determining that said pulmonary nodule is indeterminate, obtaining a nasal sample from a nose of said subject, wherein said subject is suspected of having lung cancer based at least in part on said imaging analysis of said subject;

(d) assaying messenger ribonucleic acid (mRNA) molecules from said nasal sample to determine a plurality of gene expression levels in said nasal sample,

wherein said plurality of gene expression levels comprises at least one gene expression level of a gene that correlates with self-reportable characteristics of said subject and at least one gene expression level of an informative gene that is differentially expressed in subjects with lung cancer as compared to subjects without lung cancer;

(e) processing said plurality of gene expression levels to determine that said pulmonary nodule is associated with or is likely to be associated with presence of said lung cancer in said subject,

wherein said processing comprises weighting said at least one gene expression level that correlates with said self-reportable characteristics of said subject by its relative contribution to said determining in (e),

wherein said self-reportable characteristics comprise two or more members selected from the group consisting of smoking status, age, and gender; and

(f) responsive to said determining in (e), administering a treatment to said subject thereby treating said subject for said lung cancer,

wherein said treatment is selected from the group consisting of surgical resection, chemotherapy, chemoradiation, stereotactic body radiotherapy, and radiofrequency ablation.

2. The method of claim 1 , wherein said lung cancer is adenocarcinoma, squamous cell carcinoma, small cell lung cancer, or non-small cell lung cancer.

3. The method of claim 1 , wherein (e) further comprises determining a lung cancer risk of said subject by applying a model to said plurality of gene expression levels.

4. The method of claim 3 , wherein said lung cancer risk is determined using a combination of weighted expression levels.

5. The method of claim 4 , wherein said weighted expression levels are weighted by a relative contribution to predicting an increased likelihood of having said lung cancer.

6. The method of claim 3 , wherein said model has a Negative Predictive Value (NPV) of greater than 90% for ruling out said lung cancer.

7. The method of claim 3 , wherein said model has a Negative Predictive Value (NPV) of greater than 85% for ruling out said lung cancer in subjects diagnosed with chronic obstructive pulmonary disease (COPD).

8. The method of claim 1 , further comprising, responsive to said determining in (e), performing an invasive lung procedure on said subject for detecting said lung cancer in said subject.

9. The method of claim 8 , wherein said invasive lung procedure is selected from the group consisting of a bronchoscopy, a transthoracic needle aspiration, a transthoracic needle biopsy (TTNB), a surgical lung biopsy (SLB), a mediastinoscopy, a thoracoscopy, a thoracotomy, and a video-assisted thoracoscopic surgery (VATS).

10. The method of claim 9 , wherein said invasive lung procedure is said bronchoscopy.

11. The method of claim 1 , wherein said assaying comprises use of at least one nucleic acid probe that specifically hybridizes with a messenger ribonucleic acid molecule in said nasal sample.

12. The method of claim 11 , wherein said at least one nucleic acid probe is immobilized on a solid support.

13. The method of claim 1 , wherein said processing comprises comparing said plurality of gene expression levels to a reference level.

14. The method of claim 1 , wherein said subject is suspected of having lung cancer based at least in part on said subject exhibiting one or more symptoms of said lung cancer.

15. The method of claim 14 , wherein said one or more symptoms of said lung cancer comprise a persistent cough, worsening of an existing cough, blood in sputum of said subject, persistent bronchitis, chest pain, unexplained weight loss, shortness of breath, or wheezing.

16. The method of claim 1 , wherein said assaying comprises performing hybridization on said nasal sample using at least one probe for said gene that relates to said one or more self-reportable characteristics of said subject.

