29-Gene Liver Cancer Subtype and Immunotherapy Effectiveness

Inclusion Criteria:

* ≥18 years old.
* Patients who visited multiple centers including Sir Run Run Shaw Hospital, Zhejiang University School of Medicine (the leading center) and were diagnosed with primary hepatocellular carcinoma by surgical pathological histology.
* They received targeted drug combined with immune checkpoint inhibitor treatment after the specimen collection time point (post - surgery or post - puncture) (that is: local treatments such as TACE, ablation, etc. are allowed before the start of targeted - immunotherapy combination treatment, but an interval of ≥4 weeks from the targeted - immunotherapy treatment is required).
* Had measurable tumor lesions at the observation start point (according to RECIST 1.1 criteria), and the tumor response status (including complete response \[CR\], partial response \[PR\], stable disease \[SD\] or progressive disease \[PD\]) could be judged by imaging examination during the observation (such as post - treatment evaluation).
* Had accessible frozen tumor tissue samples from surgical resection (sample volume ≥3g); or tumor tissue samples obtained by puncture (puncture samples need to meet the pathological diagnosis requirements, and the sample quality can support subsequent transcriptome sequencing and analysis).
* Voluntarily participate in this study and sign the informed consent form. If the subject is unable to read and sign the informed consent form due to incapacity and other reasons, their guardian shall act as the agent for the informed process and sign the informed consent form. If the subject is unable to read the informed consent form (e.g., illiterate subject), a witness shall witness the informed process and sign the informed consent form.

Exclusion Criteria:

* Received any local treatment during the targeted - immunotherapy combination treatment (including during treatment and within 4 weeks after treatment interruption), including:

Transcatheter arterial chemoembolization (TACE), transcatheter arterial embolization (TAE), drug - eluting bead transcatheter arterial chemoembolization (DEB - TACE) and other vascular interventional therapies; Radiofrequency ablation, microwave ablation, cryoablation, laser ablation and other ablation therapies; Stereotactic body radiation therapy (SBRT), three - dimensional conformal radiation therapy, intensity - modulated radiation therapy and other local radiation therapies; Intratumoral injection therapy, high - intensity focused ultrasound (HIFU) and other local physical/chemical therapies.

* Local treatment was initiated before the start of targeted - immunotherapy combination treatment, and the local treatment continued into the targeted - immunotherapy treatment period (that is, there was an overlap between local treatment and targeted - immunotherapy treatment or the interval was \< 4 weeks).
* Complicated with other active malignant tumors (except for those with cured basal cell carcinoma of the skin, carcinoma in situ of the cervix, and papillary thyroid carcinoma with no recurrence for more than 5 years after surgery).
* Severe impairment of important organ functions:

Liver function: Child - Pugh class C, or total bilirubin \> 3×ULN; Renal function: Serum creatinine \> 1.5×ULN and estimated glomerular filtration rate (eGFR) \< 50ml/min; Cardiac function: New York Heart Association (NYHA) cardiac function class Ⅲ - Ⅳ, or left ventricular ejection fraction (LVEF) \< 50%.

* Had uncontrolled active infections, including:

Hepatitis B virus DNA \> 2000IU/ml (without receiving antiviral treatment); Hepatitis C virus RNA positive and without receiving antiviral treatment; Active tuberculosis infection, septicemia, etc.

* Had a history of autoimmune diseases and currently still needed to use systemic glucocorticoids (prednisone \> 10mg/day) or other immunosuppressive therapies.
* Pregnant or lactating women, or patients planning to become pregnant during the study.
* Had a definite history of allergy to the targeted drugs or immune checkpoint inhibitors involved in the study.
* The researcher believed that there were other factors that might affect the judgment of treatment response (such as uncontrolled hypertension, coagulation dysfunction, simultaneous use of other antineoplastic drugs during targeted - immunotherapy treatment, etc.).