Inclusion Criteria:  1. Cohort 1 (young ESCC): aged 20 ~ 45 years old; Cohort 2 (reference-age ESCC): aged 46 ~ 74 years old); and Cohort 3 (elderly ESCC): aged 75 years or older.  2. Pathological reported as squamous cell carcinoma of the esophagus 3. Staged as clinical or pathological stage II to IVA in loco-regional ESCC group (per AJCC Cancer Staging System 8th edition); stage IVB in the metastatic group; or recurrent status (defined as disease recurrence occurring more than 6 months after curative chemoradiotherapy or surgery) in the recurrent group.  4. Willingness to provide archival or newly obtained tumor tissues for current study proposal.  5. Life expectancy more than 3 months. 6. Patients fully understand the protocol with the willingness to have regular follow-up.  6.2. Exclusion Criteria  Inability to cooperate by providing a complete medical history. No available tumor tissues for genetic testing. Undesirable compliance. Having a known additional malignancy that is progressing or has required active treatment within the past 3 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., cervical carcinoma in situ) that have undergone potentially curative therapy are not excluded.  Exclusion Criteria:  1. Inability to cooperate by providing a complete medical history. 2. No available tumor tissues for genetic testing. 3. Undesirable compliance. 4. Having a known additional malignancy that is progressing or has required active treatment within the past 3 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., cervical carcinoma in situ) that have undergone potentially curative therapy are not excluded.