17. The method of claim 1 , further comprising repeating (c) to (e) within six months.

18. The method of claim 1 , wherein said subject is asymptomatic for said lung cancer.

19. The method of claim 1 , wherein said nasal sample comprises respiratory epithelium of said nose of said subject.

20. The method of claim 1 , wherein said informative gene is selected from the group consisting of: TMEM51, CRIL, PDZK1IP 1, MICAL2, VWA5A, ACAD8, SAA4, GLYATL2, ETV6, CD177, CEACAM7, CD177, QPCT, CASP10, PI3, BST1, MTNRIA, STARD4, CFB, SLC26A8, VNN2, HDAC9, SLC26A4, LCN2, CFB, CCDC18, FAM72D, NUF2, FAM72D, FBXO28, GPR137B, STIL, DEPDCI, TSPAN2, FAM72D, ASPM, KIF14, KIF20B, RAD51AP1, GAS2L3, SPIC, SMAGP, ATP12A, BRCA2, BORA, SKA3, DLGAP5, CASC5, LRRC28, PYCARD, TXNL4B, EFCAB5, SPAG5, FAM72D, ABCA12, AURKA, SGOL1, BANKI, CENPE, CASP6, MAD2L1, CCNA2, CCNB1, KIF20A, CENPK, ERAP1, FAM54A, PHTF2, CLDN12, BPGM, PCMTD1, MELK, MST4, CR1, GOS2, CSF3R, S100A12, SELL, NCF2, LIPN, ZNF438, NAMPT, CBL, CASP5, CARD16, CARD17, CLEC4A, LRRK2, HMGN2P46, AQP9, BCL2A1, ITGAX, GPR97, CCL4, PSTPIP2, IFI30, FFAR2, EMR3, FPRI, LILRA5, PLEK, MXDI, TNFAIP6, CXCR2, IL1B, CXCR1, SIRPB1, NCF4, IRAK2, PROK2, TLR2, TREM1, SOD2, CREB 5, NAMPT, TNFRSF10C, CSGALNACT1, ASAP1, PLA2G2A, NFYC, RASSF10, GLB1L3, TRIM3, MCAM, MSRB3, SLITRK5, GAS6, NOVA1, GABRG3, ABCA3, LPO, FSCN2, RASD1, HILS1, SDK2, NTN5, KCNA7, ATOH8, KCNIP3, INHBB, VSTM2L, ZNRF3, PLEKHG4B, GNMT, GABBR1, ARHGEF10, SDC2, CRB2, GAS1, PNPLA7, RAI2, PLA2G2A, ID3, PGLYRP4, SFTPA1, SFTPA1, LIPK, SFTPA2, SFTPA2, ASCL3, RPPH1, CD209, GPR32, UGT2A3, CD58, LBR, ARHGDIB, SLC12A6, LPCAT2, PLEKHB2, KYNU, ANKRD36B, ANKRD36B, ANKRD36B, SRD5A3, NEIL3, TLR1, BCAP29, MGAM, TPK1, ATP6V1B2, LYN, SDCBP, GK, GLA, ADRA2A, PRKCDBP, PRR4, PRB4, PRB3, PRB1, PRB2, BMP4, PRKCA, CYP1B1-AS1, CGREF1, RPRM, SDPR, BPIFB2, BPIFB 6, SNCA, CLDN22, COBL, NKX3-1, CDR1, CH25H, FXCI, DLG2, NRXN3, CES1P1, CES1, KCNJ16, APCDD1, TMEM178, MYRIP, FLNB, ENPP5, SEMA3E, SLC7A2, ARHGAP6, ANO3, SLC22A10, UFM1, EPHX3, KLF7, LGSN, LYPD2, CES3, MIA, RNF150, SLC9A3, and MYOT.

21. The method of claim 1 , wherein said treatment is said surgical resection.

22. The method of claim 1 , wherein said treatment is said chemotherapy.

23. The method of claim 1 , wherein said treatment is said chemoradiation.

24. The method of claim 1 , wherein said treatment is said stereotactic body radiotherapy.

25. The method of claim 1 , wherein said treatment is said radiofrequency ablation.

Assignments (2)

Continuity (6)

References Cited (400)